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Biomedical subjects

R Lim

Publications and source records attributed to R Lim.

At least 37 records · Page 2Linked to original sources
PubMed1999

Quantal size is correlated with receptor cluster area at glycinergic synapses in the rat brainstem.

1. Whole-cell patch electrode recordings of glycinergic miniature inhibitory postsynaptic currents (mIPSCs) were obtained in neurons of the rat anteroventral cochlear nucleus (AVCN). Mean mIPSC peak amplitude was found to vary considerably between AVCN neurons (range, -19.1 to -317.9 pA; mean +/- s.d., -159.1 +/- 100.7 pA; 14 cells). 2. Immunolabelling of glycinergic receptor clusters in AVCN neurons was performed using antibodies against the glycine receptor clustering protein gephyrin. Measurements of the area of gephyrin immunoreactive clusters were obtained using confocal fluorescence microscopy. These measurements showed a large variability in cluster area, not only in the same cell (mean coefficient of variation, c.v., 0.66 +/- 0.18; 16 cells), but also in mean cluster area between cells (range, 0.21-0.84 microm2; 16 cells). 3. A possible relationship between mIPSC amplitude and receptor cluster area was investigated in a further series of experiments, in which mIPSCs recordings and immunolabelling of glycine receptor clusters were obtained for the same cells. In these experiments, AVCN neurons were identified using intracellular labelling with neurobiotin. Successful results using a combination of whole-cell recordings, neurobiotin identification and immunolabelling were obtained for a total of 10 AVCN neurons. Analysis of the results revealed a positive, statistically significant correlation between mean receptor cluster size and mean mIPSC amplitude (P < 0.05, 10 cells, Spearman's correlation test). 4. These results provide direct experimental evidence supporting a hypothesis of central glycinergic transmission in which synaptic strength may be regulated by changes in the size of the postsynaptic receptor region.

Animals↗
PubMed1999

Male breast carcinoma: a review of 229 patients who presented to the Princess Margaret Hospital during 40 years: 1955-1996.

BACKGROUND: A single-institution review of clinical presentation, treatment, and outcome of male breast carcinoma was conducted. METHODS: Data obtained by chart review of 229 cases were analyzed with respect to clinical presentation, treatment choice, significant prognostic factors, and survival. The patients were analyzed both as a single cohort and as four cohorts grouped according to decade of diagnosis. RESULTS: Presentation occurred at a median age of 63 years, most often with a self-detected lump. Pathology consisted of subtypes similar to those of female breast carcinoma. The majority of tumors were larger than 2 cm in greatest dimension. Lymph node status, hormone receptors, and histologic and nuclear grade were underreported. Primary, adjuvant, and advanced disease treatment practices were reviewed over time. The 5-year disease free survival (DFS), overall survival (OS), and local control were 47%, 53%, and 91%, respectively. No difference in outcome by decade of diagnosis was observed. Negative lymph nodes and adjuvant hormone treatment predicted for better DFS and OS. Younger age and Stage 0 also predicted for better OS. CONCLUSIONS: Compared with data from female breast carcinoma patients, 5-year OS for this series was low; however, when these patients were separated by lymph node status, survival was similar for those with axillary lymph node metastases. Despite a change in standard primary surgical treatment and an increased use of chemotherapy and hormone therapy over the study period, no difference in outcome was observed among these males. In the absence of prospective, randomized clinical trials, collection of comprehensive data on the presentation and management of male breast carcinoma may help to optimize clinical care.

Adult↗
PubMed1999

Effects of local heparin administration on coronary thrombin activity during percutaneous transluminal coronary angioplasty.

Simultaneously obtained blood samples from the coronary sinus and systemic arterial circulation were analyzed for antithrombin III (ATIII) activity and fibrinopeptide A (FpA) concentration in nine patients undergoing elective PTCA in order to determine the effects of locally delivered heparin. Samples were obtained at the following designated times: prior to the administration of systemic heparin (period I); 5 min following a loading dose of systemic heparin (period II); 5 min following the final balloon inflation but prior to local delivery (period III); and 5 min following the administration of 4,000 units of unfractionated heparin using a local delivery catheter system (period IV). We found consistent increases in both systemic arterial (P = 0.006) and coronary sinus (P = 0.0002) ATIII activity with systemic heparinization designed to prolong the activated clotting time to 300 sec. However, local delivery of heparin further increased coronary sinus ATIII activity (P = 0.003, period III vs. period IV). FpA concentration decreased in both systemic arterial (P < 0.0001) and coronary sinus (P < 0. 0001) samples following systemic heparinization. Moreover, local delivery of heparin further decreased coronary sinus FpA concentration (P = 0.04). Thus, on a background of intense anticoagulation during PTCA, the local delivery of 4,000 units of unfractionated heparin confers incremental antithrombotic activity. Cathet. Cardiovasc. Intervent. 48:84-88, 1999.

Angioplasty, Balloon, Coronary↗
PubMed1999

Morphological and reproductive characteristics of male mosquitofish (Gambusia affinis holbrooki) inhabiting sewage-contaminated waters in New South Wales, Australia.

The potential effects of exposure of fish to reproductive endocrine disruptors (REDs) is of major concern. This study reports on the effects of sewage effluent exposure on morphology of male mosquitofish (Gambusia a. holbrooki) in a tributary of the Hawksbury-Nepean River system in New South Wales, Australia. The growth and development of the modified anal fin (the gonopodium, GP) is a secondary sexual characteristic in males, forms under the influence of testosterone, and is critical for sperm transfer. The GP was reduced in length in males sampled downstream from a sewage treatment plant discharge point compared to GP fin length in males upstream or from other comparison sites. The reduction in size of this androgen-dependent structure suggests the presence of RED substances in the water. The presence or absence of spermatozeugmata (sperm packet) was not related to a reduction in GP length, which suggests spermatogenesis may not be reduced, but other measures of fertility remain to be evaluated. These results are discussed in the context of RED contaminants associated with sewage effluent.

Analysis of Variance↗
PubMed1999

Expression of superoxide dismutases, catalase, and glutathione peroxidase in glioma cells.

Four primary antioxidant enzymes were measured in both human and rat glioma cells. Both manganese-containing superoxide dismutase (MnSOD) and copper-zinc-containing superoxide dismutase (CuZnSOD) activities varied greatly among the different glioma cell lines. MnSOD was generally higher in human glioma cells than in rat glioma cells and relatively higher than in other tumor types. High levels of MnSOD in human glioma cells were due to the high levels of expression of MnSOD mRNA and protein. Heterogeneous expression of MnSOD was present in individual glioma cell lines and may be due to subpopulations or cells at different differentiation stages. Less difference in CuZnSOD, catalase, or glutathione peroxide was found between human and rat glioma cells. The human glioma cell lines showed large differences in sensitivity to the glutathione modulating drugs 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU) and buthionine sulfoximine (BSO). A good correlation was found between sensitivity to BCNU and the activities of catalase in these cell lines. Only one cell line was sensitive to BSO and this line had low CuZnSOD activity.

Animals↗
PubMed1999

Cataract and age-related maculopathy: the Blue Mountains Eye Study.

PURPOSE: To assess the relationship between different types of cataract or past cataract surgery and late or early age-related maculopathy (ARM) in an older population. METHODS: A population-based survey examined 3,654 people aged >/=49 years, 82% of permanent residents of an area near Sydney, Australia. Participants had a detailed eye examination, including standardised dilated lens and stereo macular photographs. Presence of cataract and ARM was diagnosed from masked photographic grading using the Wisconsin Cataract and Age-related Maculopathy Grading Systems. Generalized Estimating Equation (GEE) and logistic regression models were used in the statistical analysis. RESULTS: Higher prevalence was found for both late and early ARM in eyes with cataract or a past history of cataract surgery. However, after adjusting for age, sex and other ARM risk factors, no consistent association was found between presence of cortical, nuclear or posterior subcapsular (PSC) cataract or past history of cataract surgery and either late or early ARM. In the GEE model, the only statistically significant association found was between PSC and late ARM. Non-significant increased odds were found for late ARM in eyes with cortical cataract. However, detailed analyses of cortical cataract location failed to show a relationship. CONCLUSIONS: The co-existence of cataract and ARM was almost entirely explained by the age-related increase in prevalence of both conditions. We found no evidence of a consistent relationship between cortical, nuclear or PSC cataract or history of past cataract surgery and either late or early ARM, after adjusting for age and other potential ARM risk factors. The possibility of a relationship between PSC and late ARM or between cortical cataract and any ARM was not excluded. Long-term follow up data from this population will be useful.

Age Factors↗
PubMed1999

Anterior only fusion for scoliosis in patients with myelomeningocele.

A series of patients with single major scoliosis curvatures attributable to spina bifida treated by anterior only spinal fusion was studied for 2 years to determine whether the infection rate could be decreased, adequate correction and pelvic balance could be provided, and posterior surgery could be avoided in these patients. Anterior surgery alone was performed for thoracolumbar scoliosis greater than 45 degrees if the compensatory thoracic curve was less than 40 degrees and there was no significant junctional kyphosis. Fourteen patients were treated at a mean age of 11.9 years (range, 7-16 years), with a mean curve of 64 degrees (range, 51 degrees-85 degrees), and motor levels distributed from T10-L4. Thirteen patients had prior neurosurgery for tether, syrinx, or Arnold-Chiari malformation. The spine was fused over a mean of seven vertebrae. A 3/16 inch Texas Scottish Rite Hospital rod was used most commonly (10 patients). Blood loss averaged 1100 cc. The mean curve correction was 57% at 40 months after surgery. Loss of correction occurred primarily by adding on outside the instrumented area. Mean pelvic obliquity was improved from 16 degrees to 9 degrees. There was one superficial infection. Results were good in five patients, fair in four, and poor in five. Failures were attributable to proximal decompensation in two patients who required revision surgery (two), neurologic deterioration in two, and screw pullout in one. Both patients with decompensation had syringomyelia. Both patients with neurologic deterioration had large curves (> 75 degrees). Both patients recovered after rod removal. Retrospectively, by eliminating patients with syrinx or with a curve greater than 75 degrees, all poor results would be eliminated. Anterior only fusion and instrumentation may have significant advantages, but only for selected patients with thoracolumbar curves less than 75 degrees, compensatory curves less than 40 degrees, no increased kyphosis, and no syrinx. Quadriceps function should be monitored. On the basis of this preliminary experience, continued use of this approach using stricter selection seems warranted.

Activities of Daily Living↗
PubMed1999

Refractive associations with cataract: the Blue Mountains Eye Study.

PURPOSE: To assess the relationship between myopia and age-related cataract in a defined older population. METHODS: A cross-sectional study of 3654 people aged 49 to 97 years was conducted in the Blue Mountains near Sydney, Australia, from 1992 through 1994. General medical, eye, and refractive history and information about confounders were collected by questionnaire. Participants had a detailed determination of refraction, and the spherical equivalent refraction of each eye was calculated. The Wisconsin Cataract Grading System was used in masked grading of slit lamp and retroillumination lens photographs, to assess presence and severity of nuclear, cortical, and posterior subcapsular (PSC) cataract. Data from both eyes were analyzed by the generalized estimating equation method, adjusting for cataract risk factors. RESULTS: Included in the analysis were 7308 eyes. A history of wearing distance glasses, excluding eyes with current hyperopic refraction, was used as a proxy for myopia. Subjects who had worn distance glasses were more likely to have nuclear cataract (odds ratio [OR] 1.3; confidence interval [CI] 1.0-2.1). After stratification by age at first wearing distance glasses, this relationship remained only for people who first wore distance glasses after age 40 years (OR 1.3; CI 1.0-1.8), which suggested a myopic refractive shift from developing nuclear opacity and was supported by the weak association found between current myopic refraction and nuclear cataract (OR 1.3; CI 1.0-1.6). Eyes with onset of myopia before age 20 years had the greatest PSC cataract risk (OR 3.9; CI 2.0-7.9). This was supported by the finding of an association between current myopic refraction and PSC cataract (OR 2.5; CI 1.6-4.1). PSC cataract was inversely associated with hyperopia (OR 0.6; CI 0.4-0.9). Refraction-related increasing odds were found between PSC cataract and myopia: low myopia (OR 2.1; CI 1.4-3.5), moderate myopia (OR 3.1; CI 1.6-5.7), and high myopia (OR 5.5; CI 2.8-10.9). High myopia was associated with PSC, cortical, and late nuclear cataract. CONCLUSIONS: Early-onset myopia (before age 20 years) may be a strong and independent risk factor for PSC cataract. The findings suggest the possibility of a dose response between levels of myopia and PSC cataract. Nuclear cataract was associated with presumed acquired myopia, whereas high myopia was associated with all three types of cataract.

Age Factors↗
PubMed1998

Overexpression of glia maturation factor (GMF) in PC12 pheochromocytoma cells activates p38 MAP kinase, MAPKAP kinase-2, and tyrosine hydroxylase.

In order to study the intracellular regulatory function of glia maturation factor (GMF) in neuronal cells, we achieved a 10-fold overexpression of GMF in the rat pheochromocytoma cell line PC12 by infection with a replication-defective human adenovirus carrying a rat GMF cDNA insert. These cells showed a 3.6-fold increase in the activity of p38 MAP kinase, a 3.8-fold increase in the activity of MAPKAP-K2 (MAP kinase-activated protein kinase 2), and a 4.2-fold increase in the activity of tyrosine hydroxylase (TH). We also detected an increase in the phosphorylation of TH and the 25-kDa heat shock protein (Hsp25) without a concomitant increase in their corresponding protein levels, suggesting a posttranslational modification. It was previously established that in PC12 cells, MAPKAP-K2 is an immediate target of p38, and both TH and Hsp25 are immediate targets of MAPKAP-K2. The current in vivo results are in concordance with our earlier in vitro finding that GMF promotes the activity of p38, and they implicate the participation of GMF in stress-induced catecholamine synthesis.

Animals↗
PubMed1998

Developmental changes in EPSC quantal size and quantal content at a central glutamatergic synapse in rat.

1. Developmental changes in amplitude and time course of single-fibre-evoked and spontaneous EPSCs mediated by AMPA and NMDA receptors at the endbulb-bushy cell synapse of rats from 4 to 22 days of age were recorded using whole-cell patch-clamp methods in in vitro slices of cochlear nucleus. 2. The mean conductance of the AMPA component of evoked EPSCs increased by 66 %, while that of the NMDA component decreased by 61 %, for 12- to 18-day-old rats cf. 4- to 11-day-old rats. 3. The mean AMPA spontaneous EPSC conductance increased by 54 %, while mean NMDA spontaneous EPSC conductance decreased by 83 %, for 12- to 22-day-old rats cf. 4- to 11-day-old rats. The mean number of quanta contributing to peak evoked AMPA conductance also increased by 78 % in the older age group, after correction for the asynchrony of evoked quantal release. 4. The decay time constant of spontaneous AMPA EPSCs showed a small decrease in older animals, while the decay time constant of spontaneous NMDA EPSCs was markedly decreased in older animals. The decay time constants of evoked NMDA EPSCs showed a quantitatively similar decrease to that of spontaneous NMDA EPSCs. This suggests that AMPA receptor subunit composition is unlikely to undergo developmental change, while NMDA receptor subunit composition may be substantially altered during synaptic maturation. 5. These data are consistent with a developmentally increased efficacy of AMPA receptor-mediated synaptic transmission at the endbulb-bushy cell synapse, due to an increase in underlying AMPA-mediated quantal size and content during the same period as a transient co-localization of NMDA receptors.

Animals↗
PubMed1998

Cataract associations with pinguecula and pterygium: the Blue Mountains Eye Study.

PURPOSE: To determine associations between cataract types and pinguecula and pterygium. METHODS: The Blue Mountains Eye Study examined 3,654 persons aged 49 to 97 years near Sydney, Australia. A questionnaire was used to collect information on cataract risk factors. Slit-lamp examination recorded pinguecula and pterygium. Masked lens photograph grading assessed cataract. RESULTS: Pinguecula, found in 2,418 right eyes and 2,437 left eyes, was statistically significantly associated with cortical cataract (odds ratio [OR] = 1.40) after multivariate adjustment. Pterygium, found in 199 right eyes and 188 left eyes, was associated with posterior subcapsular cataract (OR = 1.90). CONCLUSIONS: Associations were found between cataract and the presence of either pinguecula or pterygium. These findings provide indirect support for Watermen Study findings, which link ultraviolet radiation to cataract.

Aged↗
PubMed1998

Overexpression of glia maturation factor in C6 cells promotes differentiation and activates superoxide dismutase.

In order to evaluate the intracellular function of glia maturation factor (GMF), we overexpressed GMF in C6 rat glioma cells using two methods: stable transfection using the pcDNA3 plasmid, and transient transfection using replication-defective human adenovirus. With both methods, C6 cells transfected with GMF and overexpressing the protein exhibit a lower saturation density in culture compared to non-transfected or vector alone controls. Transfected cells also exhibit morphological differentiation as shown by the outgrowth of cell processes. When inoculated into nude mice, transfected cells are less tumorigenic than controls, and express the mature astrocytic marker glial fibrillary acidic protein. In tissue culture, transfected cells show a 3.5-fold increase in CuZn-dependent superoxide dismutase (CuZnSOD) activity. Western blot analysis reveals a 3.5-fold increase in CuZnSOD protein, suggesting an induction of the enzyme. In view of recent findings that reactive oxygen species (ROS) and the antioxidant enzymes are intricately involved in key physiologic processes such as proliferation, differentiation and apoptosis, the study raises the possibility that CuZnSOD may be a mediator of GMF function.

Adenoviruses, Human↗
PubMed1998

Risk factors and outcomes associated with identification of Aspergillus in respiratory specimens from persons with HIV disease. Pulmonary Complications of HIV Infection Study Group.

STUDY OBJECTIVES: To examine the significance of previously suggested risk factors and assess outcomes associated with Aspergillus identification in respiratory specimens from HIV-seropositive individuals. DESIGN: This was a nested case-control study. Patients who had Aspergillus species identified in respiratory specimens were matched at the time of study entry 1:2 with control subjects according to study center, age, gender, race, HIV transmission category, and CD4 count. SETTING: The multicenter Pulmonary Complications of HIV Infection Study. PARTICIPANTS: HIV-seropositive study participants. MEASUREMENTS AND RESULTS: Between November 1988 and March 1994, Aspergillus species were detected in respiratory specimens from 19 (1.6%) participants. The rate of Aspergillus identification among participants with CD4 counts <200 cells per cubic millimeter during years 2 through 5 after study entry ranged from 1.2 to 1.9%. Neutropenia, a CD4 count <30 cells per cubic millimeter, corticosteroid use, and Pneumocystis carinii infection were associated with subsequent identification of Aspergillus in respiratory specimens. Cigarette and marijuana use, previously suggested risk factors, were not associated with Aspergillus respiratory infection. A substantially greater proportion of patients with Aspergillus compared with control subjects died during the study (90% vs 21%). Excluding four cases first diagnosed at autopsy, 67% died within 60 days after Aspergillus was detected. CONCLUSIONS: Although Aspergillus is infrequently isolated from HIV-infected persons, the associated high mortality would support serious consideration of its clinical significance in those with advanced disease and risk factors.

AIDS-Related Opportunistic Infections↗
PubMed1997

Ischemic preconditioning in unstable coronary syndromes: evidence for time dependence.

OBJECTIVES: We hypothesized a time-dependent relation between angina occurring spontaneously before percutaneous transluminal coronary angioplasty (PTCA) and the likelihood of an ischemic response during initial balloon occlusion. We further hypothesized that the ability to elicit the "classic" mode of PTCA-related preconditioning would vary with the interval from clinical angina to PTCA. BACKGROUND: Antecedent angina represents a potential for myocardial preconditioning in unstable ischemic coronary syndromes. METHODS: We studied 67 patients with Braunwald class III unstable coronary syndromes undergoing PTCA. The interval between the last spontaneous episode of angina preceding PTCA and initial balloon inflation was categorized as follows: 0 to 6 h; 6 to 12 h; 12 to 24 h; and >24 h. RESULTS: Across the various intervals, there was a significant difference (p = 0.004) in the proportion of patients with an absent ischemic response during the first balloon inflation (0 to 6 h, 50%; 6 to 12 h, 35%; 12 to 24 h, 23%; and >24 h, 4%). There was, however, no difference between the first and second inflations in the proportion of patients with a diminished ischemic response until 6 to 12 h (p = 0.017) had elapsed since the last spontaneous episode of angina. Patients whose angina last occurred >24 h before the first inflation showed the greatest inducibility of PTCA-related preconditioning. CONCLUSIONS: Strong evidence exists for the occurrence of ischemic preconditioning in unstable coronary syndromes. Although the protective effect of spontaneous angina appears to wane beyond 6 h, recovery of preconditioning occurs from 6 to 12 h. Thus, preconditioning can be reinduced during PTCA with a marked potentiation of the effect at 24 h. This suggests an underlying time-dependent mechanism with a physiologic "half-life" of 6 to 12 h.

Angina, Unstable↗
PubMed1997

Femoral complications and bed rest duration after coronary arteriography.

This randomized study using a pneumatic compression device found no significant difference in the femoral complication rate between 4 and 6 hours of bed rest after Judkin's coronary arteriography. The positive implications for the organization of an efficient service in busy tertiary centers include reduced patient discomfort, earlier ambulation and discharge, efficient staff deployment, and enhanced throughput.

Adult↗