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Biomedical subjects

Y M Lam

Publications and source records attributed to Y M Lam.

At least 19 recordsLinked to original sources
PubMed2006

Controlled synthesis and association behavior of graft Pluronic in aqueous solutions.

Poly(vinyl pyrrolidone) (PVP) was grafted onto Pluronic F127 (PEO-PPO-PEO) to produce novel amphiphilic PVP-g-F127 graft copolymers. A controlled synthesis method was used to graft PVP onto different parts of F127. Two types of graft polymers were obtained: one has PVP grafted onto the PEO part of F127 and the other has PVP grafted onto the PPO part of F127. The association behavior of the two modified polymers was examined using differential scanning calorimetry, surface tension measurements, and dynamic light scattering.

Journal Article↗
PubMed2006

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↗
PubMed2005

Poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide)-g-poly(vinylpyrrolidone): association behavior in aqueous solution and interaction with anionic surfactants.

In this work, we aimed to study the association and interaction behavior of poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide) block copolymers grafted with poly(vinylpyrrolidone). Critical micellization concentrations were determined using fluorescent probes (pyrene) and critical micellization temperatures characterizing temperature-dependent transitions from monomers to multimolecular micelles were measured. The thermal responsiveness of the copolymer is not affected by the grafting. The hydrodynamic radius of the graft copolymer micelles is found to be greater than that of the original copolymer micelles. The graft copolymer is found to form anisotropic aggregates. The structure of the graft copolymer micelles is less disrupted by the anionic surfactant sodium dodecyl sulfate, compared to the ungraft copolymer.

Journal Article↗
PubMed2003

Multiple brain abscesses in a patient with bilateral pulmonary arteriovenous malformations and immunoglobulin deficiency.

A 34 year old Chinese man presented with grand mal seizures complicating multiple brain abscesses caused by mixed oral flora. Because of persistent hypoxaemia contrast spiral thoracic computed tomography was done, which revealed bilateral pulmonary arteriovenous malformations (PAVMs). Concomitant IgA and IgG subclass deficiency was also found. The combination of these two conditions appears to have predisposed this patient to presumably paradoxical septic embolism. The patient's cerebral condition responded to postoperative antibiotic treatment and he eventually received selective coil embolisation of right lower lobe PAVMs, which relieved his hypoxaemia and dyspnoea.

Adult↗
PubMed2001

Bilateral massive adrenal hemorrhage. Assessment of putative risk factors by the case-control method.

Case reports and case series have identified putative risk factors for the development of bilateral massive adrenal hemorrhage (BMAH) in humans. The anatomy and physiology of the adrenal gland allow development of a model to fit the pathophysiology behind these risk factors. Until now, these risk factors were not systematically tested using analytical epidemiologic studies. A case-control study was undertaken using sources of cases and controls from multiple teaching hospitals in Ontario, Canada. The results of multivariate logistic regression indicated that thrombocytopenia (odds ratio [OR] = 14.6, 95% confidence intervals [CI] = 3.0-70.1, p < 0.001), heparin exposure of any route or type beyond 3 days (4-6 days: OR = 17.0, CI = 1.9-154.6; > 6 days: OR = 33.5, CI = 4.3-262.6; p < 0.001), and sepsis (OR = 6.3, CI = 1.2-32.2, p = 0.019) were most strongly and independently associated with development of BMAH. Another weaker positive association included invasive radiologic procedure (OR = 4.4, CI = 0.9-22.1, p = 0.055). Neither major surgery or duration of hospitalization were independent risk factors. Although coronary artery disease and possibly diabetes and hypertension appeared to be markers for lower risk of BMAH, this may be a result of bias introduced by using hospital controls ("Berkson bias"), as the effect was not explained by a protective effect of vasoactive medications. Thus, a picture of the high-risk patient should include a patient who has been treated with heparin (any route or type) beyond 3 days and has had thrombocytopenia (not necessarily induced by heparin) during the course of an illness. If the setting includes unexplained abdominal, chest, or back pain; fever; confusion; hypotension or shock; abrupt anemia; or electrolyte disorders, clinicians should not hesitate to cover empirically with lifesaving glucocorticoids while awaiting results of confirmatory tests.

Adrenal Cortex Diseases↗
PubMed2001

Continuous calcium chloride infusion for massive nifedipine overdose.

A 37-year-old woman presented with persistent hypotension and noncardiogenic pulmonary edema after massive nifedipine overdose. Judicious use of continuous and prolonged high-dose IV calcium infusion was administered to provide sustained increases in serum ionic calcium level (approximately 2 mmol/L) and was able to improve the hemodynamic status without any major adverse reaction.

Adult↗
PubMed2000

A single nucleotide polymorphism at nucleotide -1793 in the von Willebrand factor (VWF) regulatory region is associated with plasma VWF:Ag levels.

von Willebrand Factor (VWF) is a large multimeric glycoprotein involved in the transport and protection of factor VIII and in mediating platelet-subendothelium and platelet-platelet interactions. We have documented the presence of a single nucleotide polymorphism (SNP) at nucleotide (nt) -1793 (G 0.36 or C 0.64) in the VWF 5'-flanking sequence. This polymorphism is in strong linkage disequilibrium with the previously reported SNPs at nts -1234, -1185 and -1051 and, like this other group of polymorphisms, shows a significant association with plasma VWF levels. This association is more marked in subjects who are more than 40 years of age. Further, circumstantial evidence to support a role for the -1793 sequence in regulating VWF expression comes from our demonstration of differential binding of endothelial cell nuclear proteins, including the transcription factor NFkappaB, by this sequence. In summary, the association of the -1793 SNP with plasma VWF levels provides additional evidence for the role of the VWF regulatory region between nts -1793 and -1051 in controlling VWF expression.

Adult↗
PubMed2000

Reversal of left ventricular remodeling by synchronous biventricular pacing in heart failure.

Synchronous biventricular pacing is a new nonpharmacological supplemental treatment of advanced heart failure associated with electromechanical conduction delay. However, the role of pacing on left ventricular remodeling is unknown. Eleven patients with New York Heart Association Class III to IV heart failure, a left ventricular ejection fraction < 35%, and a QRS duration > or = 140 ms received a biventricular dual chamber pacemaker. Serial echocardiography, 6-minute hall walk, and Minnesota Living with Heart Failure quality-of-life (QOL) questionnaire were performed before and after up to 3 months of pacing. At 3 months there was a significant increase in fractional shortening (P < 0.001), ejection fraction (P < 0.001), and cardiac output (P < 0.05). The left ventricular end-diastolic volume (245 +/- 70 vs 185 +/- 37 mL, P < 0.05), end-systolic volume (209 +/- 69 vs 140 +/- 44 mL P < 0.05), and mitral regurgitation were reduced (P < 0.05), and diastolic filling time was lengthened (P < 0.05). There were also improvements in heart failure symptoms, an increase in 6-minute walk distance, and a decrease in QOL scores. Synchronous biventricular pacing for 3 months was associated with hemodynamic improvements, reversal of left ventricular remodeling, and increase in left ventricular systolic function, and a decrease in secondary mitral regurgitation.

Cardiac Pacing, Artificial↗
PubMed1999

Variation at the von Willebrand factor (vWF) gene locus is associated with plasma vWF:Ag levels: identification of three novel single nucleotide polymorphisms in the vWF gene promoter.

Both genetic and environmental factors contribute to the normal population variability of plasma von Willebrand Factor (vWF) levels, however, regulatory mechanisms at the vWF gene locus itself have not yet been identified. We have investigated the association between polymorphic variation in the 5'-regulatory region of the vWF gene and levels of plasma vWF:Ag in a study of 261 group O blood donors. Three novel single nucleotide polymorphisms (SNPs) were identified in the vWF promoter: C/T at -1234, A/G at -1185, and G/A at -1051. These SNPs had identical allele frequencies of 0.36 for the -1234C, -1185A, and -1051G alleles and 0.64 for the -1234T, -1185G, and -1051A alleles and were in strong linkage disequilibrium. In fact, these polymorphisms segregated as two distinct haplotypes: -1234C/-1185A/-1051G (haplotype 1) and -1234T/-1185G/-1051A (haplotype 2) with 12.6% of subjects homozygous for haplotype 1, 40. 6% homozygous for haplotype 2, and 42.5% of subjects heterozygous for both haplotypes. Only 4.3% of individuals had other genotypes. A significant association between promoter genotype and level of plasma vWF:Ag was established (analysis of covariance [ANCOVA], P =. 008; Kruskal-Wallis test, P =.006); individuals with the CC/AA/GG genotype had the highest mean vWF:Ag levels (0.962 U/mL), intermediate values of vWF:Ag (0.867 U/mL) were observed for heterozygotes (CT/AG/GA), and those with the TT/GG/AA genotype had the lowest mean plasma vWF:Ag levels (0.776 U/mL). Interestingly, when the sample was subgrouped according to age, the significant association between promoter genotype and plasma vWF:Ag level was accentuated in subjects > 40 years of age (analysis of variance [ANOVA], P =.003; Kruskal-Wallis test, P =.001), but was not maintained for subjects </= 40 years of age (ANOVA, P >.4; Kruskal-Wallis test, P >.4). In the former subgroup, mean levels of plasma vWF:Ag for subjects with the CC/AA/GG, CT/AG/GA, and TT/GG/AA genotypes were 1.075, 0.954, and 0.794 U/mL, respectively. By searching a transcription factor binding site profile database, these polymorphic sequences were predicted to interact with several transcription factors expressed in endothelial cells, including Sp1, GATA-2, c-Ets, and NFkappaB. Furthermore, the binding sites at the -1234 and -1051 SNPs appeared to indicate allelic preferences for some of these proteins. Electrophoretic mobility shift assays (EMSAs) performed with recombinant human NFkappaB p50 showed preferential binding of the -1234T allele (confirmed by supershift EMSAs), and EMSAs using bovine aortic endothelial cell (BAEC) nuclear extracts produced specific binding of a nuclear protein to the -1051A allele, but not the -1051G allele. These findings suggest that circulating levels of vWF:Ag may be determined, at least in part, by polymorphic variation in the promoter region of the vWF gene, and that this association may be mediated by differential binding of nuclear proteins involved in the regulation of vWF gene expression.

Adult↗
PubMed1997

Technical note: CT determination of the mineral density of dry bone specimens using the dipotassium phosphate phantom.

Recent studies have demonstrated the potential application of computed tomography (CT) in research into bone density. Clinical studies of bone density using CT commonly employ a dipotassium phosphate phantom to calibrate measurements of mineral density. Designed for in vivo studies, the use of this phantom requires that bones be scanned while immersed in and permeated by fluids or soft tissues similar to water in X-ray attenuation coefficient. However, this condition may not always be met in anthropological applications, which often involve rare and fragile specimens. This study compares mineral density values calculated for a sample of bones scanned-at the same sites-in air and in water. The results indicate that, when scanned in air, the mineral density of trabecular bone is dramatically underestimated, while that of cortical bone is slightly overestimated. We present a linear regression equation to correct this error but recommend that, when possible, researchers calculate their own regressions based on their specific scanning conditions.

Animals↗
PubMed1997

Extent and variation of omeprazole prescribing in an elderly population of Ontario.

OBJECTIVE: To determine the extent of omeprazole prescribing in the senior population of Ontario over a 1-year period; the variation in omeprazole prescribing for this population according to age group, gender, and geographic region: and the extent of inappropriate prescribing of omeprazole for this population. DESIGN: Retrospective drug utilization review of prescription drug insurance claims. DATA SOURCE: The Ontario Drug Benefit (ODB) program claims database. OUTCOME MEASURES: The following outcomes were measured: the proportion of seniors in Ontario who received a prescription for omeprazole from April 1, 1992 to March 31, 1993: effects of age group, gender, and geographic region of residence on omeprazole prescribing; and the extent of inappropriate omeprazole prescribing according to the ODB criteria for use. Prescribing of omeprazole was defined as inappropriate if a first-line antiulcer drug (i.e., histamine2-receptor antagonist) was not prescribed within 1-6 months of the first prescription claim for omeprazole. RESULTS: A total of 29,936 seniors in Ontario received omeprazole from April 1, 1992 to March 31, 1993 (2.53 recipients per 100 eligible population). The age-gender group most frequently prescribed omeprazole was women 65-74 years, followed by women and men 75 years or older, and then men 65-74 years. Omeprazole prescribing varied widely among the 48 provincial counties (range of 1.66 recipients per 100 eligible population to 4.52 recipients per 100 population, p < 0.001). There was no evidence of a clustering effect in omeprazole prescribing at the county level. Prescribing of omeprazole was considered to be inappropriate for 80.5% of recipients. CONCLUSIONS: This study demonstrated the ineffectiveness of the ODB limited-use program in controlling omeprazole prescribing. Further study should be done to examine determinants of variation in prescribing by geographic region.

Age Factors↗
PubMed1997

Expression of the MRP and MDR1 multidrug resistance genes in small cell lung cancer.

Acquired multidrug resistance is a major obstacle to a cure for small cell lung cancer (SCLC). Overexpression of the MDR1 gene occurs infrequently in multidrug-resistant SCLC cell lines. The multidrug resistance protein (MRP) can confer multidrug resistance, but its role in clinically acquired drug resistance is unknown. The purpose of this study was to measure expression of MRP and MDR1 mRNA in cell lines and clinical samples from SCLC patients and to correlate the results with drug sensitivity profiles. Twenty-three SCLC cell lines and 10 tumor samples from SCLC patients were examined. Samples expressing MRP and MDR1 were identified by reverse transcription-PCR, and levels of MRP mRNA in the cell lines were measured by quantitative reverse transcription-PCR. One of 23 cell lines (4%) expressed MDR1 mRNA, whereas MRP expression was detected in 19 of 23 cell lines (83%). There was a significant correlation between doxorubicin resistance and MRP expression levels (r = 0.422; P = 0.045). Of the 10 clinical samples, 3 expressed only MRP, 2 expressed only MDR1, and 4 expressed both drug resistance genes. In summary, MRP is frequently expressed in clinical samples and cell lines from SCLC patients, and the levels correlate with doxorubicin resistance in unselected SCLC cell lines. Expression of MDR1 can be detected in clinical samples of SCLC but is rarely found in cell lines from drug-resistant patients. These multidrug resistance proteins may contribute to the multifactorial problem of clinically acquired drug resistance in SCLC.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1996

Mechanisms of resistance of human small cell lung cancer lines selected in VP-16 and cisplatin.

BACKGROUND: The combination of VP-16 and cisplatin is one of the most active regimens available for the treatment of small cell lung cancer (SCLC), however, most tumors eventually become resistant to these drugs. METHODS: To investigate the problem of resistance to VP-16 and cisplatin in patients with SCLC, we established two resistant sublines from the drug sensitive human SCLC line, NCI-H209, by in vitro selection in VP-16 and cisplatin. RESULTS: The VP-16-selected cell line, H209/VP, was more than 100-fold resistant to VP-16, and displayed cross-resistance to VM-26 and other topoisomerase II interactive drugs, but not to vinca alkaloids. There was no difference in accumulation of VP-16 in H209/VP compared with its parent cell line. The level of topoisomerase II-alpha was reduced to 8% of that in the parent cell line, and there was an altered form of this enzyme with a molecular weight of 160 kilodaltons (kDa), in addition to the normal 170 kDa protein. The cisplatin-selected cell line, H209/CP, was 11.5-fold resistant to cisplatin, with only a low level of cross-resistance to other platinum compounds including carboplatin, tetraplatin, iproplatin, and lobaplatin. This line was highly cross-resistant to vinca alkaloids, but not to anthracyclines or epipodophyllotoxins. The H209/CP cell line was not resistant to cadium chloride, suggesting that alterations in metallothionein are unlikely to be a cause of resistance. Although glutathione (GSH) levels were increased nearly 2-fold in H209/CP, there was no difference in levels of the GSH-related enzymes glutathione-S-transferase, glutathione peroxidase, and glutathione reductase, compared with the parent line. The H209/CP line had a 1.4-fold elevation of topoisomerase II-alpha. The accumulation of cisplatin was reduced in this cell line, and there were fewer DNA-interstrand cross links formed in the presence of cisplatin in H209/CP, compared with the parent line. Neither H209/VP nor H209/CP expressed MDR1, the gene for P-glycoprotein. The MRP gene was expressed at a slightly higher level in the H209/VP cell line, but there was no significant increase in expression of this gene in the H209/CP cell line. CONCLUSIONS: The resistance of the H209/VP cell line is associated with an alteration of topoisomerase II-alpha, whereas the resistance in the H209/CP line is associated with reduced drug accumulation.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1996

Chin morphology and sexual dimorphism in the fossil hominid mandible sample from Klasies River Mouth.

The site of Klasies River Mouth (KRM) in South Africa has produced a small sample of early Upper Pleistocene hominid remains that have been a focus for discussions of the origins of modern humans. Despite certain primitive characteristics exhibited by these fossils, proponents of a single recent origin have attributed them to early modern humans. Critics of this hypothesis have emphasized the significance of the archaic features evident in this sample, including the absence of pronounced chins among the mandibular specimens. This study compares the size range and chin morphology exhibited by the KRM mandibles with that of Neandertals, Upper Pleistocene humans, and recent humans. The extreme sexual dimorphism documented among the KRM fossils reflects the presence of a very small individual, and previous efforts to classify the KRM sample as archaic on the basis of their robusticity have failed to address the significance of this diminutive hominid. While each KRM fossil falls within the 95% envelope of variability established for chin development in a comparative modern sample, a similarly low frequency of pronounced chins is very unlikely to be found in any recent human population. The morphological pattern of the KRM mandibles is clearly distinct from that of Neandertals and of recent humans.

Animals↗
PubMed1993

Do glutathione and related enzymes play a role in drug resistance in small cell lung cancer cell lines?

Small cell lung cancer (SCLC) is treated primarily with combination chemotherapy. Despite high initial response rates, most patients eventually die with drug resistant disease. In some tumours, resistance to multiple chemotherapeutic agents is attributed to overexpression of P-glycoprotein (P-gp). However, this does not appear to be a frequent occurrence in drug resistant SCLC. Increased levels of glutathione (GSH) and related enzymes may play a role in resistance to alkylating agents as well as natural product drugs. We measured levels of GSH, glutathione S-transferase (GST), glutathione reductase (GSH Red), glutathione peroxidase (GSH Px), and gamma-glutamyl transpeptidase (gamma-GT) in a panel of 20 SCLC cell lines. Most of these lines were established from patients treated at this centre. Each cell line had a characteristic and reproducible profile of GSH and related enzyme levels. Immunoblot analysis indicated that the predominant GST in the cell lines was the anionic pi isoenzyme. The relative sensitivity of each of these cell lines to 16 different chemotherapeutic agents was measured using a modified MTT assay. Spearman rank correlation analysis was used to determine the relationships between the relative chemosensitivity of these cell lines and the levels of GSH and related enzymes. The number of positive correlations was no greater than expected by chance alone. Furthermore, there was no correlation with the treatment history of the patients from whom the cell lines were derived. These data suggest that alterations in glutathione metabolism do not play a major role in resistance to chemotherapeutic agents in these human SCLC cell lines.

Antineoplastic Agents↗
PubMed1991

Chemosensitivity testing of small cell lung cancer using the MTT assay.

A simple colorimetric test, the MTT assay, has been adapted for chemosensitivity testing of human small cell lung cancer cell lines, and fresh tumour samples. Optimal conditions for clinical chemosensitivity testing were determined using established SCLC lines. Nineteen different chemotherapeutic agents were tested, and sixteen of them were found to be cytotoxic in this assay system. The drug sensitivity of a panel of 16 SCLC cell lines was measured and compared. There was very little intraexperiment variation, but the interexperiment variation was significant. Cell lines which were derived from patients who had not received chemotherapy at the time the cell line was established were more sensitive (to all but one of the drugs) than lines derived from treated patients, and the differences were statistically significant for two of the drugs. One cell line, NCI-H209, which was derived from an untreated patient, stood out as being the most sensitive or among the most sensitive to all of the drugs tested. Another cell line, H69AR, which is a multidrug resistant subline of the cell line NCI-H69, was the most resistant to many of the natural product drugs tested. Multiple drug chemosensitivity testing was performed on eight fresh tumour samples from SCLC patients (five pleural effusions, one lymph node, and two primary tumours). It was possible to perform chemosensitivity testing on all of the clinical samples in which sufficient tumour cells were available. The drug sensitivity of the clinical samples was, in most cases, within the same range as for the cell lines. Since this assay is very rapid and simple to perform, it may have practical applications in clinical drug sensitivity testing of human tumours.

Antineoplastic Agents↗
PubMed1991

Relationship between newborn and maternal iron status and haematological indices.

The haemoglobin, mean corpuscular volume, mean corpuscular haemoglobin, haematocrit, serum iron and total iron binding capacity, and serum ferritin concentrations in umbilical cord blood samples taken from 96 appropriate-for-gestational age infants delivered at term were measured and compared to the respective maternal values measured at 36 weeks' gestation. All the values were higher in cord blood. Only maternal mean corpuscular volume and mean corpuscular haemoglobin were correlated with cord serum iron. Cord blood haematological indices were not correlated with either gestation at delivery or birth weight. However, newborn serum ferritin was positively correlated with gestation at delivery, while the maternal:newborn ferritin ratio was inversely correlated with gestation and birth weight. The results suggest that maternal haematological and iron indices are not predictive of the haemoglobin or iron status of the newborn, and that the fetus continues to take up iron from the mother until delivery.

Adult↗