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1.
BMJ Mil Health ; 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38688679

ABSTRACT

INTRODUCTION: ECG changes are associated with regular long-term intensive exercise due to electrical manifestations of increased vagal tone, increased ventricular wall thickness and enlarged chamber size. The aim of this study was to further understand the relationship of athletic ECG changes and athletic performance in an athletic population. METHODS: A retrospective cohort study was performed in 195 Nepali civilian males undergoing selection to the Gurkhas. V̇O2max (maximal oxygen consumption) was estimated from a 1.5-mile run time using Cooper's formula and correlated with athletic ECG adaptations. Variables were explored with univariable and multivariable linear regression. RESULTS: The median number of athletic changes on ECG was 2 (IQR 1-2). There was no significant correlation (p=0.46) between the number of ECG adaptations and the degree of cardiovascular fitness by estimated V̇O2max (estV̇O2max). We found a negligible but significant correlation between the presence of inferior T wave inversion (TWI) and estV̇O2max (R2=0.03, p=0.02). The multivariable-fitted regression model was: estV̇O2max~Intercept+presence of RVH (right ventricular hypertrophy) voltage criteria+absence of sinus arrhythmia+T wave axis+inferior TWI. The overall regression was statistically significant: R2=0.10, F(df=4, df=189)=[5.4], p=0.0004). All variables in the multivariable model significantly predicted estV̇O2max (p<0.04). CONCLUSION: ECG changes of athleticism negligibly predict and differentiate athletic performance in our athletic population. The most predictive ECG markers being voltage criteria for left ventricular hypertrophy and RVH. Markers of increased vagal tone were not predictive. TWI, being a marker for disease, was also a marker for athletic performance in this cohort. The number of athletic ECG adaptations did not predict increased athletic performance.

3.
Arch Osteoporos ; 15(1): 147, 2020 09 21.
Article in English | MEDLINE | ID: mdl-32955674

ABSTRACT

Fracture determinants differ between Canadians of Chinese and White descent, the former constituting the second largest visible minority group in Canada. The results of this study support the importance of characterizing bone health predictors in Canadians of different ethnicity to improve population-specific fracture prevention and treatment strategies. PURPOSE: We aimed to compare clinical risk factors, bone mineral density, prevalence of osteoporosis, and fractures between Chinese and White Canadians to identify ethnicity-specific risks. METHODS: We studied 236 Chinese and 8945 White Canadians aged 25+ years from the Canadian Multicentre Osteoporosis Study (CaMos). The prevalence of osteoporosis using ethnicity-specific peak bone mass (PBM), and of prior and incident low trauma fractures were assessed and compared between groups. Linear regressions, adjusting for age and anthropometric measures, were used to examine the association between baseline and 5-year changes in BMD and ethnicity. RESULTS: Chinese participants had shorter stature, lower BMI, and lower rate of falls than White participants. Adjusted models showed no significant differences in baseline BMD between ethnic groups except in younger men where total hip BMD was 0.059 g/cm2 (0.009; 0.108) lower in Chinese. Adjusted 5-year BMD change at lumbar spine was higher in older Chinese women and men compared with Whites. When using Chinese-specific PBM, the prevalence of osteoporosis in Chinese women was 2-fold lower than when using that of White women The prevalence of fractures was higher in White women compared with Chinese with differences up to 14.5% (95% CI 9.2; 19.7) and 10.5% (95% CI 4.5-16.4) in older White men. Incident fractures were rare in young Chinese compared with White participants and not different in the older groups. CONCLUSION: Our results support the importance of characterizing bone strength predictors in Chinese Canadians and the development of ethnicity-specific fracture prediction and prevention strategies.


Subject(s)
Asian People/statistics & numerical data , Bone Density , Fractures, Bone/epidemiology , Osteoporosis/epidemiology , White People/statistics & numerical data , Adult , Aged , Canada/epidemiology , Female , Fractures, Bone/ethnology , Humans , Male , Osteoporosis/ethnology , Prevalence , Risk Factors
4.
J Clin Densitom ; 20(2): 226-232, 2017.
Article in English | MEDLINE | ID: mdl-27956336

ABSTRACT

High-resolution peripheral quantitative computed tomography (HR-pQCT) quantifies bone microstructure and density at the distal tibia where there is also a sizable amount of myotendinous (muscle and tendon) tissue (MT); however, there is no method for the quantification of MT. This study aimed (1) to assess the feasibility of using HR-pQCT distal tibia scans to estimate MT properties using a custom algorithm, and (2) to determine the relationship between MT properties at the distal tibia and mid-leg muscle density (MD) obtained from pQCT. Postmenopausal women from the Hamilton cohort of the Canadian Multicenter Osteoporosis Study had a single-slice (2.3 ± 0.5 mm) 66% site pQCT scan measuring muscle cross-sectional area (MCSA) and MD. A standard HR-pQCT scan was acquired at the distal tibia. HR-pQCT-derived MT cross-sectional area (MTCSA) and MT density (MTD) were calculated using a custom algorithm in which thresholds (34.22-194.32 mg HA/cm3) identified muscle seed volumes and were iteratively expanded. Pearson and Bland-Altman plots were used to assess correlations and systematic differences between pQCT- and HR-pQCT-derived muscle properties. Among 45 women (mean age: 74.6 ± 8.5 years, body mass index: 25.9 ± 4.3 kg/m2), MTD was moderately correlated with mid-leg MD across the 2 modalities (r = 0.69-0.70, p < 0.01). Bland-Altman analyses revealed no evidence of directional bias for MTD-MD. HR-pQCT and pQCT measures of MTCSA and MCSA were moderately correlated (r = 0.44, p < 0.01). Bland-Altman plots for MTCSA revealed that larger MCSAs related to larger discrepancy between the distal and the mid-leg locations. This is the first study to assess the ability of HR-pQCT to measure MT size, density, and morphometry. HR-pQCT-derived MTD was moderately correlated with mid-leg MD from pQCT. This relationship suggests that distal MT may share common properties with muscle throughout the length of the leg. Future studies will assess the value of HR-pQCT-derived MT properties in the context of falls, mobility, and balance.


Subject(s)
Algorithms , Muscle, Skeletal/anatomy & histology , Muscle, Skeletal/diagnostic imaging , Tendons/anatomy & histology , Tendons/diagnostic imaging , Tomography, X-Ray Computed/methods , Aged , Aged, 80 and over , Ankle , Female , Humans , Leg , Middle Aged , Organ Size , Tibia/diagnostic imaging
5.
J Musculoskelet Neuronal Interact ; 16(4): 265-282, 2016 12 14.
Article in English | MEDLINE | ID: mdl-27973379

ABSTRACT

The choice of an appropriate imaging technique to quantify bone, muscle, or muscle adiposity needs to be guided by a thorough understanding of its competitive advantages over other modalities balanced by its limitations. This review details the technical machinery and methods behind peripheral quantitative computed tomography (pQCT), high-resolution (HR)-pQCT, and magnetic resonance imaging (MRI) that drive successful depiction of bone and muscle morphometry, densitometry, and structure. It discusses a number of image acquisition settings, the challenges associated with using one versus another, and compares the risk-benefits across the different modalities. Issues related to all modalities including partial volume artifact, beam hardening, calibration, and motion assessment are also detailed. The review further provides data and images to illustrate differences between methods to better guide the reader in selecting an imaging method strategically. Overall, investigators should be cautious of the impact of imaging parameters on image signal or contrast-to-noise-ratios, and the need to report these settings in future publications. The effect of motion should be assessed on images and a decision made to exclude prior to segmentation. A more standardized approach to imaging bone and muscle on pQCT and MRI could enhance comparability across studies and could improve the quality of meta-analyses.


Subject(s)
Bone and Bones/diagnostic imaging , Diagnostic Imaging/methods , Muscles/diagnostic imaging , Humans , Image Interpretation, Computer-Assisted/methods
6.
J Musculoskelet Neuronal Interact ; 14(4): 401-10, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25524965

ABSTRACT

PURPOSE: To determine the degree to which muscle density and fractures are explained by inter and intramuscular fat (IMF). METHODS: Women ⋝50 years of age (Hamilton, ON, Canada) had peripheral magnetic resonance imaging and peripheral quantitative computed tomography scans at 66% of the tibial length. Muscle on computed tomography images was segmented from subcutaneous fat and bone using fixed thresholds, computing muscle density. IMF was segmented from muscle within magnetic resonance images using a region-growing algorithm, computing IMF volume. Fracture history over the last 14 years was obtained. Odds ratios for fractures were determined for muscle density, adjusting for IMF volume, total hip BMD, age and body mass index. RESULTS: Women with a history of fractures were older (N=32, age:75.6±8.3 years) than those without (N=39, age: 67.0±5.2 years) (<0.01). IMF volume explained 49.3% of variance in muscle density (p<0.001). Odds for fractures were associated with lower muscle density even after adjusting for IMF volume but were attenuated after adjusting for age. CONCLUSIONS: Muscle adiposity represents only 50% of the muscle density measurement. Properties of muscle beyond its adiposity may be related to fractures, but larger and prospective studies are needed to confirm these associations.


Subject(s)
Adiposity , Fractures, Bone , Image Interpretation, Computer-Assisted/methods , Magnetic Resonance Imaging/methods , Tomography, X-Ray Computed/methods , Aged , Algorithms , Area Under Curve , Female , Humans , Middle Aged , Muscles/anatomy & histology , Odds Ratio , ROC Curve
7.
J Musculoskelet Neuronal Interact ; 14(3): 246-54, 2014 Sep.
Article in English | MEDLINE | ID: mdl-25198219

ABSTRACT

OBJECTIVE: To assess bone-muscle (B-M) indices as risk factors for incident fractures in men. METHODS: Participants of the Osteoporotic Fractures in Men (MrOS) Study completed a peripheral quantitative computed tomography scan at 66% of their tibial length. Bone macrostructure, estimates of bone strength, and muscle area were computed. Areal bone mineral density (aBMD) and body composition were assessed with dual-energy X-ray absorptiometry. Four year incident non-spine and clinical vertebral fractures were ascertained. B-M indices were expressed as bone-to-muscle ratios for: strength, mass and area. Discriminative power and hazards ratios (HR) for fractures were reported. RESULTS: In 1163 men (age: 77.2±5.2 years, body mass index (BMI): 28.0±4.0 kg/m(2), 4.1±0.9 follow-up years, 7.7% of men ⋝1 fracture), B-M indices were smaller in fractured men except for bending and areal indices. Smaller B-M indices were associated with increased fracture risk (HR: 1.30 to 1.74) independent of age and BMI. Strength and mass indices remained significant after accounting for lumbar spine but not total hip aBMD. However, aBMD correlated significantly with B-M indices. CONCLUSION: Mass and bending B-M indices are risk factors for fractures in men, but may not improve fracture risk prediction beyond that provided by total hip aBMD.


Subject(s)
Bone and Bones/pathology , Muscle, Skeletal/pathology , Osteoporotic Fractures/pathology , Absorptiometry, Photon , Aged , Aged, 80 and over , Body Composition , Bone Density , Hand Strength , Humans , Male , Osteoporotic Fractures/epidemiology , Risk Factors
8.
Child Care Health Dev ; 39(2): 213-9, 2013 Mar.
Article in English | MEDLINE | ID: mdl-22066653

ABSTRACT

BACKGROUND: Shyness in late childhood is related to social and psychological problems. The present study examined the relations among shyness, attributional styles and self-esteem. It was hypothesized that self-esteem mediated the effects of attributional styles on shyness. METHODS: Self-reported data on degree of shyness, attributional styles and self-esteem were obtained from 326 Chinese children with mean age of 10.85 years. RESULTS: It was found that positive attributional styles predicted shyness in the negative direction and the effects were fully mediated by self-esteem, and negative attributional styles predicted shyness in the positive direction both directly and through self-esteem. CONCLUSION: The results imply that how children attribute positive and negative outcomes affect both self-esteem and shyness. It is suggested that practitioners should conduct attribution-retraining workshops for shy children and help teachers and parents learn how to mitigate negative attributional style and foster positive attributional styles in children.


Subject(s)
Internal-External Control , Self Concept , Shyness , Child , Child Behavior , Female , Humans , Male , Models, Psychological , Psychometrics
9.
Anim Genet ; 44(3): 305-10, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23134432

ABSTRACT

Although variation in the KIT gene is a common cause of white spotting among domesticated animals, KIT has not been implicated in the diverse white spotting observed in the dog. Here, we show that a loss-of-function mutation in KIT recapitulates the coat color phenotypes observed in other species. A spontaneous white spotting observed in a pedigree of German Shepherd dogs was mapped by linkage analysis to a single locus on CFA13 containing KIT (pairwise LOD = 15). DNA sequence analysis identified a novel 1-bp insertion in the second exon that co-segregated with the phenotype. The expected frameshift and resulting premature stop codons predicted a severely truncated c-Kit receptor with presumably abolished activity. No dogs homozygous for the mutation were recovered from multiple intercrosses (P = 0.01), suggesting the mutation is recessively embryonic lethal. These observations are consistent with the effects of null alleles of KIT in other species.


Subject(s)
Dogs/genetics , Frameshift Mutation , Hair Color/genetics , Proto-Oncogene Proteins c-kit/genetics , Animals , Chromosome Mapping , Computational Biology , Female , Genetic Linkage , Genetic Pleiotropy , Genetic Variation , Genotype , Homozygote , Pedigree , Sequence Analysis, DNA
10.
Tissue Antigens ; 76(2): 110-8, 2010 Aug.
Article in English | MEDLINE | ID: mdl-20403140

ABSTRACT

Necrotizing meningoencephalitis (NME) is a disorder of Pug Dogs that appears to have an immune etiology and high heritability based on population studies. The present study was undertaken to identify a genetic basis for the disease. A genome-wide association scan with single tandem repeat (STR) markers showed a single strong association near the dog leukocyte antigen (DLA) complex on CFA12. Fine resolution mapping with 27 STR markers on CFA12 further narrowed association to the region containing DLA-DRB1, -DQA1 and, -DQB1 genes. Sequencing confirmed that affected dogs were more likely to be homozygous for specific alleles at each locus and that these alleles were linked, forming a single high risk haplotype. The strong DLA class II association of NME in Pug Dogs resembles that of human multiple sclerosis (MS). Like MS, NME appears to have an autoimmune basis, involves genetic and nongenetic factors, has a relatively low incidence, is more frequent in females than males, and is associated with a vascularly orientated nonsuppurative inflammation. However, NME of Pug Dogs is more aggressive in disease course than classical human MS, appears to be relatively earlier in onset, and involves necrosis rather than demyelination as the central pathobiologic feature. Thus, Pug Dog encephalitis (PDE) shares clinical features with the less common acute variant forms of MS. Accordingly, NME of Pug Dogs may represent a naturally occurring canine model of certain idiopathic inflammatory disorders of the human central nervous system.


Subject(s)
Dog Diseases/genetics , Dog Diseases/immunology , Histocompatibility Antigens Class I/genetics , Meningoencephalitis/veterinary , Multiple Sclerosis/genetics , Multiple Sclerosis/immunology , Alleles , Animals , Base Sequence , DNA Primers/genetics , Disease Models, Animal , Dogs , Exons , Female , Gene Frequency , Genes, MHC Class II , Genetic Predisposition to Disease , Genome-Wide Association Study , Haplotypes , Humans , Male , Meningoencephalitis/genetics , Meningoencephalitis/immunology , Microsatellite Repeats , Species Specificity
11.
Osteoarthritis Cartilage ; 17(11): 1453-60, 2009 Nov.
Article in English | MEDLINE | ID: mdl-19481622

ABSTRACT

OBJECTIVES: To determine the ability of radiographic bone texture (BTX) parameters to quantify subchondral tibia sclerosis and to examine clinical relevance for assessing osteoarthritis (OA) progression. We examined the relationship between BTX parameters and each of (1) location-specific joint space width (JSW) [JSW(x)] and minimum JSW (mJSW) of the affected compartment, and (2) knee alignment (KA) angle in knee radiographs of participants undergoing total knee arthroplasty (TKA). DESIGN: Digitized fixed-flexion knee radiographs were analyzed for run-length and topological BTX parameters in a subchondral region using an algorithm. Medial JSW(x) was computed at x=0.200, 0.225, 0.250 and 0.275 according to a coordinate system defined by anatomic landmarks. mJSW was determined for medial and lateral compartment lesions. KA angles were determined from radiographs using an anatomic landmark-guided algorithm. JSW measures and the magnitude of knee malalignment were each correlated with BTX parameters. Reproducibility of BTX parameters was measured by root-mean square coefficients of variation (RMSCV%). RESULTS: Run-length BTX parameters were highly reproducible (RMSCV%<1%) while topological parameters showed poorer reproducibility (>5%). In TKA participants (17 women, 13 men; age: 66+/-9 years; body mass index (BMI): 31+/-6 kg m(-2); WOMAC: 41.5+/-16.1; Kellgren-Lawrence score mode: 4), reduced trabecular spacing (Tb.Sp) and increased free ends (FE) were correlated with decreased JSW after accounting for BMI, gender and knee malalignment. These relationships were dependent on site of JSW measurement. CONCLUSION: High reproducibility in quantifying bone sclerosis using Tb.Sp and its significant relationship with JSW demonstrated potential for assessing OA progression. Increased trabecular FE and reduced porosity observed with smaller JSW suggest collapsing subchondral bone or trabecular plate perforation in advanced knee OA.


Subject(s)
Bone Density/physiology , Cartilage, Articular/pathology , Knee Joint/pathology , Osteoarthritis, Knee/pathology , Tibia/pathology , Aged , Disease Progression , Female , Humans , Knee Joint/diagnostic imaging , Male , Middle Aged , Osteoarthritis, Knee/diagnostic imaging , Radiography , Reproducibility of Results , Sclerosis/diagnostic imaging , Sclerosis/pathology , Tibia/diagnostic imaging
12.
Anim Genet ; 40(4): 569-71, 2009 Aug.
Article in English | MEDLINE | ID: mdl-19392818

ABSTRACT

DOGSET is an online resource that provides access to primer sequences that have been computationally mined from the reference genome using heuristic algorithms. The electronic repository includes PCR primers corresponding to 32,135 markers for genetic mapping and 334,657 sequence-tagged gene elements for targeted re-sequencing and mutation discovery. A customized report that tailors primer design to wet bench protocols can be exported for a region of interest by specifying genome coordinates in a graphical user interface.


Subject(s)
Chromosome Mapping , DNA Primers , Dogs/genetics , Sequence Analysis, DNA , Software , Animals , Internet , Microsatellite Repeats
13.
Osteoarthritis Cartilage ; 17(5): 579-85, 2009 May.
Article in English | MEDLINE | ID: mdl-19027328

ABSTRACT

OBJECTIVES: (1) To investigate the reproducibility of computer-assisted measurements of knee alignment angle (KA) from digitized radiographs of osteoarthritis (OA) participants requiring total knee arthroplasty (TKA) and (2) to determine whether landmark choice affects the precision of KA measurements on radiographs. METHODS: Using a custom algorithm, femoral, central, and tibial measurement-guiding rules were interactively placed on digitized posteroanterior fixed-flexion knee radiographs by mouse control and positioned according to different anatomic landmarks. The angle subtended by lines connecting these guiding rules was measured by three readers to assess interobserver, intraobserver and experience-inexperience reproducibility. Test-retest reproducibility was evaluated with duplicate radiographs from a healthy cohort. Reproducibility was assessed using root-mean square coefficients of variation (RMSCV%). The Bland-Altman method was performed on data obtained from varying anatomic landmarks (confidence interval, CI= 95%). RESULTS: From 16 healthy and 30 TKA participants, reproducibility analyses revealed a high degree of intraobserver (n=38, RMSCV=0.56%), interobserver (n=38, RMSCV=0.72%), test-retest (n=16, RMSCV=0.87%) and experience-inexperience (n=38, RMSCV=0.73%) reproducibility with variances below 1%. Varying the orientation of tibial and femoral rules according to anatomic landmarks produced a difference that exceeded an a priori limit of agreement of -1.11 degrees to +1.67 degrees. CONCLUSION: Our custom-designed software provides a robust method for measuring KAs within digitized knee radiographs. Although test-retest analyses were only performed in a healthy cohort, we anticipate a similar degree of reproducibility in an OA sample. A standardized set of anatomic landmarks employed for KA measurement is recommended since arbitrary selection of landmarks resulted in imprecise KA measurement even with a computer-assisted technique.


Subject(s)
Knee Joint/diagnostic imaging , Osteoarthritis, Knee/diagnostic imaging , Range of Motion, Articular/physiology , Adult , Arthroplasty, Replacement, Knee , Female , Humans , Image Processing, Computer-Assisted , Knee Joint/anatomy & histology , Male , Osteoarthritis, Knee/physiopathology , Radiography , Reproducibility of Results
14.
IEEE Trans Biomed Circuits Syst ; 2(4): 280-8, 2008 Dec.
Article in English | MEDLINE | ID: mdl-23853131

ABSTRACT

A micro-power CMOS front-end, consisting of a transimpedance amplifier (TIA) and an ultralow cutoff frequency lowpass filter for the acquisition of photoplethysmographic signal (PPG) is presented. Robust DC photocurrent rejection for the pulsed signal source is achieved through a sample-and-hold stage in the feed-forward signal path and an error amplifier in the feedback path. Ultra-low cutoff frequency of the filter is achieved with a proposed technique that incorporates a pair of current-steering transistors that increases the effective filter capacitance. The design was realized in a 0.35-mum CMOS technology. It consumes 600 muW at 2.5 V, rejects DC photocurrent ranged from 100 nA to 53.6 muA, and achieves lower-band and upper-band - 3-dB cutoff frequencies of 0.46 and 2.8 Hz, respectively.

15.
Hum Mol Genet ; 15(21): 3195-205, 2006 Nov 01.
Article in English | MEDLINE | ID: mdl-17000707

ABSTRACT

CD28, CTLA4 (cytotoxic T lymphocyte-associated protein 4) and ICOS (inducible T cell co-stimulator) are good candidate genes for systemic lupus erythematosus (SLE) because of their role in regulating T cell activation. CTLA4 inhibits CD28-mediated T cell activation. CTLA4 is expressed on CD4+ and CD8+ activated T cells, and also B cells, but CD28 and ICOS are largely restricted to T cells. An interval encompassing the CD28-CTLA4-ICOS locus on chromosome 2q33 was linked to lupus in two genome-wide linkage scans. This large family-based association study in 532 UK SLE families represents the first high-density genetic screen of 80 SNPs at this locus. There are seven haplotype blocks across the locus. In CTLA4, the strongest signal comes from two variants, located 2.1 kb downstream from the 3'-UTR. These polymorphisms, rs231726 (SNP 43) and rs231726 (SNP 44), are in complete linkage disequilibrium (LD) (r(2)=1) and are associated with SLE P=0.0008 (GH) and P=0.01 (family-based association test). There is also a signal in the distal 3' flanking region of CTLA4/ICOS promoter (P=0.003). There was no confirmation of published associations for SLE in the promoter or coding region of CTLA4. These SLE risk alleles are more distal than those identified in Graves' disease and are in LD with Graves' disease protective alleles identified in both of these regions of CTLA4 (Ueda et al. 2003). These factors suggest an SLE-specific pattern of association. The functional consequences of the associated polymorphisms are likely to influence CTLA4 expression, although it is possible that genetically modulated ICOS expression is involved in SLE susceptibility.


Subject(s)
Antigens, CD/genetics , Antigens, Differentiation/genetics , Lupus Erythematosus, Systemic/genetics , 3' Flanking Region , Antigens, Differentiation, T-Lymphocyte/genetics , Base Sequence , CD28 Antigens/genetics , CTLA-4 Antigen , Chromosome Mapping , Family , Female , Gene Frequency , Genetic Markers , Haplotypes , Humans , Inducible T-Cell Co-Stimulator Protein , Male , Molecular Sequence Data , Multigene Family , Polymorphism, Single Nucleotide
16.
Oncogene ; 25(16): 2304-17, 2006 Apr 13.
Article in English | MEDLINE | ID: mdl-16331265

ABSTRACT

Peroxisome proliferator-activated receptor gamma (PPARgamma) agonists demonstrate antitumor activity likely through transactivating genes that regulate cell proliferation, apoptosis, and differentiation. The PAX8/PPARgamma fusion oncogene, which is common in human follicular thyroid carcinomas appears to act via dominant negative suppression of wild-type PPARgamma, suggesting that it may be a tumor suppressor gene in thyroid cells. We have identified a novel high-affinity PPARgamma agonist (RS5444) that is dependent upon PPARgamma for its biological activity. This is the first report of this molecule and its antitumor activity. In vitro, the IC50 for growth inhibition is approximately 0.8 nM while anaplastic thyroid carcinoma (ATC) tumor growth was inhibited three- to fourfold in nude mice. siRNA against PPARgamma and a pharmacological antagonist demonstrated that functional PPARgamma was required for growth inhibitory activity of RS5444. RS5444 upregulated the cell cycle kinase inhibitor, p21WAF1/CIP1. Silencing p21WAF1/CIP1 rendered cells insensitive to RS5444. RS5444 plus paclitaxel demonstrated additive antiproliferative activity in cell culture and minimal ATC tumor growth in vivo. RS5444 did not induce apoptosis but combined with paclitaxel, doubled the apoptotic index compared to that of paclitaxel. Our data indicate that functional PPARgamma is a molecular target for therapy in ATC. We demonstrated that RS5444, a thiazolidinedione (Tzd) derivative, alone or in combination with paclitaxel, may provide therapeutic benefit to patients diagnosed with ATC.


Subject(s)
Antineoplastic Agents/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cyclin-Dependent Kinase Inhibitor p21/physiology , PPAR gamma/agonists , Paclitaxel/administration & dosage , Thiazolidinediones/therapeutic use , Thyroid Neoplasms/drug therapy , Angiogenesis Inhibitors/therapeutic use , Animals , Cell Line, Tumor , Cell Proliferation/drug effects , Chromans/pharmacology , Cyclin-Dependent Kinase Inhibitor Proteins/biosynthesis , Female , Humans , Mice , PPAR gamma/physiology , Thiazolidinediones/administration & dosage , Thiazolidinediones/pharmacology , Thyroid Neoplasms/pathology , Troglitazone
17.
Singapore Med J ; 45(11): 520-4, 2004 Nov.
Article in English | MEDLINE | ID: mdl-15510323

ABSTRACT

INTRODUCTION: Hypertension is highly prevalent among continuous ambulatory peritoneal dialysis (CAPD) patients and is a major risk factor for cardiovascular complications. This study examines the risk factors associated with poorly-controlled hypertension in CAPD. METHODS: We performed a cross-sectional study of 66 stable adult CAPD patients to evaluate their hypertension control over a period of three to four months and their associations with other clinical and laboratory parameters. RESULTS: The mean age of the patients was 56.7 (plus or minus 1.27) years. Their mean systolic and diastolic blood pressure were 139 (plus or minus 2.59) mmHg and 77 (plus or minus 1.35) mmHg respectively; 71 percent of them were on antihypertensive drugs. Thirty (45.5 percent) patients had high blood pressure greater than 140/90mmHg. Compared with patients with normal blood pressure, patients with high blood pressure received significantly more antihypertensive drugs (p-value equals 0.034) and were more likely to be clinically overloaded (p-value less than 0.001). Multivariate analysis showed that systolic blood pressure was predicted by volume expansion (p-value less than 0.001) while diastolic blood pressure was negatively predicted by age (p-value equals to 0.004). In addition, volume overload was predicted positively by dialysate/plasma creatinine (p-value equals 0.011) and negatively by serum albumin (p-value less than 0.001). CONCLUSION: Clinically-apparent volume overload was associated with poor systolic blood pressure control despite aggressive antihypertensive drug therapy. This finding underlines the importance of fluid control and could provide an explanation of the poor outcome observed in patients with high peritoneal transport.


Subject(s)
Blood Volume/drug effects , Hypertension/drug therapy , Hypertension/physiopathology , Kidney Failure, Chronic/therapy , Peritoneal Dialysis, Continuous Ambulatory , Adult , Antihypertensive Agents/administration & dosage , Antihypertensive Agents/therapeutic use , Cross-Sectional Studies , Diet, Sodium-Restricted/statistics & numerical data , Female , Humans , Hypertension/etiology , Kidney Failure, Chronic/complications , Male , Middle Aged , Patient Compliance , Risk Factors , Risk-Taking
18.
Br J Ophthalmol ; 88(8): 995-7, 2004 Aug.
Article in English | MEDLINE | ID: mdl-15258011

ABSTRACT

BACKGROUND: Mitomycin C (MMC) and limbal conjunctival autograft (LCAU) are two known useful adjuvants in the prevention of pterygial recurrence. This study was conducted to compare the outcome of these two treatments. METHODS: Prospective study on consecutive cases of primary pterygium (February 2001 to March 2002) randomised into two adjuvant groups: (1) intraoperative 0.02% MMC for 5 minutes or (2) LCAU. Patients were followed for recurrence (defined as fibrovascular tissue invading the cornea >1.5mm) and complications for a period of one year. RESULTS: 115 eyes in 114 patients who completed the study were randomised to receive MMC (n = 63) and LCAU (n = 52). There were 10 recurrences (15.9%) in the MMC group and only one recurrence (1.9%) in the LCAU group. There was a statistically significant difference in the recurrence rate between the two groups (p = 0.04). There were a total of three conjunctival cysts, three symblephara, one granuloma, and one dellen. No other visually significant complications were encountered in either group. CONCLUSION: Although LCAU resulted in better one year success rates, it is technically more difficult and inapplicable in cases with previous limbal disturbance. Simple excision followed by MMC or LCAU are both safe and acceptable adjuvants for pterygium excision. Choice of adjuvant should be carefully made based on assessment of recurrence risk, local practices, and surgeon's expertise.


Subject(s)
Alkylating Agents/therapeutic use , Conjunctiva/transplantation , Mitomycin/therapeutic use , Pterygium/drug therapy , Pterygium/surgery , Adult , Aged , Aged, 80 and over , Alkylating Agents/adverse effects , Combined Modality Therapy , Female , Humans , Male , Middle Aged , Mitomycin/adverse effects , Postoperative Complications/etiology , Prospective Studies , Recurrence
19.
Singapore Med J ; 44(2): 74-8, 2003 Feb.
Article in English | MEDLINE | ID: mdl-14503780

ABSTRACT

OBJECTIVE: The efficacy of short-course triple eradication therapy has been documented in patients with Helicobacter pylori infection and normal renal function. We have evaluated a one-week proton-pump inhibitor-based triple therapy for Helicobacter pylori eradication in a retrospective review of patients with chronic renal failure. METHODS: We studied 25 patients (mean age 65.1 +/- 2.4 years) with creatinine clearance <30 ml/min/1.73 m2 or serum creatinine level >200 micromol/L (13 on dialysis), who had Helicobacter pylori infection, documented by histological examination or rapid urease test, together with either peptic ulcer disease or severe gastritis. The combination of Omeprazole 20 mg BID or Lansoprazole 30 mg BID, amoxicillin 1 gm BID and clarithromycin 500 mg BID was given for one week, in addition to therapy for peptic ulcers. All patients were re-endoscoped four weeks later. RESULTS: All but one patient (96%) had successful eradication. On repeat endoscopy, all 13 patients with peptic ulcers had healed ulcers. For the 12 gastritis patients, three became normal and nine had persistent gastritis. For patients not on dialysis, the serum creatinine level and creatinine clearance remained stable at two weeks after treatment (303 +/- 37 vs. 330 +/- 36 micromol/l, p=ns; 23.6 +/- 3.4 vs. 26.0 +/- 3.9 ml/min/1.73 m2, p=ns, respectively). CONCLUSION: The short course triple therapy was highly efficacious for Helicobacter pylori eradication in patients with chronic renal failure, with no adverse effect on renal function.


Subject(s)
Amoxicillin/therapeutic use , Anti-Ulcer Agents/therapeutic use , Clarithromycin/therapeutic use , Drug Therapy, Combination/therapeutic use , Gastritis/drug therapy , Helicobacter Infections/drug therapy , Helicobacter pylori/drug effects , Kidney Failure, Chronic/complications , Omeprazole/therapeutic use , Penicillins/therapeutic use , Peptic Ulcer/drug therapy , Aged , Amoxicillin/administration & dosage , Amoxicillin/adverse effects , Anti-Ulcer Agents/administration & dosage , Anti-Ulcer Agents/adverse effects , Clarithromycin/administration & dosage , Clarithromycin/adverse effects , Creatinine/blood , Drug Therapy, Combination/administration & dosage , Drug Therapy, Combination/adverse effects , Endoscopy, Gastrointestinal , Female , Gastritis/complications , Humans , Kidney Failure, Chronic/microbiology , Male , Middle Aged , Omeprazole/administration & dosage , Omeprazole/adverse effects , Penicillins/administration & dosage , Penicillins/adverse effects , Peptic Ulcer/complications , Retrospective Studies
20.
Hong Kong Med J ; 8(3): 202-6, 2002 Jun.
Article in English | MEDLINE | ID: mdl-12055367

ABSTRACT

We report on a middle-aged man with end-stage renal failure apparently secondary to recurrent renal stones. He developed systemic oxalosis soon after commencing dialysis. The diagnosis of primary hyperoxaluria type 1 was supported by the finding of high dialysate glycolate excretion. The patient subsequently received an isolated cadaveric renal transplant, but the outcome was a rapid recurrence of oxalosis and early graft failure. Although isolated liver or renal transplantation in addition to various adjuvant measures may be considered in the early stage, combined liver-kidney transplantation remains the only definitive therapy for a patient with end-stage renal failure and systemic oxalosis due to hyperoxaluria type 1. This case illustrates the possible late presentation of primary hyperoxaluria type 1 and the poor outcome with isolated renal transplantation after the development of systemic oxalosis. One should thus have a high index of suspicion in patients with recurrent renal stones of this rare, but nevertheless important, entity.


Subject(s)
Hyperoxaluria, Primary/complications , Kidney Calculi/etiology , Humans , Hyperoxaluria, Primary/diagnosis , Hyperoxaluria, Primary/pathology , Kidney/pathology , Kidney Calculi/surgery , Kidney Failure, Chronic/etiology , Kidney Transplantation , Male , Middle Aged , Recurrence , Renal Dialysis , Transplantation, Homologous
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