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Biomedical subjects

D Chan

Publications and source records attributed to D Chan.

At least 37 records · Page 2Linked to original sources
PubMed2004

EEG abnormalities in frontotemporal lobar degeneration.

The EEG appearances in patients with frontotemporal lobar degeneration (FTLD) were compared with those in patients with Alzheimer disease (AD). EEG abnormalities were found in 61% of FTLD patients, with the degree of EEG abnormality increasing with dementia severity. There was no significant difference in the severity of EEG abnormality between the FTLD and AD patient groups. These data suggest a need for reappraisal of the role of the EEG in the diagnostic differentiation of FTLD from AD.

Alpha Rhythm↗
PubMed2004

Socio-economic deprivation and excess winter mortality and emergency hospital admissions in the South Yorkshire Coalfields Health Action Zone, UK.

The aims of this study were to describe the pattern of excess winter mortality and emergency hospital admissions in the South Yorkshire Coalfields Health Action Zone, and to examine the relationship between excess winter mortality and emergency hospital admissions and socio-economic deprivation at the enumeration district level. We analysed monthly deaths from 1981 to 1999 and monthly emergency hospital admissions from 1990 to 1999 for cardiovascular disease, respiratory disease and all other causes of death for people aged 45 years and above. We used the enumeration district level Townsend socio-economic deprivation score to categorize enumeration districts by quintile. Excess winter mortality ratios (observed/expected) for females and males, respectively, were 1.70 and 1.58 for respiratory disease, 1.25 and 1.20 for cardiovascular disease, and 1.09 and 1.07 for all other causes of death. The excess winter hospital admission ratio for respiratory disease was 1.80 for females and 1.58 for males. No excess was evident for the other two groups of conditions. We found no significant increase in excess winter mortality ratios with increasing socio-economic deprivation. There was also no significant increase in the excess winter respiratory admission ratio with increasing deprivation. With regard to age, we found P<0.0001 and for all other diseases P>0.001 and also in the excess winter hospital admission ratio for respiratory disease P<0.0001 With regard to sex, the excess ratios were lower in men than in women for both respiratory mortality P<0.05 and respiratory hospital admissions P<0.0001 We also observed that excess winter mortality ratios decreased significantly over the 18-year period for cardiovascular disease P<0.05 and for all other diseases P<0.05. Our results suggest that measures to reduce excess winter mortality should be implemented on a population-wide basis and not limited to socio-economically deprived areas. There may also be a case for tailoring interventions to specifically meet the needs of older people.

Aged↗
PubMed2004

Survey of ochratoxin A and deoxynivalenol in stored grains from the 1999 harvest in the UK.

Three hundred and twenty samples from the 1999 UK harvest comprising wheat (201 samples), barley (106) and oats (13) were analysed for ochratoxin A and deoxynivalenol. A small number of organic samples was also obtained. Samples were collected from farms, central stores, mills, maltings and ports from across the UK from February to April 2000. Ochratoxin A and deoxynivalenol analysis was by affinity column clean up and high-performance liquid chromatography with fluorescence and ultraviolet light detection, respectively, with limits of detection of 0.2 and 20 microg kg(-1). The survey found ochratoxin A at below 5 microg kg(-1) in 97% of the samples indicating satisfactory storage conditions. The remaining 3% of the samples contained ochratoxin A at levels between 5.2 and 231 microg kg(-1), but none of these samples was intended for human consumption. Deoxynivalenol was detected in 88% of all samples, with 83% below 100 microg kg(-1); the maximum level was 600 microg kg(-1). Twenty samples containing deoxynivalenol at or above 150 microg kg(-1) by high-performance liquid chromatography were all confirmed by gas chromatography/mass spectrometry. Nivalenol was also detected by gas chromatography/mass spectrometry at levels of 50 microg kg(-1) or higher in 18 of 20 samples where deoxynivalenol was confirmed.

Chromatography, High Pressure Liquid↗
PubMed2003

A dose- and schedule-finding study of darbepoetin alpha for the treatment of chronic anaemia of cancer.

A multicentre study evaluated the efficacy and safety of darbepoetin alpha administered weekly (QW), every 3 weeks (Q3W), and every 4 weeks (Q4W) to anaemic patients with cancer not concurrently receiving chemotherapy or radiotherapy. The QW portion (n=102) was an open-label, sequential, dose-escalation design; cohorts received darbepoetin alpha QW by subcutaneous (s.c.) injection at 0.5, 1.0, 2.25, or 4.5 micro g kg(-1) week(-1) for 12 weeks. The 12-week placebo-controlled, double-blind Q3W (6.75 micro g kg(-1)) and Q4W (6.75 or 10.0 micro g kg(-1)) schedules (n=86), which enrolled different patients, took place after the QW schedule and were followed by a 12-week, open-label phase. Patients were evaluated for change in haemoglobin end points and red blood cell transfusions, serum darbepoetin alpha concentration, and safety. Selected domains of health-related quality of life (HRQOL) were measured. With QW dosing, at least 70% of each cohort had a haemoglobin increase from baseline of > or =2 g dl(-1) or a concentration > or =12 g dl(-1) (haematopoietic response). In the 4.5 micro g kg(-1) QW cohort, all patients achieved a haematopoietic response (100%; 95% confidence interval (CI)=100, 100). In the Q3W and Q4W schedules, all cohorts had at least 60% of patients who achieved a haematopoietic response. Darbepoetin alpha effectively increases haemoglobin concentration when given QW, Q3W, or Q4W. Less-frequent administration may benefit patients with chronic anaemia of cancer and their caregivers alike.

Aged↗
PubMed2003

Transformation induced by Ewing's sarcoma associated EWS/FLI-1 is suppressed by KRAB/FLI-1.

Ewing's sarcoma is a childhood bone tumour with poor prognosis, most commonly associated with a t(11;22)(q24;q12) reciprocal translocation that fuses the EWS and FLI-1 genes, resulting in the production of an aberrant chimeric transcription factor EWS/FLI-1. To elucidate the mechanisms by which EWS/FLI-1 mediates transformation in mouse models, we have generated a murine Ews/Fli-1 fusion protein. We demonstrate that this protein transforms fibroblast cells in vitro similar to human EWS/FLI-1 as demonstrated by serum and anchorage-independent growth, the formation of tumours in nude mice and elevation of the oncogenic marker c-myc. Furthermore, transformation of these cells was inhibited by a specific repressor, KRAB/FLI-1. The KRAB/FLI-1 repressor also suppressed the tumorigenic phenotype of a human Ewing's sarcoma cell line. These findings suggest that the transformed phenotype of Ewing's sarcoma cells can be reversed by using the sequence-specific FLI-1-DNA-binding domain to target a gene repressor domain. The inhibition of EWS/FLI-1 is the first demonstration of the KRAB domain suppressing the action of an ETS factor. This approach provides potential avenues for the elucidation of the biological mechanisms of EWS/FLI-1 oncogenesis and the development of novel therapeutic strategies.

3T3 Cells↗
PubMed2003

The effects of obesity on pulmonary function.

AIMS: (1) To determine the predominant pulmonary function abnormality in our population of obese children; and (2) to assess the correlation between the severity of lung function impairment and the degree of obesity as assessed by dual energy x ray absorptiometry (DEXA). METHODS: Sixty four obese patients underwent physical examination, standardised pulmonary function tests (spirometry, lung volumes, and single breath diffusion capacity for carbon monoxide), and DEXA scan measurements. The trunk and subtotal (total - head) body fat mass were used as surrogate index of body adiposity. RESULTS: Sixteen girls and 48 boys with median age and body mass index (BMI) of 12 years (interquartile range (IQR): 10-14) and 30.1 kg/m2 (IQR: 27.2-32.8) respectively were studied. None of the patients had clinical evidence of cardiopulmonary disease. Reduction in functional residual capacity (median FRC 93% predicted, IQR: 68.5-116.5%) and impairment of diffusion capacity (median DLco 83.5% predicted, IQR: 70.0-100.7%) were the most common abnormalities in our cohort, being observed in 30 (46%) and 21 (33%) patients respectively. Obstructive ventilatory impairment was found in three patients. There was significant negative correlation between the degree of reduction of FRC but not DLco with DEXA scan measurements, but such a relation was not found when BMI was used as the indicator of obesity. CONCLUSION: Reduction in FRC and diffusion impairment were the commonest abnormalities found in our cohort of obese patients. Reduction in static lung volume was correlated with the degree of obesity.

Absorptiometry, Photon↗
PubMed2003

Sleeping energy expenditure in paediatric patients with obstructive sleep apnoea syndrome.

OBJECTIVE: To investigate sleeping energy expenditure in paediatric patients with obstructive sleep apnoea syndrome. DESIGN: Retrospective study. Setting. University teaching hospital, Hong Kong. PATIENTS AND METHODS: A retrospective analysis comparing sleeping energy expenditure in patients with confirmed obstructive sleep apnoea syndrome and control subjects matched for age, sex, and ideal weight for body height. Subjects were recruited from the Paediatric Chest Clinic and all had undergone overnight polysomnography and sleeping energy expenditure measurement by open-circuit indirect calorimetry using a metabolic cart and canopy system. The measurements were taken during slow-wave sleep. RESULTS: Twenty-four cases with obstructive sleep apnoea syndrome (apnoea hypopnoea index >5) and 23 control subjects were studied. Mean age and ideal weight for body height were 9.4 (standard deviation, 3.9) years and 152.5% (27.2%), respectively. Mean sleeping energy expenditure corrected for body weight for the cases and the control group were 44.83 (standard deviation, 10.49) Kcal/day and 40.71 (10.60) Kcal/day, respectively. Sleeping energy expenditure was not found to be associated with the severity of obstructive sleep apnoea syndrome (r=0.34, P=0.27). CONCLUSION: A trend towards greater sleeping energy expenditure was found in patients with obstructive sleep apnoea syndrome. Further studies on the metabolic aspects of this condition are required.

Calorimetry, Indirect↗
PubMed2002

Hydration dynamics of human fingernails: an ellipsometric study.

We use spectroscopic ellipsometry to obtain the complex refractive index, ñ=n+ik, of human fingernails. By studying the change of ñ upon hydration and dehydration, we reveal three different time domains with typical time constants of 4, 150, and 3200 min. A simple model that takes into account the presence of one fast and one slow process is fully consistent with the observed hydration and dehydration dynamics. We attribute these processes to "free" water incorporated between the keratin filaments and water more tightly "bound" in keratin complexes, respectively. From our model we determine the hydration profiles of "free" and "bound" water during, both, hydration and dehydration.

Chemical Phenomena↗
PubMed2002

Epilepsy presenting as AD: neuroimaging, electroclinical features, and response to treatment.

Three patients with progressive memory impairment initially attributed to AD underwent serial neuropsychometry, MRI, and EEG. Registered serial MRI volumetric analysis showed no loss of whole or regional brain volume. EEG revealed temporal lobe spike activity and antiepileptic treatment was optimized. Memory functions improved with antiepileptic medication in all three patients. The demonstration of temporal lobe spike activity in patients with progressive memory impairment is an indication for a trial of antiepileptic medication.

Aged↗
PubMed2002

Recipients in need of ancillary services and their receipt of HIV medical care in California.

For many individuals with access to quality medical care, HIV disease is no longer a critical short term illness but a chronic condition giving rise to more clients requiring ongoing medical care. Programs funded by the federal Ryan White Comprehensive AIDS Resources Emergency Act not only provide essential medical care for these individuals but also facilitate access to medical care services. These programmes fund services, including case management, transportation, and translation assistance, that feature ongoing assistance and enable individuals to remain in the health care system. Because of the importance of maintaining the strict drug regimen, retention in care is also an important part of the overall HIV care component. This study analyzed the relationship of ancillary services and a federal health programme client's receipt of medical care and retention in the health care system. We defined a cohort in need of ancillary services in part by a questionnaire designed to identify factors relating to need. These factors included education, language, and substance use. By merging client level data files we were able to identify medical service utilization trends among the individuals in the cohort who received a high number of ancillary services (more than 11 ancillary service visits in the two-year study period, n = 138) and those who received few services (fewer than six ancillary service visits in the two-year study period, n = 132). Results suggest that the receipt of ancillary services is associated with receipt of and retention in primary medical care. We found that for federal health programme clients in need of ancillary services, a positive relationship existed between their receipt of ancillary services and their access to primary medical care (p </= 0.001). This observation held constant when age, race, gender, and insurance coverage were controlled for. Also, these clients were more likely to be seen by a medical doctor at least once in three consecutive six-month periods when they received needed ancillary services (p </= 0.01).

Adult↗
PubMed2002

Respiratory function in patients with thalassaemia major: relation with iron overload.

AIMS: (1) To determine the pattern of respiratory impairment in children with thalassaemia major (TM); (2) to assess the relation between the degree of respiratory impairment and total body iron content. METHODS: Twenty nine TM patients were recruited. All underwent physical examination, standardised pulmonary function tests (spirometry, lung volume, and single breath diffusion capacity for carbon monoxide), and magnetic resonance imaging measurements of the liver. Serum ferritin was measured. The signal intensity ratio of liver to that of paraspinal muscle (T1 weighted sequence) and serum ferritin were used as surrogate index of body iron content. RESULTS: Sixteen boys and 13 girls (median age 14.2 years) were studied. None had clinical evidence of congestive heart failure. Sixteen had normal lung function. Impairment of diffusion capacity (median DL(co) 83.5% predicted) was the most common abnormality, being observed in 34% of patients. Pure restrictive and obstructive ventilatory impairment was found in one and two patients respectively. Five patients had a combination of ventilation and diffusion defects. There was no correlation between the degree of impairment of each respiratory abnormality and body iron content. CONCLUSION: Diffusion impairment was the commonest abnormality found in our cohort of paediatric TM patients. Our data did not support the notion that respiratory function impairment was correlated with body iron content.

Adolescent↗
PubMed2001

Rates of global and regional cerebral atrophy in AD and frontotemporal dementia.

OBJECTIVE: Serial registered MRI provides a reproducible technique for detecting progressive cerebral atrophy in vivo and was used to determine if there were differences between the rates of cerebral atrophy in AD and frontotemporal dementia (FTD). METHODS: Eighty-four patients with dementia (54 AD and 30 FTD) and 27 age-matched control subjects each had at least two volumetric MR scans. Serial scans were positionally matched (registered), and brain volume loss was determined by calculation of the brain boundary shift integral. RESULTS: There was a difference between the rates of whole-brain atrophy in patients (mean annual volume loss 2.7% of total brain volume) and in control subjects (mean annual volume loss 0.5%). AD and FTD were associated with different rates of atrophy (mean annual losses 2.4 and 3.2%). The range of atrophy rates in the FTD group (0.3 to 8.0%) greatly exceeded that in the AD group (0.5 to 4.7%). Frontal-variant FTD was associated with a wider range of atrophy rates than temporal-variant FTD. Analysis of regional brain atrophy rates revealed that there was widespread symmetrically distributed cerebral volume loss in AD, whereas in frontal FTD there was greater atrophy anteriorly and in temporal FTD the atrophy rate was greatest in the left anterior cerebral cortex. CONCLUSIONS: Both AD and FTD patients had increased rates of brain atrophy. Whereas the patients with AD were associated with a relatively restricted spread of atrophy rates, the greater spread of rates observed in the patients with FTD may reflect the heterogeneity of disease in FTD, with differences observed between frontal and temporal FTD. Increased rates of whole-brain atrophy did not discriminate AD from FTD, but analysis of regional atrophy rates revealed marked differences between patient groups.

Aged↗
PubMed2001

A dominant interference collagen X mutation disrupts hypertrophic chondrocyte pericellular matrix and glycosaminoglycan and proteoglycan distribution in transgenic mice.

Collagen X transgenic (Tg) mice displayed skeleto-hematopoietic defects in tissues derived by endochondral skeletogenesis.(1) Here we demonstrate that co-expression of the transgene product containing truncated chicken collagen X with full-length mouse collagen X in a cell-free translation system yielded chicken-mouse hybrid trimers and truncated chicken homotrimers; this indicated that the mutant could assemble with endogenous collagen X and thus had potential for dominant interference. Moreover, species-specific collagen X antibodies co-localized the transgene product with endogenous collagen X to hypertrophic cartilage in growth plates and ossification centers; proliferative chondrocytes also stained diffusely. Electron microscopy revealed a disrupted hexagonal lattice network in the hypertrophic chondrocyte pericellular matrix in Tg growth plates, as well as altered mineral deposition. Ruthenium hexamine trichloride-positive aggregates, likely glycosaminoglycans (GAGs)/proteoglycans (PGs), were also dispersed throughout the chondro-osseous junction. These defects likely resulted from transgene co-localization and dominant interference with endogenous collagen X. Moreover, altered GAG/PG distribution in growth plates of both collagen X Tg and null mice was confirmed by a paucity of staining for hyaluronan and heparan sulfate PG. A provocative hypothesis links the disruption of the collagen X pericellular network and GAG/PG decompartmentalization to the potential locus for hematopoietic failure in the collagen X mice.

Animals↗
PubMed2001

Long-term retrograde amnesia...the crucial role of the hippocampus.

For patients with hippocampal pathology, disagreement exists in the literature over whether retrograde amnesia is temporally limited or very extensive depending on whether the anatomical damage is restricted to this structure or also involves additional temporal cortex. We report a comprehensive assessment of retrograde and anterograde memory functions of a severely global amnesic patient (VC). We found that he presented with a remarkably extensive and basically ungraded retrograde amnesia. This impairment profoundly affected four decades preceding the onset of his amnesia and encompassed both non personal and personal facts and events. VC also presented with a severe anterograde amnesia and a deficit in the acquisition of new semantic knowledge in the post-morbid period. Detailed MRI volumetric measurements revealed gross abnormalities in both hippocampi which were markedly shrunken. Of relevance to the debate on retrograde amnesia were the observations that the volumes of both entorhinal cortices and the remainder of both temporal lobes were normal. These data suggest that the hippocampus is critical not only for the efficient encoding and hence normal recall of new information but also for the recall of episodic information acquired before the onset of amnesia. Our results are compatible with the view that retrograde amnesia is both extensive and ungraded when the damage is limited to the hippocampus.

Aged↗
PubMed2001

Hemostatic laparoscopic partial nephrectomy: initial experience with the radiofrequency coagulation-assisted technique.

OBJECTIVES: The techniques for hemostasis after renal tumor excision have limited the widespread application of laparoscopic partial nephrectomy (LPN). To improve hemostasis and aid visualization, we report our experience with a novel radiofrequency coagulation (RFC) technique for LPN. METHODS: Ten patients underwent RFC-assisted LPN. The demographic and perioperative data were tabulated. Patients were positioned as for laparoscopic nephrectomy, and laparoscopic ports were placed. The kidney within Gerota's fascia was mobilized, and the fat overlying the tumor was carefully removed for pathologic evaluation. Under laparoscopic guidance, a radiofrequency probe was percutaneously inserted into the lesion and deployed to coagulate the lesion and a margin of normal parenchyma. Laparoscopic scissors were used to excise the lesion; additional hemostatic maneuvers were used selectively. RESULTS: The mean renal tumor size was 2.1 cm (range 1.0 to 3.2). The median operative time was 170 minutes and the median blood loss was 125 mL. The RFC technique resulted in complete tissue coagulation within the treated volume, thereby facilitating intraoperative visualization, minimizing blood loss, and permitting rapid and controlled tumor resection. The renal architecture was preserved, allowing accurate diagnosis of renal cell carcinoma and angiomyolipoma in 9 and 1 cases, respectively. No perioperative complications occurred. CONCLUSIONS: The use of RFC is an effective method to facilitate LPN of both exophytic and endophytic masses. By coagulating a margin of normal parenchyma, the technique minimizes blood loss and improves visualization during LPN. We anticipate this technique will broaden the clinical application for LPN.

Adult↗
PubMed2001

SR48692 is a neurotensin receptor antagonist which inhibits the growth of small cell lung cancer cells.

Neurotensin (NT) is an autocrine growth factor for some small cell lung cancer (SCLC) cells. In this communication, the effects of a non-peptide NT receptor antagonist, SR48692, were investigated using SCLC cells. (3)H-SR48692 bound with high affinity (IC(50) = 20 nM) to NCI-H209 cells. Also, NT and SR48692 inhibited specific (125)I-NT binding with high affinity (IC(50) values of 2 and 200 nM). In contrast, the NT(2) receptor agonist, levocabastine, had little effect on specific (125)I-NT binding, second messenger production and proliferation using NCI-H209 cells. SR48692 (5 microM) antagonized the ability of NT (10 nM) to cause elevated cytosolic Ca2+ in Fura-2 AM loaded NCI-H209 cells. SR48692 antagonized the ability of NT to cause elevation of c-fos mRNA in these cells. Using a MTT proliferation assay, SR48692 inhibited NCI-H209 and H345 proliferation in a concentration-dependent manner. Using a clonogenic assay, 1 microM SR48692, reduced NCI-H209 colony number. Also, SR48692 (0.4 mg/kg per day) inhibited NCI-H209 xenograft proliferation in nude mice. These results suggest that SR48692 is a NT(1) receptor antagonist which inhibits SCLC growth.

Animals↗
PubMed2001

Gelatinase A (MMP-2) activation by skin fibroblasts: dependence on MT1-MMP expression and fibrillar collagen form.

The respective requirements of collagen and MT1-MMP in the activation of MMP-2 by primary fibroblast cultures were explored further. Three-dimensional gels enriched in human collagen types I and III or composed of recombinant human type II or III collagen, caused increased MT1-MMP production (mRNA and protein) and induced MMP-2 activation. Only marginal induction was seen with dried monomeric collagen confirming the need for collagen fibrillar organisation for activation. To our surprise, relatively low amounts (as low as 25 microg/ml) of acid soluble type I collagen added to fibroblast cultures also induced potent MMP-2 activation. However, the requirement for collagen fibril formation by the added collagen was indicated by the inhibition seen when the collagen was pre-incubated with a fibril-blocking peptide, and the reduced activation seen with alkali-treated collagen preparations known to have impaired fibrilisation. Pre-treatment of the collagen with sodium periodate also abrogated MMP-2 activation induction. Further evidence of the requirement for collagen fibril formation was provided by the lack of activation when type IV collagen, which does not form collagen fibrils, was added in the cultures. Fibroblasts derived from MT1-MMP-deficient mice were unable to activate MMP-2 in response to either three-dimensional collagen gel or added collagen solutions, compared to their littermate controls. Collectively, these data indicate that the fibrillar structure of collagen and MT1-MMP are essential for the MMP-2 activational response in fibroblasts.

Animals↗