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Biomedical subjects

G Dougherty

Publications and source records attributed to G Dougherty.

At least 19 recordsLinked to original sources
PubMed2001

Bone density measured by dual-energy X-ray absorptiometry in healthy Kuwaiti women.

A preliminary cross-sectional study of 623 healthy Kuwaiti women aged 20-79 years was carried out using dual-energy X-ray absorptiometry (DXA) to establish reference values of bone mineral density (BMD). Measurements were taken at the lumbar spine and proximal femur. The data were compared with normative data taken from Caucasian U.S./North European women over 6 decades of age. Our results showed the expected decline in BMD with age, especially for postmenopausal women. Despite differences in ethnicity, diet, and lifestyle no statistically significant differences in BMD were detected between the Kuwaiti subjects and the Caucasian normative data. Age-matched, clinically well-defined normative data for a given population must be used to diagnose osteoporosis and establish fracture risk. This study represents baseline data for Kuwaiti Arab females: it indicates that their BMD values are close to those of Caucasian females and higher than those reported recently for Lebanese and Saudi females. Further data is being collected to increase the statistical power of the study.

Absorptiometry, Photon↗
PubMed2001

A comparison of the texture of computed tomography and projection radiography images of vertebral trabecular bone using fractal signature and lacunarity.

The structural integrity of trabecular bone is an important factor characterizing the biomechanical strength of the vertebra, and is determined by the connectivity of the bone network and the trabeculation pattern. These can be assessed using texture measures such as the fractal signature and lacunarity from a high resolution projection radiograph. Using central sections of lumbar vertebrae we compared the results obtained from high-resolution transverse projection images with those obtained from spatially registered low-resolution images from a conventional clinical CT scanner to determine whether clinical CT data can provide useful structural information. Provided the power spectra of the CT images are corrected for image system blurring, the resulting fractal signature is similar for both modalities. Although the CT images are blurred relative to the projection images, with a consequent reduction in lacunarity, the estimated trabecular separation obtained from the lacunarity plots is similar for both modalities. This suggests that these texture measures contain essential information on trabecular microarchitecture, which is present even in low resolution CT images. Such quantitative texture measurements from CT or MRI images are potentially useful in monitoring bone strength and predicting future fracture risk.

Biomechanical Phenomena↗
PubMed2001

Fractal signature and lacunarity in the measurement of the texture of trabecular bone in clinical CT images.

Fractal analysis is a method of characterizing complex shapes such as the trabecular structure of bone. Numerous algorithms for estimating fractal dimension have been described, but the Fourier power spectrum method is particularly applicable to self-affine fractals, and facilitates corrections for the effects of noise and blurring in an image. We found that it provided accurate estimates of fractal dimension for synthesized fractal images. For natural texture images fractality is limited to a range of scales, and the fractal dimension as a function of spatial frequency presents as a fractal signature. We found that the fractal signature was more successful at discriminating between these textures than either the global fractal dimension or other metrics such as the mean width and root-mean-square width of the spectral density plots. Different natural textures were also readily distinguishable using lacunarity plots, which explicitly characterize the average size and spatial organization of structural sub-units within an image. The fractal signatures of small regions of interest (32x32 pixels), computed in the frequency domain after corrections for imaging system noise and MTF, were able to characterize the texture of vertebral trabecular bone in CT images. Even small differences in texture due to acquisition slice thickness resulted in measurably different fractal signatures. These differences were also readily apparent in lacunarity plots, which indicated that a slice thickness of 1 mm or less is necessary if essential architectural information is not to be lost. Since lacunarity measures gap size and is not predicated on fractality, it may be particularly useful for characterizing the texture of trabecular bone.

Adult↗
PubMed2000

Effect of sub-pixel misregistration on the determination of the point spread function of a CT imaging system.

The point spread function (PSF) of an imaging system provides a complete, quantitative description of its resolution. In computed tomography (CT) it can be obtained conveniently and directly from the image of a thin metal wire. However, the shape of the observed PSF is affected by arbitrary sub-pixel shifts in alignment between the wire object and the imaging raster, causing partial volume averaging. We investigated the loss of symmetry of the PSF due to this misregistration, using a thin wire at a small angle to the axis of the CT scanner. We were able to identify the optimal registration, and hence the best estimate of the PSF, from the minimum skewness of a series of images. Determination of an exact PSF is important in the imaging of structures of sub-pixel size, such as small blood vessels or trabeculae in spongy bone. The method is particularly useful for modalities with coarse rasters such as magnetic resonance imaging and nuclear medicine.

Algorithms↗
PubMed2000

The peak CT number of profiles perpendicular to the vertebral cortical shell may be a useful indicator of the integrity of the cortical shell.

Limited spatial resolution affects the ability of clinical CT systems to directly measure the thickness and density of the vertebral cortical shell. In such cases the peak CT number (CTp) of a profile through the cortical shell is approximately proportional to the product of thickness and density and hence an average of several of these values (CTp) may be useful as an indicator of the integrity of the cortical shell. Values of CTp were determined around the anterior two-thirds of the cortical shell of the L3 and L4 lumbar vertebrae of 96 Kuwaiti women (mean age+/-SD=50.0+/-8.5). There was no significant difference between the two vertebrae in terms of CTp and trabecular BMD values. There was a significant correlation between CTp and trabecular BMD for each vertebra (r=0.597, p<0.0001), and between CTp and patient age (r=0.624, p<0.001), suggesting that both cortical and trabecular bone may be subject to similar thinning mechanisms during ageing and osteoporosis. The variation of CTp around the cortical shell, represented by the standard deviation of nine CTp measurements, was significantly correlated with the mean value (r=0.503, p<0.0001) and may be useful as a descriptor of cortical structure.

Adult↗
PubMed2000

A quantitative index for the measurement of the tortuosity of blood vessels.

We propose a novel index for quantitating arterial tortuosity, based on second differences of the coordinates of the vessel midline. The index is independent of the magnification of the image and of sampling frequency. We have demonstrated its validity as an indicator of changes in morphology using simulated shapes. It is superior to two other putative indices based on vessel elongation and the variance of differences in the vessel midline coordinates, presented previously in the literature. The proposed index is easily generalised to three dimensions, allowing a true three-dimensional tortuosity index to be calculated from biplane angiograms or serial tomographic slices. It has a number of clinical applications. Preliminary data, using 82 aortograms from radiographic archives, showed a significant correlation between the tortuosity of the abdominal aorta and subject age (r=0.684, P<0.001). For this group, increased tortuosity was especially evident for subjects above 40 yr of age.

Adult↗
PubMed1999

Measurement of thickness and density of thin structures by computed tomography: a simulation study.

The limited spatial resolution of clinical CT systems causes difficulties in the measurement of the density and thickness of thin structures such as the vertebral cortical shell. We simulated the imaging process by convolving experimentally determined point spread functions with rectangular and Gaussian profiles, for various fields of view or pixel sizes and reconstruction kernels. The simulations successfully explained the reported overestimation of thickness and underestimation of density when imaging thin structures. Both effects are larger for Gaussian profiles. For the rectangular profiles, experimental estimates of thickness and density will only be accurate when the true thickness is greater than about 1.5 times (for the bone reconstruction kernel) or 2.0 times (for the standard kernel) the full width at half maximum of the point spread function (PSF) of the imaging system. For Gaussian profiles imaged by a system with a Gaussian PSF, there are straightforward analytical expressions for the overestimation of thickness and underestimation of density: and these are useful approximations to the simulations of Gaussian profiles with experimental (pseudo-Gaussian) PSFs. We have demonstrated that thresholding of the vertebral image cannot provide accurate estimates of cortical thickness and density because the appropriate threshold level requires foreknowledge of the cortical thickness. To circumvent such difficulties we suggest that the average value of the peak CT numbers measured along the medial axis of the cortical shell be adopted as an index of cortical shell strength, since its value depends on both the density and the thickness of the shell.

Computer Simulation↗
PubMed1999

Home-based management can achieve intensification cost-effectively in type I diabetes.

BACKGROUND: Newly diagnosed insulin-dependent diabetic children are most often admitted to hospital for education and insulin management and subsequently followed in outpatient clinics or office settings. However, most could be managed at home, given adequate family and health care team support and subsequent follow-up facilitated by home-based nursing intervention. We conducted a randomized trial of clinical, psychosocial, and cost effects of home-based management in a 2-year follow-up study of newly diagnosed diabetic children. METHODS: Sixty three patients were randomly assigned to traditional hospitalization and outpatient follow-up (hospital-based group) or home management (home-based group). Treatment differences between the two groups consisted of duration of initial hospital stay, site and timing of initial teaching, and nature and extent of subsequent nursing follow-up. Metabolic control was assessed by means of quarterly glycosylated hemoglobin measurements for 24 months and then at 36 months. Diabetes-related adverse events, knowledge of diabetes, adherence to the diabetes regimen, psychosocial impact, and social (total) costs incurred were assessed for 24 months. FINDINGS: Glycosylated hemoglobin concentrations were significantly lower in the home-based group at 12 to 24 months and at 36 months. Both groups had comparable numbers of diabetes-related adverse events. There were no significant group differences in psychosocial impact. Parents in the home-based group spent significantly fewer hours on diabetes care and incurred significantly lower out-of-pocket expenses during the 1st month. Health care sector costs were significantly higher. Hospital costs were $889 higher, and government costs $890 higher per child. Social (total) costs were only $48 higher per case (NS) with home care when parents' time was valued at $11.88 per hour. INTERPRETATION: Home-based management for newly diagnosed diabetic children can result in better metabolic control and similar psychosocial outcomes compared with traditional hospital- and clinic-based care without notable effects on social (total) costs.

Child↗
PubMed1999

Newly discovered anti-inflammatory properties of the benzamides and nicotinamides.

Our laboratory has concentrated on the possible regulation the benzamides and nicotinamides may have on the processes of DNA repair and apoptosis. Recent reports have suggested that both apoptosis and inflammation are regulated by the transcription factor NF-kappaB. We have initiated studies regarding the hypothesis that the benzamides and nicotinamides could inhibit the production of tumor necrosis factor alpha (TNFalpha) and the inflammatory response as well as induce apoptosis via inhibition of NF-kappaB. Our data have shown that nicotinamide and two N-substituted benzamides, metoclopramide (MCA) and 3-chloroprocainamide (3-CPA), gave dose dependent inhibition of lipopolysacharide induced TNFalpha in the mouse within the dose range of 10-500 mg/kg. Moreover, lung edema was prevented in the rat by 3 x 50 mg/kg doses of 3-CPA or MCA, and 100-200 microM doses of MCA could also inhibit NF-kappaB in Hela cells. Taken together these data strongly support the notion that benzamides and nicotinamides have potent anti-inflammatory and antitumor properties, because their primary mechanism of action is regulated by inhibition at the gene transcription level of NF-kappaB, which in turn inhibits TNFalpha and induces apoptosis.

Animals↗
PubMed1998

Induction of sensitivity to NK-mediated cytotoxicity by TNF-alpha treatment: possible role of ICAM-3 and CD44.

SR-91 is a natural killer (NK)-resistant leukemic cell line expressing a low level of ICAM-1. Pre-treatment of SR-91 cells with TNF-alpha or IFN-gamma, increased both ICAM-1 (CD54) expression on SR-91 cells and binding to the human NK cell line NK-92. However, only TNF-alpha-treated SR-91 cells became sensitive to killing by NK-92 cells. The increased binding induced by both cytokines and the TNF-alpha-induced sensitivity of SR-91 cells to NK-92 cell killing were abrogated by anti-LFA-1 mAb as well as by a combination of antibodies against the three ligands of LFA-1 (CD11a/CD18), ICAM-1 (CD54), ICAM-2 (CD102) and ICAM-3 (CD50). This indicated that LFA-1 interaction with the three ICAMs on SR-91 cells is essential for effector-target cell binding (which is a prerequisite for subsequent target cell lysis), but is insufficient to render the SR-91 cells sensitive to killing by NK-92 cells. TNF-alpha, but not IFN-gamma also induced the activation of LFA-1, CD44 and beta1 integrins on SR-91 cells. Based on these observations we propose that the differential effect of TNF-alpha and IFN-gamma could be related to the activation of certain adhesion molecules on the surface of SR-91 cells by TNF-alpha that, upon interaction with their counter-receptors on NK-92 cells, lead to the activation of the NK-92 cells.

Antigens, CD↗
PubMed1998

Limitations of clinical CT in assessing cortical thickness and density.

The peak CT number (CT) and full width at half maximum (FWHM) were obtained from the image profiles of aluminium of thickness ranging from 0.1-9.5 mm. The scans were performed at different fields of view (FOVs) and with different reconstruction algorithms ('bone' and 'standard'). Above 3 mm, CT and FWHM provide measures of the density and thickness which are largely independent of FOV (i.e. pixel size) and algorithm. Below 3 mm, CT falls progressively whilst FWHM remains relatively constant. At these small thicknesses the effect of FOV on CT is more pronounced when the bone algorithm is used, whilst FWHM remains relatively constant and independent of both FOV and algorithm. The results are discussed in terms of thickness relative to pixel size and spatial resolution as characterized by the point spread function. A linear relationship was found between the product CT x FWHM and thickness that is independent of both FOV and algorithm. This product may be useful in studies of cortical bone and changes due to osteoporosis.

Algorithms↗
PubMed1998

When should a child be in the hospital? A. Frederick North, Jr, MD, revisited.

OBJECTIVES: My objective was to revisit the issues and approaches raised in a seminal article published in Pediatrics in 1976 by A. Frederick North, Jr, entitled "When Should a Child Be in the Hospital?" Dr North proposed a set of nine criteria to guide the evaluation of appropriateness of admission to hospital. These were based on a core assertion that, "The need to hospitalize a child is dependent on the special services which the child requires rather than upon the diagnosis." This original work antedated more recent activities and publications in the area of appropriateness evaluation as applied to pediatrics (such as the Pediatric Appropriateness Evaluation Protocol), but is more context-specific than later works in the field. METHODS: A review of the literature concerning temporal trends in hospital use for children in North America was undertaken. This was done to place some of the subsequent observations in a macrocontext of overall trends in hospital use. A review of the English language literature focusing on alternatives to hospitalization and contextual evolution affecting patterns of hospital care for children is presented. Factors influencing each of the nine admission criteria proposed by North are reviewed and discussed in turn. RESULTS: Overall rates of hospitalization declined by 46% and 41% in the United States and Canada, respectively, during the 1971 to 1993 interval. The relative composition by diagnostic category in two specific pediatric hospital settings also evolved substantially during the 2 decades. Many of North's specific criteria required extensive revision or updating to match the contextual realities of the 1990s. CONCLUSIONS: Although important overall shifts have occurred in the absolute levels and relative composition of pediatric hospitalization, Dr North's core assertion, relating to the need for specific services driving the need for hospitalization, has largely stood the test of time.

Anesthesia, General↗
PubMed1997

Reliability and validity of proxy respondent information about childhood injury: an assessment of a Canadian surveillance system.

The reliability and validity of proxy respondent information in the Canadian Hospitals Injury Reporting and Prevention Program surveillance system was assessed. A standardized form was used to collect data on injury date, location, context (activity at the time), breakdown factor (what went wrong), mechanism, product involvement, safety precaution use, and motor vehicle involvement. The test-retest method determined reliability, with the kappa coefficient quantifying agreement between respondent information provided in the emergency department and later during a telephone interview. Of 421 eligible respondents, 325 (77%) completed the telephone interview, with a median time to interview of 33 hours (range 24-70 hours). Agreement was high for all items; kappa coefficients ranged from 0.79 (substantial agreement) to 1.00 (perfect agreement). Reliability was not significantly modified by respondent view of the injury event, age of the child, language of the form, or level of respondent education. Validity was determined by measuring the agreement between respondent information and that provided by an independent witness. Witness information was considered to represent the truth. Of the 140 injury events selected, 92 (66%) had the form completed by both the original respondent and an independent witness. Kappa coefficients were greater than 0.65 for all but one item (safety precaution use), and the positive predictive value of respondent information for item categories whose prevalence was > or = 0.25 ranged from 0.82 to 0.95. The authors conclude that proxy respondent data on childhood injury are both reliable and valid.

Adolescent↗
PubMed1997

The role of tumor-associated macrophages in the delivery of liposomal doxorubicin to solid murine fibrosarcoma tumors.

Murine fibrosarcoma tumors arising from subcutaneous inoculation of FSa-N cells exhibit 4-fold higher tumor-associated macrophage (TAM) levels than those from the FSa-R line. These solid tumors were used to assess the role of TAMs in the accumulation of liposomal anticancer drugs. Two liposomal formulations of doxorubicin were investigated: a conventional formulation composed of distearoylphosphatidylcholine (DSPC) and cholesterol and a sterically stabilized liposomal formulation composed of DSPC/cholesterol/poly (ethylene glycol)-modified distearoylphosphatidyethanolamine (PEG-PE). Circulating concentrations of PEG-PE containing liposomes 24 h after i.v. administration were 3-fold greater than those observed after administration of conventional liposomes. No differences were observed in drug retention or tumor (FSa-R or FSa-N) drug and liposomal lipid delivery when comparisons were made between different liposomal formulations. However, tumor doxorubicin concentrations were increased as much as 4-fold for liposomal formulations relative to free drug. Further, there was a 1.5- to 2-fold increase in doxorubicin delivery to TAM-enriched FSa-N tumors compared with FSa-R tumors. Fluorescence microscopy studies revealed a poor correlation between CD11b (Mac-1) positive cells (TAMs) and the appearance of doxorubicin fluorescence. These results suggest that uptake of liposomal drugs by TAMs does not account for the enhanced accumulation of liposomal drugs in solid tumors. Rather, the increased tumor drug delivery may be related to alternative TAM-mediated processes that increase tumor vascular permeability. Therapeutic studies demonstrated that increased tumor drug uptake observed for the liposomal doxorubicin formulations led to marginal improvements in antitumor activity, and it is suggested that much of the drug delivered in liposomal form is not biologically available.

Animals↗
PubMed1996

Quantitative CT in the measurement of bone quantity and bone quality for assessing osteoporosis.

The biomechanical strength of the skeleton, and hence the risk of future fractures, depends on both the bone quantity (assessed in terms of bone mineral density) and bone quality (assessed in terms of the integrity of its internal architecture). Precise methods of measuring the calcium-equivalent density of both the trabecular and cortical components of vertebral bone using quantitative computed tomography are presented. For a group of post-menopausal Kuwaiti females, we have shown that the trabecular and cortical components are highly correlated with each other at both the L3 and L4 lumbar vertebral levels, with correlation coefficients of 0.78 and 0.74 (P < 0.0001) respectively. We have explored the anisotropic distribution of trabecular bone and considered the use of the standard deviation and the coefficient of variation of trabecular CT numbers as texture indicators and surrogate measures of bone quality. The coefficient of variation was the better texture indicator: used with bone mineral density values it successfully discriminated between two classes of patients (those with fractures and those without) with high sensitivity (> or = 89%) and specificity (> or = 82%).

Aged↗
PubMed1994

Alternative splicing of CD44 pre-mRNA in human colorectal tumors.

Expression of the CD44 molecule has been linked to tumor growth and metastases in both human and rodent cancers. Alternatively spliced variants expressed in rat and mouse tumors have been shown to confer metastatic potential to non-metastatic carcinoma cell lines, and human homologues of rat variant mRNA sequences are expressed in human tumors. In the present study matched sets of RNA from adenocarcinomas of the colon and distant normal mucosa were assayed for CD44 expression by quantitative RT-PCR. Retrospective analysis revealed that colonic tumor cells had both quantitative and qualitative differences in CD44 expression when compared to normal mucosa. These were: 1) an increase in levels of CD44 transcripts, 2) an increase in levels of alternatively spliced transcripts, 3) the presence of larger alternatively spliced transcripts with inserts > 400 bases and 4) the primary alternatively spliced CD44 isoform in colonic adenocarcinomas in all cases is CD44R. Interestingly, two patterns of CD44 isoform expression termed "variant dominant" or "balanced" patterns of expression, based on the ratio of variant to standard CD44 transcripts (R+V's/H), could be differentiated. An unfavorable prognosis was suggested for tumors expressing increased levels of CD44 variant exons previously associated with tumor metastasis. Specifically, patients with tumors expressing the "variant dominant" pattern of expression irregardless of Dukes classification and Dukes C and D staged tumors of both patterns exhibited a poorer prognosis.

Adenocarcinoma↗
PubMed1994

Spectral analysis of laser Doppler signals in real time using digital processing.

A versatile spectrum analyser was developed to generate and display laser Doppler shift signals, and derived parameters, continuously in real time using a digital signal processing chip. A major attraction of the system is that it is entirely programmable, so that both the algorithms and the attributes of the system, such as window function and frame overlap, can be easily altered. It was used to investigate the relative merits of a variety of algorithms using a blood-flow phantom. An index based on the first moment of the Doppler power spectrum was found to be the most reliable flow indicator, with linearity extending towards a velocity of 5 mm s-1 for a blood haematocrit of 5%. The system is not limited to analysis based on the fast Fourier transform (FFT), and is suitable for non-linear techniques such as maximum entropy spectral estimation (MESE).

Algorithms↗