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Biomedical subjects

J A Little

Publications and source records attributed to J A Little.

At least 19 recordsLinked to original sources
PubMed2002

Deforming a preoperative volume to represent the intraoperative scene.

Soft-tissue deformation can be a problem if a preoperative modality is used to help guide a surgical or interventional procedure. We present a method that can warp a preoperative CT image to represent the intraoperative scene shown by an interventional fluoroscopy image. The method is a novel combination of a 2D-3D image registration algorithm and a deformation algorithm that allows rigid bodies to be incorporated into a nonlinear deformation based on radial basis functions. The 2D-3D registration algorithm is used to obtain information on relative vertebral movements between preoperative and intraoperative images. The deformation algorithm uses this information to warp the preoperative image to represent the intraoperative scene more accurately. Images from an aortic stenting procedure were used. The observed deformation in our experiment was 5 degrees flexion and 5 mm lengthening of the lumbar spine over a distance of four vertebrae. The vertebral positions in the warped CT volume represent the intraoperative scene more accurately than in the preoperative CT volume. Although we had no gold standard with which to assess the registration accuracy of soft-tissue structures, the position of such structures within the warped CT volume appeared visually realistic.

Algorithms↗
PubMed2001

Practical approach to determining costs and frequency of adverse drug events in a health care network.

The frequency, preventability, severity, root causes, and projected costs of adverse drug events (ADEs) occurring after or causing admission to a four-hospital integrated academic health network were studied. The sample included all admissions during a 53-day study period. Events were identified through daily record review of a random patient sample, computerized flags, and self-reporting. A case review committee validated the occurrence, classification, and root causes of the events. Additional length of stay and costs associated with ADEs were analyzed by using a case-control, multiple linear regression model. The estimated ADE rate during hospitalization was 4.2 events per 100 admissions, with a cost of $2162 per ADE. In addition, 3.2% of admissions were caused by ADEs, with an associated cost of $6685 per event. Fifteen percent of hospital ADEs and 76% of ADEs causing admission were judged preventable. The annual cost to the organization for events occurring during hospitalization was $1.7 million, and the cost of preventable ADEs was $260,000, while the projected costs of preventable ADEs causing admission were $3.8 million. The rate of admissions to the mental health center caused by ADEs was higher than for other settings at 13.6%, with a cost of preventable ADEs of $1.3 million. Patient noncompliance was judged to be the cause of the 69% of the ADEs causing admission. Seventy-one percent of the serious medication errors occurred at the prescribing stage of the medication-use process. ADEs were frequent, costly, and often preventable and resulted in many admissions to a mental health center.

Costs and Cost Analysis↗
PubMed2000

Bleeding risk and platelet transfusion refractoriness in patients with acute myelogenous leukemia who undergo autologous stem cell transplantation.

Therapy for acute myelogenous leukemia can be complicated by alloimmunization to histocompatibility antigens (HLA), with resultant refractoriness to platelet transfusions. Autologous peripheral blood or bone marrow stem cell transplantation (referred here collectively as 'autoBMT') is emerging as a standard consolidative strategy in acute myelogenous leukemia (AML). We had noted life-threatening bleeding associated with platelet transfusion refractoriness following autoBMT; we therefore retrospectively analyzed 39 AML patients for this complication following BMT. All patients received high-dose chemoradiotherapy, followed by infusion of allogeneic sibling donor (n = 12, alloBMT) or autologous (n = 27, autoBMT) stem cells. HLA alloimmunization was assessed if patients were suspected of immune refractoriness to random donor platelet transfusions. Within 100 days of stem cell infusion, one of three alloBMT and six of 12 autoBMT recipients tested were HLA alloimmunized (not statistically significant, NS). Five of six HLA alloimmunized autoBMT patients experienced delayed bleeding, which contributed to their demise while still in remission (P < 0.001). Increased platelet requirements in HLA alloimmunized autoBMT recipients were observed between days 61 and 100 post-BMT, at a median of 211 platelet transfusions vs 0 in non-alloimmunized autoBMT patients (P < 0.01) and 17 in alloBMT patients. Our data suggest that platelet transfusion refractoriness, when associated with HLA alloimmunization, is a risk factor for increased platelet transfusion requirements, delayed bleeding, and poor outcome following autoBMT for AML.

Adolescent↗
PubMed1999

The effect of growth hormone secretagogues and neuropeptide Y on hypothalamic hormone release from acute rat hypothalamic explants.

Growth hormone (GH) secretagogues (GH-releasing peptides and their non-peptide analogues) stimulate growth hormone release via specific G-protein coupled receptors both directly from the pituitary gland and through stimulation of the hypothalamus. The exact mechanism of action in the hypothalamus is not known. The presence of endogenous GH releasing hormone (GHRH) seems to be necessary for the in-vivo actions of growth hormone secretagogues (GHSs), but data suggest that further factors must be involved as well. The effect of GHSs is not entirely specific for the GH axis; they release prolactin and stimulate the hypothalamo-pituitary-adrenal axis causing elevations in circulating ACTH and cortisol levels in both animal and human studies. Recently, it has also been suggested that GHSs stimulate hypothalamic neuropeptide Y (NPY) neurones. In the present study, we have therefore investigated the direct effect of several GHSs (GHRP-6, hexarelin and the non-peptide analogues L-692, 429 and L-692, 585) on GHRH, somatostatin (SS), corticotrophin-releasing hormone (CRH) and arginine vasopressin (AVP) release in vitro in an acute rat hypothalamic incubation system. We also assessed the effect of NPY on GHRH, SS and AVP release. Freshly removed hypothalami were incubated in control media for 20 min and then in 1-4 consecutive 20-min periods in each of the test substances at different concentrations. There was no significant change in either the basal or potassium-stimulated release of GHRH or SS at low concentrations of any of the secretagogues; however, at millimolar doses a paradoxical inhibition of GHRH was observed with GHRP-6, hexarelin and L-692 585 (data are expressed as the ratio of treated to preceding basal release; at 20 min control group: 0.97+/-0.02, GHRP-6: 0.55+/-0.04, P<0.001 compared to control group; hexarelin: 0. 56+/-0.06, P<0.001, L-692,585: 0.70+/-0.03, P<0.001), while SS was stimulated after 60 or 80 min (at 80 min control: 0.80+/-0.03, hexarelin: 1.23+/-0.07, P<0.05 and L-692,585: 1.37+/-0.11, P<0.05). GHSs stimulated hypothalamic AVP release (at 20 min control: 0. 99+/-0.06 ratio to basal release, 10-4 M concentration of GHRP-6: 6. 31+/-1, P<0.001, hexarelin: 1.88+/-0.4, P<0.01, L-692,429: 1.90+/-0. 5, P<0.05 and L-692,585: 2.34+/-0.96, P<0.01), while no stimulatory effect was found on CRH release. NPY significantly stimulated SS and inhibited basal and potassium-stimulated GHRH release, while potentiating potassium-evoked AVP secretion. The Y1 receptor antagonist BIBP 3226 did not inhibit the effects of NPY on SS, GHRH or AVP release. We therefore conclude that, in this in-vitro rat hypothalamic incubation model, growth hormone secretagogues stimulate the release of AVP but have no effect on either GHRH, SS or CRH at low doses; at high doses paradoxically they inhibit the hypothalamic GH axis similar to in-vivo data in the rat. We speculate that these effects might be mediated by NPY.

Animals↗
PubMed1999

The prevalence of hyperlipidemia in women and its association with use of oral contraceptives, sex hormone replacement therapy and nonlipid coronary artery disease risk factors. Canadian Heart Health Surveys Research Group.

OBJECTIVE: To report the prevalence of lipid and nonlipid coronary artery disease risk factors in women classified by use of oral contraceptives or sex hormone replacement therapy. DESIGN, SETTING AND PARTICIPANTS: A population-based cross-sectional survey in nine Canadian provinces (not including Nova Scotia) between 1988 and 1992 invited 13,506 women aged 18 to 74 years to participate. During a clinic visit after a home interview, a blood sample was obtained following a fast of 8 h or more from 8637 women. OUTCOME MEASURES: Fasting plasma total cholesterol, triglycerides, low density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol, blood pressure, smoking status, self-reported diabetes, and self-reported use of oral contraceptive or sex hormone replacement therapy pills. MAIN RESULTS: The prevalence of oral contraceptive use was 41% for women 18 to 24 years old and 20% for women 25 to 34 years old. The prevalence of sex hormone replacement therapy was 4% for women 35 to 44 years old, 20% for women 45 to 64 years old and 11% for women 65 to 74 years old. Users of sex hormone replacement therapy aged 35 to 44 years had slightly higher mean LDL cholesterol than nonusers (3.04 versus 2.89 mmol/L). Users and nonusers aged 45 to 54 years had similar LDL cholesterol levels, and users aged 55 to 64 and 65 to 74 years had lower LDL cholesterol and higher HDL cholesterol levels, respectively, than nonusers. Triglyceride levels were higher in oral contraceptive users and in younger women on sex hormone replacement therapy than in nonusers. In the general population of Canada the use of oral contraceptives in women less than age 35 years had only a marginal effect on the prevalence of lipid and nonlipid risk factors. Women aged 18 to 24 years using oral contraceptives had a higher mean LDL cholesterol level of 2.73 versus 2.35 mmol/L for nonusers. The prevalence of lipid and nonlipid risk factors in women using sex hormone replacement therapy increased slightly for those aged 35 to 54 years and decreased in women aged 55 to 74 years. A lower percentage of women using sex hormone replacement therapy, aged 55 to 74 years, had high risk LDL cholesterol levels (21% versus 36% for nonusers). A larger percentage of women using sex hormone replacement therapy had low risk HDL cholesterol levels (54% versus 29% for nonusers). The nonlipid risk factor profile for women aged 35 to 54 years on sex hormone replacement therapy was less favourable than for nonusers: obesity was more common (36% versus 28%, respectively), hypertension was higher (22% versus 12%, respectively), and the proportion of women with one or more nonlipid risk factors was higher. The nonlipid risk factor profile for women 55 to 74 years of age who were using sex hormone replacement therapy was more favourable than for nonusers: obesity was lower (31% versus 47%, respectively), smoking was lower (7% versus 16%, respectively), sedentary behaviour was lower (28% versus 37%, respectively), and fewer women had two or more of these risk factors (31% versus 52%, respectively). CONCLUSION: The findings suggest that women at higher risk for coronary artery disease tend to have a lower prevalence of use of sex hormone replacement therapy.

Adolescent↗
PubMed1999

Prevalence of high plasma triglyceride combined with low HDL-C levels and its association with smoking, hypertension, obesity, diabetes, sedentariness and LDL-C levels in the Canadian population. Canadian Heart Health Surveys Research Group.

OBJECTIVE: To report the associations of plasma triglyceride, high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C) with nonlipid coronary artery disease risk factors. In particular, the associations for persons with high triglyceride and low HDL-C levels were examined. DESIGN: A stratified random probability sample of 29,855 men and women aged 18 to 74 years from the Canadian Heart Health Surveys (1986 to 1992) in 10 provinces. Blood samples were obtained from 18,555 participants who had fasted for 8 h or more. Plasma lipids were determined at the J Alick Little Lipid Research Laboratory, Toronto, Ontario, with standardization of the Centers for Disease Control Lipid Standardization Program, Atlanta. OUTCOME MEASURES: Fasting plasma total cholesterol, triglyceride, LDL-C and HDL-C levels. MAIN RESULTS: The prevalence of men with triglyceride levels above 1.7 mmol/L and HDL-C levels below 0.9 mmol/L was 10%, compared with 3% for men with triglyceride levels below 1.7 mmol/L and HDL-C levels below 0.9 mmol/L. The prevalence of women with triglyceride levels above 1.7 mmol/L and HDL-C levels below 0.9 mmol/L was 3% compared with a prevalence of less than 1% for women with triglyceride levels below 1.7 mmol/L and HDL-C levels below 0.9 mmol/L. Even when plasma LDL-C was low at less than 3.4 mmol/L, there was an age trend for increasing prevalences of the combination of triglyceride levels 2.3 mmol/L or greater and HDL-C levels less than 0.9 mmol/L in both sexes. The prevalence of a triglyceride levels 2.3 mmol/L or greater combined with an HDL-C level below 0.9 mmol/L was increased in groups who were cigarette smokers, diabetic, hypertensive, obese or sedentary, or who had higher LDL-C levels in both sexes, and the increase was even greater in the presence of two or more of these other risk factors. CONCLUSIONS: Among men or women with low HDL-C and high triglyceride levels, smoking, diabetes, sedentariness, hypertension and obesity were much more prevalent than among those at low risk with high HDL-C and low triglyceride levels.

Adolescent↗
PubMed1999

Plasma lipids and lipoprotein reference values, and the prevalence of dyslipoproteinemia in Canadian adults. Canadian Heart Health Surveys Research Group.

OBJECTIVE: To report reference values for plasma lipids and lipoproteins in Canadian adults and the prevalence in the population of various levels of risk for coronary artery disease from dyslipoproteinemia. DESIGN, SETTING AND PARTICIPANTS: Population- based provincial heart health cross-sectional surveys in 10 provinces between 1986 and 1992 invited 29,855 men and women aged 18 to 74 years to participate. During a clinic visit after a home interview a blood sample was obtained following a fast of 8 h or more from 18,555 people. Plasma lipid levels were determined at the J Alick Little Lipid Research Laboratory, Toronto, with standardization of the Centers for Disease Control Lipid Standardization Program, Atlanta. OUTCOME MEASURES: Fasting plasma total cholesterol, triglyceride, low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) and non-HDL-C levels. MAIN RESULTS: Mean plasma total cholesterol, LDL-C, non-HDL-C and triglyceride levels increased with age in men to a peak at around age 54 years, while in women the increases were more gradual at a lower level until age 54 years, after which they increased appreciably eventually exceeding values for men. A high percentage of adults were at increased risk for coronary artery disease: 44% had elevated total cholesterol levels above 5.2 mmol/L; 14% had LDL-C levels above 4.1 mmol/L; 8% had HDL-C values below 0.9 mmol/L; and 14% had triglyceride levels above 2.3 mmol/L. Eleven per cent of adults had both total cholesterol level above 6.2 mmol/L and LDL-C level above 4.1 mmol/L. CONCLUSION: The high prevalence of Canadian adults at risk because of elevated plasma lipid levels strongly indicates the need for comprehensive public health programs to reduce plasma lipid levels in the population and the need to encourage physicians to treat those at high risk.

Adult↗
PubMed1999

Impact of different blood lipid evaluation and treatment guidelines on the proportion of Canadians identified and treated for elevated blood cholesterol. Canadian Heart Health Surveys Research Group.

OBJECTIVE: To report on the impact of different blood lipid evaluation and treatment guidelines on the proportion of Canadians identified and treated for high blood cholesterol. DESIGN, SETTING AND PARTICIPANTS: The Canadian Heart Health Surveys were carried out in Canada between 1986 and 1991. The data used in this study were from cross-sectional probability samples of adults aged 18 to 74 years, gathered in four provincial health surveys (Quebec, Alberta, Manitoba and Ontario) between 1989 and 1992, which obtained information on family history of heart disease. Data reported are for 7238 subjects fasting 8 h or more and providing a blood sample. All blood lipid analysis were done at the J Alick Little Lipid Research Laboratory, University of Toronto, which is standardized according to the National Heart, Lung, and Blood Institute, Centers for Disease Control (Atlanta) Lipid Standardization Program. OUTCOME MEASURES: With respect to the four guidelines examined--the Canadian Consensus Conference on Cholesterol (CCCC), 1987; the Toronto Working Group on Cholesterol Policy (TWG), 1990; the Canadian Task Force on the Periodic Health Examination (PHE), 1993; and the National Cholesterol Education Program (NCEP), 1993, in the United States--a comparison of the proportion of individuals in the population for whom a lipid profile was constructed, and who were prescribed a diet and drug therapy under different assumptions of success with dietary therapy for each guideline. MAIN RESULTS: Major differences were observed in the impact of the various guidelines with respect to the percentage of subjects who were tested, provided with a lipid profile, and eligible for diet and/or drug therapy. In general the percentages in each group were higher for the CCCC and the NCEP guidelines than for the PHE and TWG guidelines. CONCLUSION: The divergent results obtained from the application of the various guidelines are cause for concern and explain in part the confusion that surrounds the topic of blood cholesterol in public health and clinical contexts. Public health policy in the area of cardiovascular disease prevention would benefit from explicit consideration of various types of criteria for formulation of identification and treatment guidelines.

Adolescent↗
PubMed1998

Silencing and activation of embryonic globin gene expression.

An understanding of the mechanisms that control developmental stage-specific transcription of globin genes offers the promise of successful therapeutic activation of fetal or embryonic beta-type genes in beta-thalassemia syndromes. A large body of evidence supports the notion of conservation of such mechanisms across vertebrate species and validates the use of pre-clinical studies of silencing and activation of fetal or embryonic globin genes in animals. Using globin gene transfections into primary avian erythroid cells and cultured murine erythroleukemia cells, we have studied mechanisms involved in stage-specific embryonic beta-type globin gene silencing and activation. These studies show that 1) methylation of the exact CpG nucleotides that are methylated in normal adult erythroid cells in vivo is capable of blocking transcription of a transfected embryonic globin gene promoter via binding of a methyl DNA binding protein in primary erythroid cells. 2) Activation of embryonic beta-type globin gene transcription in adult erythroid cells by short chain fatty acids is mediated through specific DNA sequences both in the promoter and downstream of the promoter.

Animals↗
PubMed1998

A three-component deformation model for image-guided surgery.

In image-guided surgery it is necessary to align preoperative image data with the patient. The rigid-body approximation is usually applied, but is often not valid due to tissue deformation. Non-rigid deformation algorithms have been applied to related, but not identical problems, such as atlas matching and surgery simulation. In image-guided surgery we have the additional information that the deformation is constrained by the physical properties of the different tissues. The most important properties that must be incorporated are the rigidity of bone, the unconstrained nature of fluid regions and the relatively smooth deformation of soft tissue. Hence, we have developed a simplified model of tissue deformation based on a three-component system. Rigid regions are constrained by the rigid-body transformation and fluid regions are unconstrained. A number of energy models for deformable tissues have been compared. The model can be deformed using intraoperative data, in this case landmarks, using a technique similar to active contours. A novel strategy to avoid folding in the transformation is described. Our method was applied to MRI and CT data from a neurosurgery patient with epilepsy. Although the current implementation is only two dimensional, the initial results are promising. As the algorithm must ultimately run in or near 'real-time' an improved implementation of the energy minimization is underway. This paper presents the problem of tissue deformation, which has received little attention in the literature and outlines the framework we have developed for tackling this difficult subject.

Algorithms↗
PubMed1998

A comparison of similarity measures for use in 2-D-3-D medical image registration.

A comparison of six similarity measures for use in intensity-based two-dimensional-three-dimensional (2-D-3-D) image registration is presented. The accuracy of the similarity measures are compared to a "gold-standard" registration which has been accurately calculated using fiducial markers. The similarity measures are used to register a computed tomography (CT) scan of a spine phantom to a fluoroscopy image of the phantom. The registration is carried out within a region-of-interest in the fluoroscopy image which is user defined to contain a single vertebra. Many of the problems involved in this type of registration are caused by features which were not modeled by a phantom image alone. More realistic "gold-standard" data sets were simulated using the phantom image with clinical image features overlaid. Results show that the introduction of soft-tissue structures and interventional instruments into the phantom image can have a large effect on the performance of some similarity measures previously applied to 2-D-3-D image registration. Two measures were able to register accurately and robustly even when soft-tissue structures and interventional instruments were present as differences between the images. These measures were pattern intensity and gradient difference. Their registration accuracy, for all the rigid-body parameters except for the source to film translation, was within a root-mean-square (rms) error of 0.54 mm or degrees to the "gold-standard" values. No failures occurred while registering using these measures.

Algorithms↗
PubMed1998

Elevated LDL triglyceride concentrations in subjects heterozygous for the hepatic lipase S267F variant.

Although naturally occurring loss-of-function mutations in human hepatic lipase (HL) have been described, the biochemical phenotype of heterozygous HL deficiency remains ill defined. This may be due to the relatively small numbers of heterozygous adult carriers of HL mutations in index kindreds. We have identified several new heterozygotes for the catalytically inactive, nonsecreted HL variant S267F in the kindred that was originally ascertained because of hypertriglyceridemia due to the mutant, secreted, circulating apolipoprotein (apo) CII variant apo CII-T. Pairwise comparisons with family controls showed that only the plasma low density lipoprotein triglycerides (LDL TGs) were higher in 11 simple heterozygotes for HL S267F (P=0.002). In contrast, both plasma total TGs and LDL TGs were significantly higher in 12 simple heterozygotes for apo CII-T than in family-matched control subjects (P=0.005 and 0.009, respectively). These findings suggest that the TG content of LDL is increased by heterozygosity for 2 different mutations that affect different proteins involved in lipolysis. However, the mechanisms underlying this compositional change in LDL appear to be different for the 2 mutations, because the total TGs are also elevated in subjects heterozygous for apo CII-T but not in subjects heterozygous for HL S267F.

Adult↗
PubMed1998

Heterosis losses resulting from incorrect matings in a three-breed rotational crossbreeding system in pigs.

Losses in individual heterosis were estimated using performance records from 11,700 pigs, 959 litters, and 377 pens of pigs from a three-breed rotational crossbreeding system. Three types of rotational crossbred sows were produced using the Duroc, Landrace, and Yorkshire breeds. Twenty-nine Duroc, 27 Landrace, and 25 Yorkshire boars were mated to 275 sows to produce pigs with theoretical levels of breed heterozygosity of 85.7, 71.4, or 42.9% depending on the genetic composition of the sows and boars. Orthogonal polynomials for unequally spaced levels were used to partition sum of squares for individual heterozygosity into linear and quadratic responses. There was a linear decline in 56-d litter weight (-.222 kg; P < .01) for each 1% decrease in heterozygosity. Responses for pig weight at 56 d (-.02 kg; P < .001) and age at 105 kg (.12 d; P < .001) were linear for each 1% decrease in heterozygosity. Likewise, post-weaning average daily gain ( -.0004 kg/d; P < .05) and feed conversion (-.0001; P < .01) responses were linear for each 1% decrease in heterozygosity. There were linear responses for survival rates of pigs born alive to 21 d (-.089%; P < .01), alive from 21 to 56 d (-.025%; P < .05), alive from 56 d and to 105 kg (-.042%; P < .05), and from birth to 105 kg (excluding stillborn pigs) (-.129%; P < .001) for every 1% decline in heterozygosity from 85.7 to 42.9%, respectively. Quadratic responses were not important for any of the traits examined (P > .05). Decreased productivity, resulting from decreased heterozygosity, can be expected when three-breed rotational crossbred sows are mated to boars from the wrong breed.

Animals↗
PubMed1997

Methylation of the minimal promoter of an embryonic globin gene silences transcription in primary erythroid cells.

Methylation of cytosines in the dinucleotide CpG has been shown to suppress transcription of a number of tissue-specific genes, yet the precise mechanism is not fully understood. The vertebrate globin genes were among the first examples in which an inverse correlation was shown between CpG methylation and transcription. We studied the methylation pattern of the 235-bp rho-globin gene promoter in genomic DNA from primary chicken erythroid cells using the sodium bisulfite conversion technique and found all CpGs in the promoter to be methylated in erythroid cells from adult chickens in which the rho-globin gene is silent but unmethylated in 5-day (primitive) embryonic red cells in which the gene is transcribed. To elucidate further the mechanism of methylation-induced silencing, an expression construct consisting of 235 bp of 5' promoter sequence of the rho-globin gene along with a strong 5' erythroid enhancer driving a chloramphenicol acetyltransferase reporter gene, rho-CAT, was transfected into primary avian erythroid cells derived from 5-day embryos. Methylation of just the 235-bp rho-globin gene promoter fragment at every CpG resulted in a 20- to 30-fold inhibition of transcription, and this effect was not overridden by the presence of potent erythroid-specific enhancers. The ability of the 235-bp rho-globin gene promoter to bind to a DNA Methyl Cytosine binding Protein Complex (MeCPC) was tested in electrophoretic mobility shift assays utilizing primary avian erythroid cell nuclear extract. The results were that fully methylated but not unmethylated 235-bp rho-globin gene promoter fragment could compete efficiently for MeCPC binding. These results are a direct demonstration that site-specific methylation of a globin gene promoter at the exact CpGs that are methylated in vivo can silence transcription in homologous primary erythroid cells. Further, these data implicate binding of MeCPC to the promoter in the mechanism of silencing.

Animals↗