Biomedical subjects

G W Taylor

Publications and source records attributed to G W Taylor.

At least 37 records · Page 2Linked to original sources

PubMed2000

Pharmacokinetics and disposition of the novel dopamine agonist Z-7760 in rat after intravenous and oral administration.

1. Z-7760 (S(-)-N-[N-2-phenylethyl)-6-hexylamino]-N-propyl-5,6-dihydroxy-1,2,3,4-tetrahydro-2-naphthylamine dihydrobromide) is a potent dopamine D-1 and D-2 agonist synthesized during a search for agents to treat heart failure. Reported is the fate of the drug in rat. 2. 3H-Z-7760 was administered p.o. and i.v. to male Sprague-Dawley rats (0.4 mg and 400 microCi/kg in 0.1% ascorbic acid) and venous blood samples collected at intervals up to 48 h. Comparison of the AUC for total 3H showed that 37% of an oral dose of Z-7760 was absorbed. The percentage plasma 3H present as the parent compound fell from 82% 30 min after i.v. dosing to 12% after 24 h. After oral dosing, the fraction of plasma 3H present as unchanged Z-7760 was < 5% and this was essentially unaltered throughout the study. The long terminal elimination phase evident from 6 h was notable after both routes of administration. 3. The bile duct-cannulated rat was given 3H-Z-7760 p.o. (0.4 mg and 40 microCi/kg) and bile was collected for up to 22 h. Biliary excretion accounted for 30% of the dose. No parent compound was detected in the bile. 4. In further studies, other rats were dosed p.o. or i.v. with 3H-Z-7760 (0.4 mg and 400 microCi/kg) and urine and faeces were collected daily for 3 days. The major route of excretion was the faeces with 94-97% 3H recovered after oral and 70-73% after i.v. dosing. A further 4-7% was recovered in the urine after oral and 12-13% after i.v. dosing. 5. After oral administration of Z-7760 (100 mg/kg, 40 microCi/kg) to rats, the major metabolites in the urine were identified as the 5-O-methyl and glucuronic acid conjugates of Z-7760 by LC and MS. The glucuronide was only seen in urine after oral administration but 5-O-methyl-Z-7760 was present in urine and faeces after both routes of administration. 6. The low bioavailability of Z-7760 is the consequence of its poor absorption from the gastrointestinal tract as well as extensive first-pass metabolism that further reduces systemic blood concentrations after oral administration.

2-Naphthylamine↗

PubMed2000

Impact of oral diseases on systemic health in the elderly: diabetes mellitus and aspiration pneumonia.

Evidence is increasing that oral health has important impacts on systemic health. This paper presents data from the third National Health and Nutrition Examination Survey (NHANES III) describing the prevalence of dental caries and periodontal diseases in the older adult population. It then evaluates published reports and presents data from clinical and epidemiologic studies on relationships among oral health status, chronic oral infections (of which caries and periodontitis predominate), and certain systemic diseases, specifically focusing on type 2 diabetes and aspiration pneumonia. Both of these diseases increase in occurrence and impact in older age groups. The NHANES III data demonstrate that dental caries and periodontal diseases occur with substantial frequency and represent a burden of unmet treatment need in older adults. Our review found clinical and epidemiologic evidence to support considering periodontal infection a risk factor for poor glycemic control in type 2 diabetes; however, there is limited representation of older adults in reports of this relationship. For aspiration pneumonia, several lines of evidence support oral health status as an important etiologic factor. Additional clinical studies designed specifically to evaluate the effects of treating periodontal infection on glycemic control and improving oral health status in reducing the risk of aspiration pneumonia are warranted. Although further establishing causal relationships among a set of increasingly more frequently demonstrated associations is indicated, there is evidence to support recommending oral care regimens in protocols for managing type 2 diabetes and preventing aspiration pneumonia.

Adolescent↗

PubMed1999

Inhibition of prostaglandin E2 synthesis in abdominal aortic aneurysms: implications for smooth muscle cell viability, inflammatory processes, and the expansion of abdominal aortic aneurysms.

BACKGROUND: There is no treatment proven to limit the growth of abdominal aortic aneurysms, in which the histological hallmarks include inflammation and medial atrophy, with apoptosis of smooth muscle cells and destruction of elastin. METHODS AND RESULTS: Aneurysm biopsies were used for explant cultures, the preparation of smooth muscle cell cultures, and isolation of macrophages. Tissue macrophages stained strongly for cyclooxygenase 2. Prostaglandin E2 (PGE2) concentrations in aneurysm tissue homogenates, conditioned medium from explants, and isolated macrophages were 49+/-22 ng/g, 319+/-38 ng/mL, and 22+/-21 ng/mL, respectively. PGE2 inhibited DNA synthesis and proliferation in normal aortic smooth muscle cells (IC50, 23.2+/-3.8 and 23.6+/-4.5 ng/mL, respectively). In smooth muscle cells derived from aneurysmal aorta, PGE2 also caused cell death, with generation of oligonucleosomes. Conditioned medium from the mixed smooth muscle and monocyte cultures derived from explants also had potent growth-inhibitory effects, and fractionation of this medium showed that the growth-inhibitory molecule(s) coeluted with PGE2. In explants, indomethacin 10 micromol/L or mefenamic acid 10 micromol/L abolished PGE2 secretion and significantly reduced IL-1beta and IL-6 secretion. In a separate case-control study, the expansion of abdominal aortic aneurysms was compared in 15 patients taking nonsteroidal anti-inflammatory drugs and 63 control subjects; median growth rates were 1.5 and 3.2 mm/y, respectively, P=0.001. CONCLUSIONS: The adverse effects of PGE2 on aortic smooth muscle cell viability and cytokine secretion in vitro and the apparent effect of anti-inflammatory drugs to lower aneurysm growth rates suggest that selective inhibition of PGE2 synthesis could be an effective treatment to curtail aneurysm expansion.

Adolescent↗

PubMed1999

Eicosanoid biosynthesis in an advanced deuterostomate invertebrate, the sea squirt (Ciona intestinalis).

The eicosanoid generating potential of tunic, branchial basket, intestine, ovary and tadpole larvae from the sea squirt, Ciona intestinalis, was examined using a combination of reverse phase high performance liquid chromatography, gas chromatography-mass spectrometry and enzyme immunoassay. All organs examined synthesized the lipoxygenase products 12-hydroxyeicosapentaenoic acid (12-HEPE) and 8-HEPE implying that both 8- and 12-lipoxygenase activity are widely distributed in this species. In addition, tunic and branchial basket generated significant amounts of 8,15-diHEPE and smaller amounts of 8,15-dihydroxyeicosatetraenoic acid (8,15-diHETE), while tunic alone generated small amounts of conjugated tetraene-containing material with a UV chromophore and mass ion characteristic of a lipoxin-like compound. The broad range lipoxygenase inhibitors, esculetin and nordihydroguaiaretic acid, both caused a significant dose dependent inhibition of 12-HEPE and 8,15-diHEPE biosynthesis in tunic, while the specific 5-lipoxygenase inhibitor, REV-5901, and the specific 5-lipoxygenase activating protein inhibitor, MK-866, had no observable effect on the lipoxygenase profile of this tissue. Tunic, branchial basket, intestine and ovary all generated significant amounts of prostaglandin (PG) E and PGF immunoreactive material and smaller amounts of thromboxane B immunoreactive material as measured by enzyme immunoassay. The non-specific cyclooxygenase (COX) inhibitor, indomethacin, the selective COX-1 inhibitors, resveratrol and valerylsalicylate, and the specific COX-2 inhibitors, NS-398, etolodac and DFU (5,5-dimethyl-3-(3-fluorophenyl)-4-(4-methylsulphonyl) phenyl-2(5H)-furanone) all caused a significant dose dependent inhibition of the biosynthesis of PGE immunoreactive material. However, the specific COX-2 inhibitors were most effective, perhaps implying that a COX-2-like enzyme may be present in this species.

Animals↗

PubMed1999

The eicosanoid generating capacity of isolated cell populations from the gills of the rainbow trout, Oncorhynchus mykiss.

Rainbow trout gill filaments generated a wide range of eicosanoid products following calcium ionophore challenge. The putative lipoxygenase products were separated by reverse phase high performance liquid chromatography (RP-HPLC), while prostanoids were quantified by enzyme immunoassay. Three main monohydroxy compounds containing conjugated dienes were observed after RP-HPLC namely 12-(S) hydroxyeicosatetraenoic acid (12-HETE), 12-(S) hydroxyeicosapentaenoic acid (12-HEPE) and 14-(S) hydroxydocosahexaenoic acid (14-HDHE), derived from endogenous arachidonic, eicosapentaenoic and docosahexaenoic acids, respectively. Their identification was confirmed by mass spectrometry. A further five compounds containing conjugated trienes were also observed but in lesser amounts. One of these products was identified as 8,15-dihydroxyeicosatetraenoic acid (8,15-DiHETE) based on its UV spectrum, co-elution with authentic standard on RP-HPLC and mass spectrometry. Overall, the generation of these products suggests the presence of 12- and possibly 15-lipoxygenase activities in trout gill acting on endogenous sources of fatty acid. To determine if the various cell types in trout gill had differing eicosanoid generating potential, gills were disrupted and the resultant cell suspensions separated by density gradient centrifugation. Following this three bands were formed on the gradients and the cell populations from these were characterised using periodic acid Schiff's (PAS) reactivity for mucosubstances, haematoxylin and eosin staining, and immunoreactivity with both monoclonal and polyclonal antibodies. The first band consisted of polygonal cells and other more minor cell types, the second cell band contained mainly polygonal and PAS-positive goblet epithelial cells, while the third band consisted of mainly erythrocytes. There were significant differences in the eicosanoid generating potential of the isolated cells, with cells from the second band generating significantly more 12-HETE and 8,15-DiHETE than those from both the first band and unfractionated populations. The eicosanoid generating activity of the trout gill epithelial cell line, RTG-W1, was also elucidated. It proved to be a modest generator of eicosanoids in that only low levels of thromboxane B2 and prostaglandin E2 were detected while no lipoxygenase products were observed.

Animals↗

PubMed1999

Periodontal treatment and its effects on glycemic control: a review of the evidence.

Persisting poor glycemic control has been shown to be associated with the incidence and progression of diabetes-related complications. The bulk of oral health-related research has focused on the impact of diabetes on periodontal health, yet there are several lines of evidence to support the plausibility of the notion that periodontal infections contribute to problems with glycemic control. This article reviews the body of English-language literature containing reports of clinical research that has considered the relationship between treatment of periodontal diseases and improvement in glycemic control in humans. Although there is supportive clinical and epidemiologic evidence, equivocal and contrary evidence also exists. It is concluded from this review that the quantity, breadth, and strength of evidence-based knowledge are currently insufficient to establish periodontal therapy as influential in improving glycemic control in either type 1 or type 2 diabetes. Further rigorous, systematic study of the effects of treating periodontal infection on glycemic control is warranted.

Blood Glucose↗

PubMed1999

Effect of inhibiting HMG-CoA reductase on 7 alpha-hydroxy-4-cholesten-3-one, a marker of bile acid synthesis: contrasting findings in patients with and without prior up-regulation of the latter pathway.

BACKGROUND: Atorvastatin is a potent inhibitor of 3-hydroxy-3-methyl-glutaryl coenzyme A reductase, but its effect on bile acid synthesis is unknown. The objectives of the study were to determine the effect of atorvastatin on bile acid synthesis in patients in whom this process had not been or had been previously up-regulated by pharmacological or surgical means. MATERIALS AND METHODS: Four patients with heterozygous familial hypercholesterolaemia (FH) and partial ileal bypass (PIB) and 19 FH heterozygotes without PIB were treated with placebo, atorvastatin 10 mg and atorvastatin 40 mg daily, each regimen for 4 weeks. The non-PIB group was subsequently treated with bile acid (BA) sequestrant 8-16 g daily followed by co-administration of atorvastatin 10 mg, each for 4 weeks. Plasma 7 alpha-hydroxy-4-cholesten-3-one (7 alpha-HCO), a well-validated marker of BA synthesis was measured using high-performance liquid chromatography with UV detection. RESULTS: The plasma 7 alpha-HCO concentration was tenfold higher with placebo in the PIB than in the non-PIB group (418.5 ng mL-1 vs. 39.6 ng mL-1 p = 0.0001). Levels decreased in PIB patients treated with atorvastatin 10 mg and 40 mg daily (350.1 ng mL-1 and 174.0 ng mL-1, P = 0.007 respectively) but did not change significantly in the non-PIB group (44.7 ng mL-1 and 28.3 ng mL-1 respectively). Administration of BA sequestrant to non-PIB patients increased 7 alpha-HCO to 197.4 ng mL-1; this decreased to 106.0 ng mL-1 during co-administration of atorvastatin 10 mg daily (P = 0.0001). CONCLUSION: Atorvastatin decreases the rate of BA synthesis only if the latter is up-regulated by PIB or BA sequestrants, presumably by limiting the supply of newly synthesized free cholesterol.

Anticholesteremic Agents↗

PubMed1999

High-resolution mapping and histologic examination of long radiofrequency lesions in canine atria.

INTRODUCTION: Catheter ablation may prevent conduction of multiple atrial wavefronts and/or reduce the critical mass of atrial myocardium required to sustain fibrillation. The purpose of this study was to examine the effect of radiofrequency (RF) energy application on conduction in canine atria by performing high-density epicardial mapping and careful histologic examination of the ablation zone. METHODS AND RESULTS: RF energy was applied to the right atrial endocardium in nine anesthetized mongrel dogs in an attempt to create a line of conduction block spanning the vertical length of a 504-channel epicardial mapping plaque. The mean length and width of the histologically determined ablation zone was 34 +/- 4 and 7.3 +/- 2.6 mm, respectively. No thrombus was present. Conduction block that spanned the mapping plaque in 6 of 9 animals was matched histologically by continuous transmural necrosis in five. In one, only a portion of the ablation zone was transmural; the remainder was wide but nontransmural. In 2 of 3 animals with conduction, a narrow region was present where continuous transmural necrosis was absent. In the other animal, conduction was present despite continuous transmural necrosis. CONCLUSION: Conduction block usually occurred when continuous transmural necrosis was present, and conduction usually persisted when continuous transmural necrosis was absent. However, important exceptions were observed, including block when the ablation zone was wide but nontransmural, and conduction despite a thin line of continuous transmural necrosis.

Animals↗

PubMed1999

The prevalence of BANA-hydrolyzing periodontopathic bacteria in smokers.

Smoking has been identified as a risk factor for development of periodontal disease and a strong indicator for treatment failure in periodontal patients. This study examined 172 patients categorized as current smokers (n=55), previous smokers (n=38) or individuals that had never smoked (n=79). A total of 670 interproximal plaques collected with a wooden toothpick were analyzed for hydrolysis of the synthetic trypsin substrate benzoyl-DL-arginine naphthylamide (BANA). About 95% of the BANA hydrolysis by plaque is due to the presence of one or more of the periodontopathogens, P. gingivalis, T. denticola or B. forsythus. Gingival health was measured using the papillary bleeding score (PBS). Current smokers had less gingival bleeding than previous smokers or those who had never smoked (20% versus 41% and 25%, respectively). Plaque removed from non-bleeding sites in current smokers were 11x more likely to have a positive BANA reaction when compared to plaque removed from non-bleeding sites in individuals who never smoked. A significant positive relationship exists between smoking and colonization by the BANA periodontopathogens. Smoking may select for these periodontopathic species in the plaque and may be one reason why smoking is a risk factor in periodontal disease development.

Bacteroides↗

PubMed1999

Factors which are associated with dental decay in the older individual.

OBJECTIVES: To improve reliability of salivary bacterial cultures as a surrogate for plaque levels of cariogenic bacterial species by reporting the salivary CFUs of these organisms as a function of the number of teeth. DESIGN: Cross-sectional collection of data in a convenience sample of adults over 60 years of age. SETTING: Hospital Dental clinic, University bacteriology laboratory. SUBJECTS: 523 older dentate subjects, average age 70, including 412 subjects who were in an independent living status and 111 in a dependent-living situation. MAIN OUTCOME MEASURES: Subjects were examined for decay and the presence of salivary factors including the levels of S. mutans, lactobacilli, yeast and other bacteria. The salivary levels of the bacteria were adjusted for the number of teeth in the mouth, and the resultant values were entered into multivariable logistic regression models along with clinical and other salivary parameters. RESULTS: Mutans streptococci levels reported as CFUs/ml saliva per tooth were significantly associated with coronal surface decay, and lactobacilli, reported in a similar way, were significantly associated with root surface decay. Salivary levels of yeasts, which had previously been associated with decay in this population, were no longer significant using this construct. CONCLUSIONS: This construct of reporting salivary bacteriological data as a function of tooth number and per ml saliva could improve the reliability of bacteriological data obtained in epidemiological studies investigating the role of bacteria in dental decay in the elderly.

Candida↗

PubMed1999

Exposure of N-formyl-L-methionyl-L-leucyl-L-phenylalanine-activated human neutrophils to the Pseudomonas aeruginosa-derived pigment 1-hydroxyphenazine is associated with impaired calcium efflux and potentiation of primary granule enzyme release.

The effects of pathologically relevant concentrations (0.38 to 12.5 microM) of the proinflammatory, Pseudomonas aeruginosa-derived pigment 1-hydroxyphenazine (1-hp) on Ca2+ metabolism and intracellular cyclic AMP (cAMP) in N-formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP; 1 microM)-activated human neutrophils, as well as on the release of myeloperoxidase (MPO) and elastase from these cells, have been investigated in vitro. Ca2+ fluxes were measured by the combination of a fura-2/AM-based spectrofluorimetric method and radiometric procedures, which together enable distinction between net efflux and influx of the cation, while radioimmunoassay and colorimetric methods were used to measure cAMP and granule enzymes, respectively. Coincubation of neutrophils with 1-hp did not affect intracellular cAMP levels or the FMLP-activated release of Ca2+ from intracellular stores but did retard the subsequent decline in the chemoattractant-induced increase in the concentration of cytosolic free Ca2+. These effects of 1-hp on the clearance of Ca2+ from the cytosol of activated neutrophils were associated with decreased efflux of the cation from the cells and increased release of MPO and elastase, while the delayed store-operated influx of the cation into the cells was unaffected by the pigment. The plasma membrane Ca2+-ATPase rather than a Na+-Ca2+ exchanger appeared to be the primary target of 1-hp. These observations suggest that the proinflammatory interactions of 1-hp with activated human neutrophils are a consequence of interference with the efflux of cytosolic Ca2+ from these cells.

Adenosine Triphosphate↗

PubMed1999

Pseudomonas aeruginosa pyocyanin and 1-hydroxyphenazine inhibit fungal growth.

AIM: To examine strains of Pseudomonas aeruginosa for specific antifungal factors. METHODS: Two clinical strains of P aeruginosa with strong in vitro inhibition (by cross streak assay) of Candida albicans and Aspergillus fumigatus were examined. Both strains were isolated from sputum--one from a patient with cystic fibrosis and one from a patient with bronchiectasis. Bacterial extracts were fractionated by high performance liquid chromatography and examined by ultraviolet absorbance and mass spectroscopy. Antifungal activity against C albicans and A fumigatus was determined in a well plate assay. RESULTS: Pyocyanin was the major antifungal agent of P aeruginosa; 1-hydroxy-phenazine also possessed activity. Pyocyanin MICs for C albicans and A fumigatus were > 64 micrograms/ml. These phenazines were active against nine other yeast species pathogenic for man. Preliminary experiments also suggested possible inhibition of yeast mycelial transformation in C albicans by pyocyanin. CONCLUSIONS: There may be a role for pyocyanin and 1-hydroxyphenazine in the prevention of pulmonary candidiasis in patients colonised by P aeruginosa.

Aspergillus fumigatus↗

PubMed1999

Der p 1 facilitates transepithelial allergen delivery by disruption of tight junctions.

House dust mite (HDM) allergens are important factors in the increasing prevalence of asthma. The lung epithelium forms a barrier that allergens must cross before they can cause sensitization. However, the mechanisms involved are unknown. Here we show that the cysteine proteinase allergen Der p 1 from fecal pellets of the HDM Dermatophagoides pteronyssinus causes disruption of intercellular tight junctions (TJs), which are the principal components of the epithelial paracellular permeability barrier. In confluent airway epithelial cells, Der p 1 led to cleavage of the TJ adhesion protein occludin. Cleavage was attenuated by antipain, but not by inhibitors of serine, aspartic, or matrix metalloproteinases. Putative Der p 1 cleavage sites were found in peptides from an extracellular domain of occludin and in the TJ adhesion protein claudin-1. TJ breakdown nonspecifically increased epithelial permeability, allowing Der p 1 to cross the epithelial barrier. Thus, transepithelial movement of Der p 1 to dendritic antigen-presenting cells via the paracellular pathway may be promoted by the allergen's own proteolytic activity. These results suggest that opening of TJs by environmental proteinases may be the initial step in the development of asthma to a variety of allergens.

Allergens↗

PubMed1999

Periodontal disease and risk of fatal coronary heart and cerebrovascular diseases.

BACKGROUND: Recent reports have implicated periodontal disease as a risk factor for coronary heart disease (CHD). METHODS: A retrospective cohort study was conducted using participants in the 1970-1972 Nutrition Canada Survey (NCS). The mortality experience of male and female NCS participants aged 35-84 years without self-reported CHD (n = 10,368) or cerebrovascular disease (CVD) (n = 11,251) was determined through 1993. The relation between dental health and the risk of fatal CHD and CVD was assessed using Poisson regression modeling. RESULTS: In total, 466 CHD and 210 CVD deaths were observed; missing confounder data reduced these numbers to 416 CHD and 182 CVD deaths. Adjusted for age, sex, diabetes status, serum total cholesterol, smoking, hypertensive status, and province, we found a statistically significant association between periodontal disease and risk of fatal CHD. Rate ratios (RR) of 2.15 [95% confidence interval (CI) 1.25-3.72) and 1.90 (95% CI 1.17-3.10) were observed for severe gingivitis and edentulous status, respectively. Non-statistically significantly increased RRs of 1.81 and 1.63 were observed for severe gingivitis and edentulous status for CVD. CONCLUSIONS: These data indicate that poor dental health is associated with an increased risk of fatal CHD.

Adult↗

PubMed1999

Determining dental checkup frequency.

BACKGROUND: The authors assessed the dental checkup frequency of adults living in the Detroit tricounty area and identified demographic, access and subjective factors associated with visits to a dentist made not because of a dental problem. METHODS: Data are from a 1994 probability-based sample of adults who were interviewed and received an in-home oral examination. The authors used the variables of age, sex, education level, income level, dental insurance status, usual place for care, objective measures of oral health, and subjective assessments of health, pain and dental anxiety to predict the frequency of dental checkups. RESULTS: The authors found that differences in dental checkup behavior were related to demographics, access to dental care, subjective ratings of oral and general health and other self-assessments, and clinical parameters of oral health. In multiple logistic regression analysis considering all variables simultaneously, sex, income, having a usual place for care and level of dental care anxiety were found to be associated with having dental checkups. The authors determined the statistical significance level at P < .05. CONCLUSIONS: A total of 69.7 percent of the study population reported having had a dental checkup at least once a year in the past five years. The authors found that four factors associated with infrequent dental checkups: being male, having lower income levels, not having a usual place for care and being anxious about receiving dental care. PRACTICE IMPLICATIONS: Dental health professionals should consider the correlates of dental checkup frequency identified in this study and the usefulness of proposed strategies to increase and sustain regular preventive visitation patterns in their own patient populations.

Adolescent↗

PubMed1999

Role of metabotropic glutamate receptors in epilepsy.

Considerable information is available regarding the role of ionotropic glutamate receptors in the generation of interictal spikes. Progress in the study of metabotropic glutamate receptors (mGluRs) makes clear that activation of these receptors can contribute greatly to seizure discharges and epileptogenesis. The effects of activation of the different mGluR subgroups on neuronal hypersynchrony and the initiation and propagation of seizure discharges in hippocampal slices are discussed herein. To help one understand the mechanisms that underlie these effects, information regarding the action of mGluRs on cellular and synaptic properties is summarized. The data bring to the forefront the critical role of mGluRs in epilepsy and emphasize the anticonvulsant effects of group II and III mGluR activation as opposed to the convulsant action of group 1, which elicits seizure discharges and epileptogenesis in experimental models.

Action Potentials↗

PubMed1998

Cholesterol synthesis is increased in mixed hyperlipidaemia.

We showed previously that hypertriglyceridaemia, but not hypercholesterolaemia, is correlated with increases in cholesterol synthesis and apolipoprotein B secretion in patients with secondary hypertriglyceridaemia. The aim of the present study was to compare the rate of cholesterol synthesis, using fasting plasma mevalonic acid (MVA) as an index, in patients with primary mixed hyperlipidaemia (type IIb phenotype, n=45) and primary hypercholesterolaemia (type IIa phenotype, n=92). LDL cholesterol was significantly higher in types IIa (6.38+/-0.18 mmol/l) and IIb (5.89+/-0.25 mmol/l) compared to 40 normolipidaemic controls (2. 99+/-0.1 mmol/l, P<0.0001), whereas serum triglyceride was higher in type IIb (2.62 (range 2.2-3.0) mmol/l) than type IIa (1.22 (range 0. 85-1.60) mmol/l, P<0.001) and controls (0.90 (range 0.68-1.24) mmol/l, P<0.001). Similarly, MVA was higher in type IIb (7.0+/-0.46 ng/ml) than IIa (5.6+/-0.23 ng/ml, P<0.0) and controls (5.6+/-0.36 ng/ml, P<0.05). Plasma MVA correlated positively with serum triglyceride (r=0.22, P=0.004) and negatively with LDL cholesterol (r=-0.21, P=0.014). These results are in accordance with previous observations that VLDL-apolipoprotein B secretion and cholesterol synthesis are linked and demonstrate that the latter is increased in mixed hyperlipidaemia.

Adult↗

PubMed1998

Increased efficiency of analyses: cumulative logistic regression vs ordinary logistic regression.

The common practice of collapsing inherently continuous or ordinal variables into two categories causes information loss that may potentially weaken power to detect effects of explanatory variables and result in Type II errors in statistical inference. The purpose of this investigation was to illustrate, using a substantive example, the potential increase in power gained from an ordinal instead of a dichotomous specification for an inherently continuous response. Ordinary (OLR) and cumulative logistic regression (CLR) modeling were used to test the hypothesis that the risk of alveolar bone loss over 2 years is greater for subjects with poorer control of non-insulin-dependent diabetes mellitus (NIDDM) than for those who do not have diabetes or have better controlled NIDDM. There were 359 subjects; 21 of whom had NIDDM. Analysis of main effects using OLR for the dichotomous outcome (no change in radiographic bone loss vs any change) produced parameter estimates for better control and poorer control that were not statistically significant. CLR analysis of main effects using a 4-category ordinal specification for radiographic bone loss also produced a parameter estimate for better control that was not statistically significant, but which estimated poorer control to have a significant effect. The fit of this CLR model was significantly better at P < 0.05 than that for the OLR. While an OLR model testing the interaction between age and control status did not converge after 100 iterations, the CLR interaction model converged without difficulty and estimated a significant effect for interaction between age and poorer control. Results from the CLR analysis, in contrast to the OLR model, would lead one to conclude that the risk for more severe bone loss progression after 2 years is greater in subjects with poorer controlled NIDDM and that subjects with better controlled NIDDM may not have greater risk of bone loss progression than those without diabetes. The use of an ordinal instead of a dichotomous specification for an inherently continuous response provided increased power, more precise parameter estimates, and a significantly better fitting model. In estimating parameter estimates for odds ratios or risks, it is important to consider using ordinal logistic regression where the response is inherently continuous or ordinal.

Adolescent↗