Biomedical subjects

G W Taylor

Publications and source records attributed to G W Taylor.

At least 55 records · Page 3Linked to original sources

PubMed1998

Glycemic control and alveolar bone loss progression in type 2 diabetes.

This study tested the hypothesis that the risk for alveolar bone loss is greater, and bone loss progression more severe, for subjects with poorly controlled (PC) type 2 diabetes mellitus (type 2 DM) compared to those without type 2 DM or with better controlled (BC) type 2 DM. The PC group had glycosylated hemoglobin (HbA1) > or = 9%; the BC group had HbA1 < 9%. Data from the longitudinal study of the oral health of residents of the Gila River Indian Community were analyzed. Of the 359 subjects, aged 15 to 57 with less than 25% radiographic bone loss at baseline, 338 did not have type 2 DM, 14 were BC, and 7 were PC. Panoramic radiographs were used to assess interproximal bone level. Bone scores (scale 0-4) corresponding to bone loss of 0%, 1% to 24%, 25% to 49%, 50% to 74%, or > or = 75% were used to identify the worst bone score (WBS) in the dentition. Change in worst bone score at follow-up, the outcome, was specified on a 4-category ordinal scale as no change, or a 1-, 2-, 3-, or 4-category increase over baseline WBS (WBS1). Poorly controlled diabetes, age, calculus, time to follow-up examination, and WBS1 were statistically significant explanatory variables in ordinal logistic regression models. Poorly controlled type 2 DM was positively associated with greater risk for a change in bone score (compared to subjects without type 2 DM) when the covariates were included in the model. The cumulative odds ratio (COR) at each threshold of the ordered response was 11.4 (95% CI = 2.5, 53.3). When contrasted with subjects with BC type 2 DM, the COR for those in the PC group was 5.3 (95% CI = 0.8, 53.3). The COR for subjects with BC type 2 DM was 2.2 (95% CI = 0.7, 6.5), when contrasted to those without type 2 DM. These results suggest that poorer glycemic control leads to both an increased risk for alveolar bone loss and more severe progression over those without type 2 DM, and that there may be a gradient, with the risk for bone loss progression for those with better controlled type 2 DM intermediate to the other 2 groups.

Adolescent↗

PubMed1998

Non-insulin dependent diabetes mellitus and alveolar bone loss progression over 2 years.

This study tested the hypothesis that persons with non-insulin dependent diabetes mellitus (NIDDM) have greater risk of more severe alveolar bone loss progression over a 2-year period than those without NIDDM. Data from the longitudinal study of the oral health of residents of the Gila River Indian Community were analyzed for 362 subjects, aged 15 to 57, 338 of whom had less than 25% radiographic bone loss at baseline, and who did not develop NIDDM nor lose any teeth during the 2-year study period. The other 24 subjects had NIDDM at baseline, but met the other selection criteria. Bone scores (scale 0-4) from panoramic radiographs corresponded to bone loss of 0%, 1%-24%, 25%-49%, 50%-74%, or 75% and greater. Change in bone score category was computed as the change in worst bone score (WBS) reading after 2 years. Age, calculus, NIDDM status, time to follow-up examination, and baseline WBS were explanatory variables in regression models for ordinal categorical response variables. NIDDM was positively associated with the probability of a change in bone score when the covariates were controlled. The cumulative odds ratio for NIDDM at each threshold of the ordered response was 4.23 (95% C.I. = 1.80, 9.92). In addition to being associated with the incidence of alveolar bone loss (as demonstrated in previous studies), these results suggest an NIDDM-associated increased rate of alveolar bone loss progression.

Adolescent↗

PubMed1997

Glutathione and neonatal lung disease.

Glutathione (GSH) was measured using HPLC-electrochemical detection in bronchoalveolar lavage fluid from 28 neonates for up to 21 days after birth. GSH levels varied from 0.1-11.2 mumol l-1 (with a geometric mean concentration of 1.3 mumol l-1). GSH in epithelial lining fluid was estimated using the urea dilution method at 15.0 mumol l-1 (range 0.5-196 mumol l-1), which is significantly lower than observed in adult subjects. There was an L shaped relationship between GSH and the two markers of oxygen therapy, oxygen index and FiO2. The lowest GSH levels were associated with the group of infants with the most severe airways problems who required high oxygen.

Bronchoalveolar Lavage Fluid↗

PubMed1997

Analysis of terfenadine in human plasma using microbore high-performace liquid chromatography-electrospray ionisation mass spectrometry.

An assay based on combined microbore high-performance liquid chromatography-positive ion electrospray ionisation mass spectrometry with selected ion recording has been developed for the measurement of the antihistamine drug terfenadine in human plasma. A deuterated analogue of terfenadine was synthesised for use as an internal standard and extraction of terfenadine was carried out on C18 solid phase extraction columns. The limit of detection of terfenadine in plasma is 0.1 ng/ml and the intra-assay coefficient of variation at 1 ng/ml is 10.1%. Plasma concentrations of terfenadine measured in six normal subjects following a 120 mg oral dose are reported.

Anti-Allergic Agents↗

PubMed1997

Electrospray mass spectrometric characterization of a corticosteroid dimer.

18-Hydroxy-11-deoxycorticosterone forms a non-polar dimer under acidic conditions. The dimer was purified by high performance liquid chromatography and further analysed by electrospray mass spectrometry. The purified dimer has a molecular weight of 656 Da with two free ketone groups and no free hydroxyl functions. The mass spectrometric data suggest a 20,21,20',21'-anhydro dimer structure for the dimer. Microbore high performance liquid chromatography/electrospray mass spectrometry of rat adrenal extracts indicated that both 18-OH-B and 18-OH-DOC were present, although no 18-OH-DOC dimer was detected.

Adrenal Cortex Hormones↗

PubMed1997

Arginine-specific mono(ADP-ribosyl)transferase activity in human neutrophil polymorphs. A possible link with the assembly of filamentous actin and chemotaxis.

Mono(ADP-ribosyl)transferase activity has been detected on the external surface of human polymorphonuclear neutrophil leucocytes (PMNs). The corresponding cDNA has been cloned and shown to be identical to that derived from human skeletal muscle. Our results suggest that mono(ADP-ribosyl)transferase is involved in the transduction pathway mediating (i) receptor-dependent re-alignment of cytoskeletal actin and (ii) chemotaxis of PMNs.

ADP Ribose Transferases↗

PubMed1997

The cardiac effects of terfenadine after inhibition of its metabolism by grapefruit juice.

OBJECTIVE: To determine whether the pharmacokinetics and electrocardiographic pharmacodynamics of terfenadine are affected by the concomitant administration of grapefruit juice. METHODS: Six healthy volunteers were recruited for a balanced cross-over study. Each volunteer received 120 mg terfenadine 30 min after drinking 300 ml of either water or freshly squeezed grapefruit juice. The alternative treatment was administered on the second study day 2 weeks later. Measurements of the area under the terfenadine plasma concentration-time curve (AUC), maximum terfenadine concentration (Cmax) and the time to maximum concentration (tmax) were made, and the corrected QT (QTc) interval was measured from the surface electrocardiogram. RESULTS: Terfenadine was quantifiable in plasma in all 6 subjects on both study days for up to 24 h post-dosing. The AUC of terfenadine was significantly increased by concomitant grapefruit administration (median values 40.6 vs 16.3 ng.ml-1.h), as was the Cmax (median values 7.2 vs 2.1 ng.ml-1). The tmax was not significantly increased and there was no significant change in the median QTc interval despite the increased terfenadine levels. The 95% confidence interval for the difference in the change in QTc interval at Cmax was -13 to +38 ms. CONCLUSION: Administration of grapefruit juice concomitantly with terfenadine may lead to an increase in terfenadine bioavailability, but the increase observed in this study did not lead to significant cardiotoxicity in normal subjects. However, this does not exclude the risk of cardiotoxicity in high-risk subjects given greater doses of grapefruit juice over longer periods of time.

Adult↗

PubMed1997

MRI of car occupants with whiplash injury.

Our purpose was to document and investigate the prognostic significance of features seen on MRI of patients with whiplash injury following relatively minor road traffic crashes. MRI was obtained shortly and at 6 months after the crash using a 0.5 T imager. The images were assessed independently by two radiologists for evidence of fracture or other injury; loss of lordosis and spondylosis were also recorded. Clinical examinations were used to assess the status of patients initially and at 6 months. The results of the independent MRI and clinical investigations were then examined for association using statistical tests. Initial MRI was performed on 29 patients, of whom 19 had repeat studies at 6 months; 48 examinations were thus examined. Apart from spondylosis and loss of lordosis, only one abnormality was detected: an intramedullary lesion consistent with a small cyst or syrinx. There were no statistically significant associations between the outcome of injury and spondylosis or loss of lordosis. No significant changes were found when comparing the initial and follow-up MRI. It appears that MRI of patients with relatively less severe whiplash symptoms reveals a low frequency of abnormalities, apart from spondylosis and loss of lordosis, which have little short-term prognostic value. Routine investigation of such patients with MRI is not justified in view of the infrequency of abnormalities detected, the lack of prognostic value and the high cost of the procedure.

Accidents, Traffic↗

PubMed1997

Upregulation of cholesterol synthesis after acute reduction of low density lipoprotein by apheresis in normocholesterolaemic subjects: evidence for a threshold effect.

The influence of low density lipoproteins (LDL) in the plasma on the regulation of cholesterol biosynthesis is not clear. We studied the changes in plasma mevalonic acid (MVA) concentration and the lathosterol/cholesterol (L/C) ratio, which are well established indices of whole body cholesterol synthesis, in four normocholesterolaemic subjects after each had undergone LDL apheresis on two occasions. LDL apheresis of 75% of the calculated plasma volume reduced LDL-cholesterol by 44% to 1.5 +/- 0.2 mmol/l without changing plasma MVA levels or L/C ratios. Apheresis of 125% of the calculated plasma volume decreased plasma LDL-cholesterol by 69% to 0.9 +/- 0.2 mmol/l, with significant increases in plasma MVA and L/C ratio on the day after the procedure. These results imply that LDL-cholesterol is an integral part of the sterol regulatory pool and suggest that plasma levels cannot be lowered below 1-1.4 mmol/l in normal subjects without upregulating cholesterol biosynthesis.

Adult↗

PubMed1997

Effect of the isoprostanes, 8-iso prostaglandin E2 and 8-iso prostaglandin F2 alpha on the rabbit lung in vivo.

8-Iso-prostaglandin (PG)E2 and 8-iso-PGF2 alpha are members of the isoprostane class of prostanoids which are formed by free radical mediated oxidation of arachidonic acid. Both E2- and F2-isoprostanes are potent vasoconstrictors and are believed to act through the prostanoid TP-receptors or a closely related receptor. In lightly anaesthetised, spontaneously breathing rabbits, aerosolised administration of histamine (1.25-40 mg ml-1, n = 8) caused a modest dose-dependent increase in total lung resistance (RL) and a concomitant fall in dynamic lung compliance (CL dyn). Aerosolised methacholine (0.625-20 mg ml-1, n = 6) caused considerable bronchoconstriction, with a dose-dependent increase in RL, and a corresponding fall in CL dyn. In contrast, intratracheal administration of either 8-iso PGE2 or 8-iso-PGF2 alpha (1 ng ml(-1)-100 micrograms ml-1, n = 8) had no significant effect on lung function. The TP-receptor agonist, U-46619, was similarly inactive in this model when given by aerosol. Intravenous administration of histamine or 8-iso PGF2 omega had no significant effect on the lung indices, RL and CL dyn, or on the pulmonary and systemic vasculature (n = 4 per drug group). 8-Iso-PGE2 caused a concentration-dependent decrease in the right ventricular systolic pressure from 3 nmol kg-1 to 100 nmol kg-1 (n = 43, p < 0.05), but showed no other activity. In contrast, U-46619 given intravenously caused an increase in transpulmonary pressure (n = 4, p < 0.05), but had no effect on airflow. At higher doses, it did cause a significant drop in both systemic and right ventricular systolic pressures (n = 4, p < 0.05), which were probably due to an interaction with platelets. The isoprostanes had no effect on the rabbit airway up to a concentration of 3 microM. In contrast, 3 microM U-46619 caused a modest contraction of tracheal smooth muscle, whilst 3 microM methacholine was at least five-fold more potent in contracting the same tissues. We conclude that the aerosolised isoprostanes are not broncho-constricting agents in the rabbit in vivo.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

PubMed1997

The optimization of the BANA test as a screening instrument for gingivitis among subjects seeking dental treatment.

Porphyromonas gingivalis, Treponema denticola and Bacteroides forsythus have been implicated in periodontal disease and each possesses an enzyme capable of hydrolyzing the synthetic trypsin substrate, BANA. We have used a chairside test for BANA hydrolysis to diagnose an anaerobic periodontal infection in patients with advanced forms of clinical disease using a 15-min/55 degrees C incubation protocol. However, the BANA test performance is dependent upon the length and temperature of incubation. In the present study, we have evaluated a 5-min/35 degrees C, a 5-min/55 degrees C and a 15-min/55 degrees C incubation protocol to determine whether the performance of the BANA test could be optimized using plaque samples obtained from subjects seeking dental treatment. Logistic regression models were tested with age, smoking status, and gingivitis scores as covariates. The best fitting model obtained with the 5-min/35 degrees C protocol had a sensitivity of 71%, a specificity of 68%, a false-positive proportion of 9%, a false-negative proportion of 65%, and an overall accuracy of 80%. When maximum likelihood estimates were obtained in this model, plaques from individuals who reported that they currently smoked were 9.57x, and those who quit smoking were 4.73x more likely to have a positive BANA score than someone who never smoked. Plaques were 4.55x more likely to be BANA-positive if they were removed from sites with gingivitis. These findings indicate that the performance of the BANA test is best using the 5-min/35 degrees C incubation protocol.

Adolescent↗

PubMed1997

Evaluation and use of an index of oral health status.

OBJECTIVES: The goals of this investigation were (1) to evaluate the Oral Health Status Index in relation to demographic characteristics, socioeconomic status, and preventive behaviors of an adult population; and (2) to understand how individual index components performed as indicators of oral health status compared to the composite index. METHODS: The Oral Health Status Index (OHSI) was used on a probability sample of adults, aged 18-93 years, living in the Detroit tricounty area. Data were collected on 509 subjects via in-home dental examinations. Bivariate and multivariate analyses were used to compare the OHSI and its components, including decayed, missing, and replaced teeth, free ends, and moderate and severe periodontal disease measures. RESULTS: The mean OHSI score for subjects was 77.3 (SE = 1.83) with a range of -8.0 to 100.0. In regression analyses, OHSI scores were positively correlated with subjects' education level, self-rated oral health scores, and frequency of dental checkups and negatively correlated with age, nonwhite race, and smoking. Of the index components, missing teeth performed well as an indicator of oral health status. Missing teeth were positively correlated with age, nonwhite race, and smoking and negatively correlated with education level, self-rated oral health, and use of Medicaid. About 53 percent of variance in OHSI scores was explained by the multivariate models, compared to 46 percent for missing teeth. CONCLUSIONS: Choosing an indicator of oral health status likely will depend upon the characteristics of the population to be studied. As a composite measure of oral health status, the OHSI performed acceptably; however, missing teeth, an index component, also worked well. Continued evaluation of the OHSI is warranted.

Adolescent↗

PubMed1997

Effect of salmeterol on Pseudomonas aeruginosa infection of respiratory mucosa.

We have studied the effect of salmeterol on both P. aeruginosa interactions with the mucosa of nasal turbinate organ cultures and on pyocyanin-induced (20 microg/ml) and elastase-induced (100 microg/ml) damage to nasal epithelial cells. Organ cultures were exposed to salmeterol either by preincubation with 4 x 10(-7) M salmeterol for 30 min or by pipetting 20 microl of 4 x 10(-7) M salmeterol onto the organ culture surface immediately prior to bacterial inoculation. Infected organ cultures (8 h) had significantly (p < or = 0.01) increased epithelial damage, and P. aeruginosa was predominantly associated with damaged epithelium and mucus. Salmeterol significantly (p < or = 0.02) reduced epithelial damage caused by infection and the total number of adherent bacteria (p < or = 0.05), but bacterial distribution on the mucosa was unchanged. Nasal epithelial cells incubated with pyocyanin (20 microg/ml) or elastase (100 microg/ml) for 3 h had significantly (p < or = 0.05) increased cytoplasmic blebbing and mitochondrial damage versus control values. Elastase also significantly (p < or = 0.05) increased cell projection and reduced the level of ciliation. Cells preincubated with salmeterol (2 x 10(-7) M) showed a significant reduction in some features of cell damage caused by both toxins, which was inhibited by the beta2-adrenoceptor antagonist propranolol. Our results indicate that salmeterol reduces P. aeruginosa-induced damage to both organ culture and nasal epithelium.

Adrenergic beta-Agonists↗

PubMed1997

Urinary leukotriene E4 levels in patients with atopic dermatitis.

Leukotriene synthesis may be increased in a variety of inflammatory diseases. Urinary leukotriene E4 is a stable metabolite of leukotrienes C4 and D4 which has previously been found to be increased in exacerbations of severe asthma and after antigen inhalation. Levels of urinary LTE4 in seven patients during and after a severe flare of atopic dermatitis were measured by high-performance liquid chromatography (HPLC) and radioimmunoassay (RIA). Mean urinary LTE4 levels (+/- SEM) were not increased during (16.7 +/- 3.7 pg/mumol) or after (16.9 +/- 4.8 mumol) the acute exacerbation of atopic dermatitis when compared with the normal range (mean = 23.8 [95% confidence interval 19.9-28.2] pg/mumol creatinine). These findings do not provide evidence of cysteine leukotriene involvement in the pathogenesis of atopic dermatitis.

Acute Disease↗

PubMed1997

Prolonged inhibition of cholesterol synthesis explains the efficacy of atorvastatin.

HMG-CoA reductase inhibitors or statins are effective in both the primary and secondary prevention of coronary heart disease, the extent of benefit being proportional to the reduction in low density lipoprotein (LDL) cholesterol achieved. Atorvastatin, a newly licensed compound, reportedly lowers LDL with greater efficacy than other statins. The mechanism of this action was, therefore, explored in twenty patients with refractory familial hypercholesterolemia who received in a single-blind sequence simvastatin 40 mg/day, placebo and atorvastatin 10 mg/day each for 4 weeks. At the end of the placebo period the effects of single 40-mg doses of simvastatin and atorvastatin on plasma levels and urinary excretion of mevalonic acid, indices of HMG-CoA reductase activity, were compared. Administration of atorvastatin 10 mg daily for 1 month lowered LDL cholesterol by 32.5%, compared with placebo (P = 0.0001), which was 4.5% less than the decrease after simvastatin 40 mg daily (P = 0.33). The area under the plasma curve and urinary mevalonic acid/ creatinine ratio were both significantly less during the 24 h after a single dose of atorvastatin 40 mg than after a single dose of simvastatin 40 mg (P < 0.01). These findings suggest that the greater efficacy of atorvastatin compared with simvastatin is due to more prolonged inhibition of HMG-CoA reductase, presumably reflecting longer residence of atorvastatin or its active metabolites in the liver.

Anticholesteremic Agents↗

PubMed1996

Arginine-specific mono(ADP-ribosyl)transferase activity on the surface of human polymorphonuclear neutrophil leucocytes.

An Arg-specific mono(ADP-ribosyl)transferase activity on the surface of human polymorphonuclear neutrophil leucocytes (PMNs) was confirmed by the use of diethylamino-(benzylidineamino)guanidine (DEA-BAG) as an ADP-ribose acceptor. Two separate HPLC systems were used to separate ADP-ribosyl-DEA-BAG from reaction mixtures, and its presence was confirmed by electrospray mass spectrometry. ADP-ribosyl-DEA-BAG was produced in the presence of PMNs, but not in their absence. Incubation of DEA-BAG with ADP-ribose (0.1-10 mM) did not yield ADP-ribosyl-DEA-BAG, which indicates that ADP-ribosyl-DEA-BAG formed in the presence of PMNs was not simply a product of a reaction between DEA-BAG and free ADP-ribose, due possibly to the hydrolysis of NAD+ by an NAD+ glycohydrolase. The assay of mono(ADP-ribosyl)transferase with agmatine as a substrate was modified for intact PMNs, and the activity was found to be approx. 50-fold lower than that in rabbit cardiac membranes. The Km of the enzyme for NAD+ was 100.1 30.4 microM and the Vmax 1.4 0.2 pmol of ADP-ribosylagmatine/h per 10(6) cells. The enzyme is likely to be linked to the cell surface via a glycosylphosphatidylinositol anchor, since incubation of intact PMNs with phosphoinositol-specific phospholipase C (PI-PLC) led to a 98% decrease in mono(ADP-ribosyl)transferase activity in the cells. Cell surface proteins were labelled after exposure of intact PMNs to [32P]NAD+. Their molecular masses were 79, 67, 46, 36 and 26 kDa. The time course for labelling was non-linear under these conditions over a period of 4 h. The labelled products were identified as mono(ADP-ribosyl)ated proteins by hydrolysis with snake venom phosphodiesterase to yield 5'-AMP.

ADP Ribose Transferases↗

PubMed1996

Plasma mevalonic acid, an index of cholesterol synthesis in vivo, and responsiveness to HMG-CoA reductase inhibitors in familial hypercholesterolaemia.

Fasting plasma mevalonic acid (MVA), an indicator of in vivo cholesterol synthesis, was measured in 35 patients with familial hypercholesterolaemia (FH) of whom 7 were treated with pravastatin 10-40 mg/day, 7 with simvastatin 10-40 mg/day and 21 with atorvastatin 80 mg/day. Reductions in low density lipoprotein (LDL) cholesterol and MVA on maximal dose therapy differed significantly between the three drugs: 34.7%, 42.9% and 54.0% (P = 0.0001), and 31.6%, 48.9% and 58.8% (P = 0.004), respectively. Patients on atorvastatin were subdivided according to whether their reduction in LDL cholesterol on treatment was above or below the mean percentage change for the whole group. Basal values of LDL cholesterol did not differ significantly, but above average responders had a significantly higher mean pre-treatment level of MVA (6.2 +/- 0.60 vs. 4.3 +/- 0.61 ng/ml, P < 0.05) than below average responders. When all three drug groups were pooled above average responders showed a significantly greater absolute decrease in MVA on treatment than below average responders (3.85 +/- 0.48 vs. 2.33 +/- 0.40 ng/ml, P < 0.05). However, there was no significant correlation between the magnitude of the decreases in LDL cholesterol and MVA. These findings suggest that FH patients who responded well to statins had a higher basal level of plasma MVA, i.e. a higher rate of cholesterol synthesis, which was more susceptible to pharmacological inhibition. The more marked cholesterol lowering effect of atorvastatin 80 mg/day presumably reflects, at least in part, its ability to inhibit HMG-CoA reductase to a greater extent than maximal recommended doses of pravastatin and simvastatin of 40 mg/day.

Adult↗

PubMed1996

The effect of bacterial toxins on levels of intracellular adenosine nucleotides and human ciliary beat frequency.

Toxins that slow ciliary beat are virulence determinants of bacteria that infect or invade ciliated epithelial surfaces. We have previously shown that the effect of the Pseudomonas aeruginosa toxin pyocyanin on ciliary beat is associated with a fall in intracellular cAMP and ATP. We have now investigated whether reduction in intracellular adenosine nucleotides might be a common mechanism of action of other bacterial toxins which slow ciliary beat. Two other P. aeruginosa toxins, 1-hydroxyphenazine (1-HP) and rhamnolipid, and two Haemophilus influenzae fractions produced by gel filtration of broth cultures were tested. The effect on human nasal epithelium ciliary beat frequency (CBF), and intracellular cAMP and ATP were measured, and the effect of two pharmacological agents, dibutyryl cAMP and salmeterol, on these changes was assessed. 1-HP, rhamnolipid and the two H. influenzae fractions slowed CBF before there was significant release of lactate dehydrogenase from the cells. The toxins also caused a fall in intracellular cAMP and ATP. Dibutyryl cAMP and salmeterol at the concentrations used do not increase baseline CBF, but diminished the fall in CBF and intracellular adenosine nucleotides. The cAMP and ATP levels in these studies were combined with those previously obtained with pyocyanin. there was a good correlation between cAMP and ATP levels and CBF. Bacterial toxins which slow CBF may act by causing a fall in intracellular adenosine nucleotides, and agents which stimulate cAMP may prevent toxin-induced slowing of ciliary beat.

Adenine Nucleotides↗