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Biomedical subjects

R B Cole

Publications and source records attributed to R B Cole.

At least 19 recordsLinked to original sources
PubMed1995

Determination of amino acids by on-line capillary electrophoresis-electrospray ionization mass spectrometry.

On-line capillary electrophoresis-electrospray ionization mass spectrometry (CE-ESMS) has been used for the separation and detection of amino acid mixtures. Four natural amino acids, histidine, tryptophan, phenylalanine, aspartic acid, and a tripeptide, glutathione, were separated and determined. Protonated molecules were detected in the CE-ESMS mode with detection limits of about one pmol. Optimum CE-ESMS operating conditions for amino acid analysis were determined employing acetic acid solutions as CE electrolytes. The examined parameters included capillary diameter (50-100 microns internal diameter), applied separation voltage (20-30 kV), and concentration of electrolyte (10-60% acetic acid). Stable working conditions were maintained when the CE currents were less than 18 microA. The use of electrolyte solutions such as those described here instead of true buffer solutions may have advantages for CE-ESMS systems which employ a "sheathless" interface.

Amino Acids↗
PubMed1994

Evaluation of a novel hydrophilic derivatized capillary for protein analysis by capillary electrophoresis-electrospray mass spectrometry.

A new type of hydrophilic derivatized capillary has been used to enable the on-line capillary electrophoresis separation and electrospray mass spectrometric detection of a mixture of proteins containing bovine cytochrome c, tuna cytochrome c and horse heart myoglobin. Less than 40 fmol of each compound were loaded into the capillary. Baseline resolution of components was achieved, as were accurate assignments of molecular masses. The hydrophilic derivatized capillaries were taken through extensive testing procedures to characterize their performance and capabilities for protein analysis. A mixture of six proteins (cytochrome c, ribonuclease A, alpha-chymotrypsinogen, myoglobin, carbonic anhydrase II and alpha-lactalbumin) in acetic acid-sodium acetate buffer was used to delineate the relationships between migration time and pH, along with migration time and buffer concentration for each protein. The variations in capillary efficiency as a function of pH and as a function of buffer concentration were also characterized for the same six proteins in the acetic acid-sodium acetate system. A pH of 4.8 was found to offer an excellent compromise between separation efficiency (up to 500,000 theoretical plates) and analysis time. Capillary efficiencies were also found to be very good when employing a Tris.HCl electrolyte adjusted to pH 4.8. Lastly, electropherogram reproducibility and capillary durability were examined with the finding that little deterioration of the capillary occurred over the course of 400 injections (200 h run time). This represents a notable improvement over previously documented derivatization procedures designed to reduce protein adsorption to fused-silica capillary walls.

Animals↗
PubMed1994

Disposition of warfarin enantiomers and metabolites in patients during multiple dosing with rac-warfarin.

1. The disposition of warfarin enantiomers and metabolites has been studied in 36 patients receiving chronic rac-warfarin therapy, titrated to approximately the same anticoagulant response. 2. A stereoselective h.p.l.c. assay was employed to determine the concentrations of (R)- and (S)-warfarin, (R,S)-warfarin alcohol and (S)-7-hydroxywarfarin in plasma and 24 h urine samples. The concentrations of (R)-7-hydroxywarfarin, (S,S)-warfarin alcohol and (R)-6- and (S)-6-hydroxywarfarin were also determined in urine samples. The fractions unbound of warfarin enantiomers were determined using equilibrium dialysis. 3. Wide variability was observed in daily dose requirements (mean 6.1 mg; range: 2.5-12 mg), in plasma concentrations of (S)-warfarin (0.48 mg l(-1); 0.11-1.02 mg l(-1)), (R)-warfarin (0.87 mg l(-1); 0.29-1.82 mg l(-1)), (R,S)-warfarin alcohol (0.31 mg l(-1); 0.02-0.72 mg l(-1)) and (S)-7-hydroxywarfarin (0.25 mg l(-1); 0.07-0.37 mg l(-1)) and the percentage unbound of (S)-warfarin (0.53%; 0.29%-0.82%) and (R)-warfarin (0.54%; 0.26%-0.96%). 4. The mean plasma clearances of warfarin enantiomers were 7.5 1 day-1 per 70 kg (2.5-22.1) for (S)-warfarin and 3.6 1 day-1 per 70 kg (1.6-8.8) for (R)-warfarin. There was a significant correlation between the estimated formation clearance of (S)-7-hydroxywarfarin and the clearance of (S)-warfarin, which accounted for much of the variability in the latter.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Surface-induced dissociation of protonated peptides: implications of initial kinetic energy spread.

Surface-induced dissociation (SID) has been used to produce daughter ion spectra of small protonated peptides generated by fast atom bombardment (FAB). The relative abundances of daughter ions depends critically upon the energy of the ion/surface collision. A wide array of decomposition processes may be observed using ELAB collision energies in the range 10-20 eV. At approximately 13-eV collision energy, the variety of decomposition processes is maximized for the small peptides studied; hence, maximum structural information may be deduced. Collisionally-activated dissociations (CAD) using argon gas and the identical protonated peptides could not produce as large an array of daughter ions in a constant condition experiment. An apparent contradiction is thereby posed because SID is known to produce a narrow distribution of ion internal energies relative to CAD. This apparent contradiction is resolved by considering the rather large kinetic energy spread of ions leaving the FAB source. For the SID process, this large initial kinetic energy distribution is converted into a significantly wider spread in center-of-mass collision energy, leading to a broader variety of decomposition processes (high and low energy) compared to CAD.

Amino Acid Sequence↗
PubMed1992

252Cf plasma-desorption mass spectrometry of lipid A from Enterobacter agglomerans.

Endotoxins from gram-negative bacteria are believed to be causative agents of byssinosis, an occupational pulmonary disease associated with exposure to cotton dust in textile mills. Lipid A preparations from Enterobacter agglomerans, a gram-negative bacterium commonly found in cotton and cotton dust, have been analyzed using plasma-desorption mass spectrometry. Results indicate the existence of at least two lipid A types which differ only by the presence of an additional oxygen atom whose position has been localized to the acyloxyacyl ester-linked side-chain of the distal portion of the molecule. The lower molecular weight compound of the two structures has the same molecular weight and presumably the same empirical formula as a well-characterized lipid A from Salmonella minnesota. The mass spectra of lipid A compounds obtained from S. minnesota and E. agglomerans show strong similarities. Palmitoyl, hydroxymyristoyl, myristoyl, and lauroyl side-chains which are known to be present in the former are inferred from spectral evidence to be present in the latter.

Californium↗
PubMed1990

The use of probenecid to increase the serum amoxycillin levels in patients with bronchiectasis.

Amoxycillin 3 g twice daily is effective in treating patients with bronchiectasis who have daily purulent sputum. However, it is a relatively expensive treatment if used for prolonged periods. This pilot study in six patients with bronchiectasis showed that the concurrent administration of probenecid with a smaller dose of amoxycillin produced similar clinical responses and pharmacokinetic profiles to those found with high dose amoxycillin alone. The amount of amoxycillin used was reduced by two thirds, producing a potential saving of approximately pound 1000 per patient per annum in those taking long term treatment.

Adult↗
PubMed1990

A single oral dose method for predicting steady state theophylline concentrations in clinical practice.

A single dose, single point method of predicting patients' oral maintenance theophylline dosage has been compared with a noninvasive method. Twenty patients with obstructive lung disease received an oral dose (6 mg kg-1) of micro-crystalline theophylline. The plasma theophylline concentration after 8-10 h was then used to calculate the optimum maintenance dose of sustained release aminophylline required to achieve steady state concentrations between 55 and 110 mumols l-1. The mean steady state plasma theophylline concentration for this dosage schedule was also predicted by a method using population average pharmacokinetic parameters (assumed clearance method). These predictions were then compared with observed concentration-time profiles at steady state. The mean difference between the observed values and those predicted from a morning test dose was -0.11 mumol l-1 (95% CI -7.0 to +7.2). A larger difference (-7.4 mumol l-1 95% CI -18.2 to +3.4) was found for the assumed clearance method. Since the confidence intervals contain zero, these differences are not significantly different from zero at the 5% level, although the morning test dose method allowed prediction of the whole concentration-time profile and was more precise. An evening test dose was also used in the study, but the mean difference between the observed values and those predicted from this method was larger at -24.8 mumol l-1 (95% CI -32.89 to -17.21) and was significantly different from zero. This study indicates that a morning test dose followed by a single blood sample can be used to establish maintenance theophylline therapy quickly and safely in selected patients.

Adult↗
PubMed1990

Stomach cancer and work in dusty industries.

The city of Stoke-on-Trent, whose major industries include coalmining, iron and steel, ceramics, and rubber, has death rates from stomach cancer some 80% above the national average. To explore the hypothesis that work in these dusty industries is responsible for the local excess of stomach cancer, we compared 95 incident cases with 190 age and sex matched community controls. Lifetime occupational histories and premorbid consumption of foods suspected of causing or protecting against stomach cancer were ascertained by a self administered questionnaire, supplemented at interview. Sixty eight cases had at some time held a manual job in one of the four dusty industries (relative risk = 1.4, 95% confidence interval 0.8-2.4). After allowance for diet, rubber manufacture was the industry most strongly associated with stomach cancer (relative risk = 2.5, 95% CI 1.0-6.4). Associations were also found with coal mining and ceramics but these were not statistically significant at a 5% level. The estimated proportion of stomach cancer attributable to the four dusty industries was 23%. It is concluded that the high incidence of stomach cancer in Stoke-on-Trent is unlikely to be explained solely by occupational exposure to dust.

Adult↗
PubMed1989

Stomach cancer and food storage.

To examine the influence of food storage habits on the development of stomach cancer, we compared 95 patients and 190 controls selected from the general population. Information about food storage and diet was obtained from the patients and the controls by use of a questionnaire mailed to each subject followed by an interview. Low intake of salad vegetables and fruit and high intake of salt were clearly associated with stomach cancer development. No association was found with recent refrigerator use, but a halving of stomach cancer risk in subjects who had used a refrigerator for greater than or equal to 29 years persisted after allowance was made for recent diet. Risk was elevated in subjects who, when children, had lived in houses without a larder built specifically for the storage of food.

Adult↗
PubMed1989

Respiratory tuberculosis in the potteries.

A comparison of the notification rates for pulmonary tuberculosis from 1930 onwards between England and Wales and Stoke-on-Trent County Borough shows an excess for Stoke-on-Trent which lasted until the 1950s. A comparison of mortality rates, however, reveals an excess in Stoke-on-Trent which has lasted until the present day. This excess mortality is attributed to a difference in the age distribution of pulmonary tuberculosis in England and Wales compared with Stoke-on-Trent, where there is a striking peak in the incidence of the disease in elderly men and women from the 1950s onwards. It is suggested that this peak is due to reactivation of pulmonary tuberculosis in the cohort who were born in the early years of this century and experienced a severe epidemic of tuberculosis in early adult life which was worse in Stoke-on-Trent than in England and Wales as a whole. The severity of the epidemic in the Potteries may have been attributable to poor environmental conditions including exposure to silica dust among workers in the ceramics industry.

Adult↗
PubMed1987

Surgical management of infants with complex cardiac anomalies associated with reduced pulmonary blood flow and total anomalous pulmonary venous drainage.

Eight infants with complex cardiac anomalies and pulmonary stenosis or atresia were noted to have obstructed total anomalous pulmonary venous drainage (TAPVD) either at the initial cardiac catheterization (Group 1; n = 2) or after creation of systemic-pulmonary artery shunts (Group 2; n = 6). The 2 patients in Group 1 underwent early repair of TAPVD (1 at 7 days, the other at 1 1/2 months of age) before any subsequent operation and are now doing well at 18 months of age. The 6 patients in Group 2 underwent repeat cardiac catheterization because of persistent severe cyanosis with faint or absent continuous murmur and were found to have patent shunts and obstructed TAPVD (1 mild, 5 severe). One patient who underwent repair of TAPVD at 2 1/2 months of age survived and is well at 2 years of age, whereas 4 patients who underwent repair at an average age of 6 months (age range, 3-16 months) subsequently died. The sixth patient, who did not undergo repair, remained severely cyanotic with hypoplastic pulmonary arteries in spite of repeated shunts. We feel that increased awareness of the possible association of TAPVD and reduced pulmonary blood flow in infants with complex cardiac defects, in combination with echocardiography, oxygen saturation studies, and angiography with prostaglandin E1 challenge, should lead to early diagnosis, avoidance of unnecessary systemic-pulmonary artery shunts, and increased survival rates in these infants.

Constriction, Pathologic↗
PubMed1984

The problems of tuberculosis in the elderly.

A prospective study of tuberculosis notifications from 1976 to 1980 in the North Staffordshire Health District (NSHD), an area with only a small immigrant population, has been carried out. The notification rate for all new cases of tuberculosis in white patients over 55 years of age in the NSHD was twice that reported for England and Wales by the Medical Research Council (1980). Of 433 cases in all ethnic groups 52 (12 per cent) were diagnosed only at necropsy. In addition 48 (11 per cent) died before treatment was completed. Tuberculosis was the only cause of death in 39 of these 100 cases and contributed to death in a further 19 cases, the site of disease being thoracic in 86. Of those who died before completion of treatment, tuberculosis was the cause of death or contributory in 23 and 16 of the 23 (70 per cent) had been on treatment for less than 13 weeks. Death occurred more commonly before or during treatment with increasing age. In a retrospective study of treatment during 1979 and 1980, major unwanted drug-induced effects occurred in 40 per cent of all treated cases in the over-65 age group, mostly related to rifampicin. The survey highlighted the problems of tuberculosis in the elderly white population. They present with advanced disease, are diagnosed late and their course is complicated by other disease and a poor tolerance of therapy.

Adolescent↗
PubMed1983

The role of the Glenn shunt in patients undergoing the Fontan operation.

Twenty-seven patients (3 to 22 years) underwent the Fontan operation. Seventeen had tricuspid atresia and 10 had other complex lesions. Sixteen patients had a Glenn shunt (12 prior to, three simultaneous with, and one following the Fontan operation). One early death (3.7%) occurred in a 4 1/2-year-old child with tricuspid atresia II-C, previous pulmonary artery banding, and a closing ventricular septal defect (80 mm Hg gradient). There were two late deaths (7.4%) from Candida sepsis, after 4 and 6 months, respectively. The 24 patients who survived the Fontan operation had postoperative hospital stays of 6 to 90 days (average 18). Patients with tricuspid atresia and an established Glenn shunt (nine patients, Group I) had postoperative hospital stays of 7 to 19 days (average 9.5), and none had significant pleural or pericardial effusions. Patients with tricuspid atresia without a Glenn shunt (seven patients, Group II) had postoperative hospital stays of 6 to 60 days (average 17.5), with three having significant effusions. Of the patients with other complex lesions, all without an established Glenn shunt, five had significant effusions. Four additional major complications (two tricuspid patch disruptions with ineffective pulmonary blood flow and two complete occlusions of a valved conduit) were encountered in which the Glenn shunt proved lifesaving. We believe that an established Glenn shunt played a major role in attaining minimal postoperative hemodynamic instability, effusions, renal failure, and mortality in our patients. The Glenn shunt should be considered in patients who are less than ideal candidates for the Fontan operation.

Adolescent↗