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Biomedical subjects

R Jones

Publications and source records attributed to R Jones.

At least 235 records · Page 13Linked to original sources
PubMed1999

Likely impacts of recruitment site and methodology on characteristics of enrolled patient population: irritable bowel syndrome clinical trial design.

Approximately 15-20% of the general population of many western countries fulfill clinical diagnostic criteria for irritable bowel syndrome (IBS) and nearly 50% of referrals and follow-up appointments in hospital gastroenterology clinics are for functional bowel disorders. IBS is a common problem in the community, in primary care (general practice) and in secondary care (hospital, usually ambulatory) settings, and is also seen in tertiary (referral) centers, providing at least four potential settings for recruitment of patients into clinical trials. However, little is known about the influences that cause patients to choose different health-care settings or to stay away from the health-care system as "nonconsulters." Also, it is not known if patients seen at different health-care settings differ from each other. The aim of this review is to address the following questions: To what extent do subjects identified and enrolled in these settings differ from each other? What is the likely impact of different recruitment methods on subject selection? What problems for the interpretation and generalizability of data from clinical trials might these differences pose? What is the role of the sociomedical context (cultural beliefs and values and the structure of the health-care system) in different countries on the interpretation of clinical studies?

Clinical Trials as Topic↗
PubMed1999

Randomised trial of personalised computer based information for cancer patients.

OBJECTIVE: To compare the use and effect of a computer based information system for cancer patients that is personalised using each patient's medical record with a system providing only general information and with information provided in booklets. DESIGN: Randomised trial with three groups. Data collected at start of radiotherapy, one week later (when information provided), three weeks later, and three months later. PARTICIPANTS: 525 patients started radical radiotherapy; 438 completed follow up. INTERVENTIONS: Two groups were offered information via computer (personalised or general information, or both) with open access to computer thereafter; the third group was offered a selection of information booklets. OUTCOMES: Patients' views and preferences, use of computer and information, and psychological status; doctors' perceptions; cost of interventions. RESULTS: More patients offered the personalised information said that they had learnt something new, thought the information was relevant, used the computer again, and showed their computer printouts to others. There were no major differences in doctors' perceptions of patients. More of the general computer group were anxious at three months. With an electronic patient record system, in the long run the personalised information system would cost no more than the general system. Full access to booklets cost twice as much as the general system. CONCLUSIONS: Patients preferred computer systems that provided information from their medical records to systems that just provided general information. This has implications for the design and implementation of electronic patient record systems and reliance on general sources of patient information.

Attitude to Computers↗
PubMed1999

Dose-response effects of 32P radioactive stents in an atherosclerotic porcine coronary model.

BACKGROUND: Experimental studies have demonstrated that 32P radioactive stents reduce neointimal formation at 28 days in porcine iliac and coronary arteries. Our objective was to determine the long-term dose-response effects of 1.0- to 12.0-microCi 32P radioactive stents in a porcine atherosclerotic coronary model. METHODS AND RESULTS: Control (n=19) and 1.0- to 12.0-microCi 32P radioactive (n=43) stents (total, n=62) were implanted in the coronary arteries of 31 miniature swine at 28 days after creation of a fibrocellular plaque by overstretch balloon injury and cholesterol feeding. Angiography and histomorphometry were performed at 6 months. Stent thrombosis occurred in 3 radioactive (7.7%) and no control stents (P=0.54). On histology, the mean neointimal area and the percent in-stent stenosis correlated positively with increasing stent activity (r=0.64, P<0.001). The mean neointimal area (mm2) for the stents with >/=3.0 microCi 32P (3.57+/-1.21) was significantly greater than that for the nonradioactive stents (1.78+/-0.68, P<0.0001). The neointima of the stents with >/=3.0 microCi 32P was composed of smooth muscle cells, matrix proteoglycans, calcification, foam cells, and cholesterol clefts. CONCLUSIONS: Continuous low-dose-rate irradiation delivered by high-activity (32)P radioactive stents promotes the formation of an "atheromatous" neointima after 6 months in this experimental model. These data may be useful for predicting late tissue responses to radioactive stents in human coronary arteries.

Animals↗
PubMed1999

Prescribing. Short rations.

A national survey of old-age psychiatrists showed patchy and generally low prescribing of the Alzheimer's drug Donepezil. Most health authorities had 10 patients, or fewer, on the drug last year. The ethics of the present position should be examined by a third party.

Aged↗
PubMed1999

Rapid structural characterisation of a murine monoclonal IgA alpha chain: heterogeneity in the oligosaccharide structures at a specific site in samples produced in different bioreactor systems.

A murine hybridoma cell line which secretes a monoclonal IgA antibody, directed against the LPS antigen of Vibrio cholerae, was grown in either a continuous stirred tank reactor, a fluidised bed reactor or a hollow fibre reactor. Different methods were used for the structural characterisation of the IgA alpha chains. A classical approach consisted of Edman sequencing and mass determination of peptides separated by reversed phase HPLC. Alternatively, peptides and glycopeptides from a tryptic digest of each alpha chain were identified directly by MALDI-TOF mass spectrometry. A detailed analysis of the oligosaccharide structures at an unique site on the alpha chain was made by labelling the oligosaccharides released by N-glycosidase F with 1-(p-methoxy)phenyl-3-methyl-5-pyrazolone. After separation by HPLC, mass measurements were made using matrix-assisted laser desorption time of flight mass spectrometry before and after digestion with specific exoglycosidases. The primary structure of the alpha chain of IgA was not affected by different cell culture conditions; in contrast, significant variations could be detected in the pattern of N-linked oligosaccharide structures, most prominently in the degree of sialylation. The efficiency of the analytical techniques in providing quality control of the identity, integrity and consistency of the glycoprotein is shown and discussed.

Amino Acid Sequence↗
PubMed1999

A randomized phase 3 study of peripheral blood progenitor cell mobilization with stem cell factor and filgrastim in high-risk breast cancer patients.

This randomized study compared the number of leukaphereses required to collect an optimal target yield of 5 x 10(6) CD34(+) peripheral blood progenitor cells/kg, using either stem cell factor (SCF) at 20 micrograms/kg/d in combination with Filgrastim at 10 micrograms/kg/d or Filgrastim alone at 10 micrograms/kg/d, from 203 patients with high-risk stage II, III, or IV breast cancer. Leukapheresis began on day 5 of cytokine administration and continued daily until the target yield of CD34(+) cells had been reached or a maximum of 5 leukaphereses performed. By day 5 of leukapheresis, 63% of the patients treated with SCF plus Filgrastim (n = 100) compared with 47% of those receiving Filgrastim alone (n = 103) reached the CD34(+) cell target yield. There was a clinically and statistically significant reduction (P <.05) in the number of leukaphereses required to reach the target yield for the patients receiving SCF plus Filgrastim (median, 4 leukaphereses) compared with patients receiving Filgrastim alone (median, 6 or more leukapherses; ie, <50% of patients reached the target in 5 leukaphereses). All patients receiving SCF were premedicated with antihistamines, albuterol, and pseudoephedrine. Treatment was safe, generally well tolerated, and not associated with life-threatening or fatal toxicity. In conclusion, SCF plus Filgrastim is a more effective peripheral blood progenitor cell (PBPC)-mobilization regimen than Filgrastim alone. In addition to the potential for reduced leukapheresis-related morbidity and costs, SCF offers additional options for obtaining cells for further graft manipulation.

Adult↗
PubMed1999

Nuclear and neuropil aggregates in Huntington's disease: relationship to neuropathology.

The data we report in this study concern the types, location, numbers, forms, and composition of microscopic huntingtin aggregates in brain tissues from humans with different grades of Huntington's disease (HD). We have developed a fusion protein antibody against the first 256 amino acids that preferentially recognizes aggregated huntingtin and labels many more aggregates in neuronal nuclei, perikarya, and processes in human brain than have been described previously. Using this antibody and human brain tissue ranging from presymptomatic to grade 4, we have compared the numbers and locations of nuclear and neuropil aggregates with the known patterns of neuronal death in HD. We show that neuropil aggregates are much more common than nuclear aggregates and can be present in large numbers before the onset of clinical symptoms. There are also many more aggregates in cortex than in striatum, where they are actually uncommon. Although the striatum is the most affected region in HD, only 1-4% of striatal neurons in all grades of HD have nuclear aggregates. Neuropil aggregates, which we have identified by electron microscopy to occur in dendrites and dendritic spines, could play a role in the known dendritic pathology that occurs in HD. Aggregates increase in size in advanced grades, suggesting that they may persist in neurons that are more likely to survive. Ubiquitination is apparent in only a subset of aggregates, suggesting that ubiquitin-mediated proteolysis of aggregates may be late or variable.

Amino Acid Sequence↗
PubMed1999

The effect of smoking in pregnancy on maternal serum inhibin A levels.

To assess the effect of smoking on maternal serum, second-trimester inhibin A levels, we studied a database of 1277 women undergoing antenatal serum screening. There were 75 smokers, 1008 non-smokers and 194 women in whom smoking status was undetermined. All groups were matched for age, gestation and parity. The median level of inhibin A in smokers was 1.47 multiples of the normal gestation-specific median (MOM) as compared with 1.01 MOM in non-smokers and 0.95 MOM in the undetermined group. The increase was highly statistically significant (p<0.0001, Wilcoxon rank sum test, two-tail). On the basis of these results we conclude that if inhibin A is used as a marker, adjustment for maternal smoking status may be necessary.

Adult↗
PubMed1999

Structural elucidation studies of erythromycins by electrospray tandem mass spectrometry.

Erythromycin A (EryA) was studied by electrospray ionisation tandem mass spectrometry (ESI-MS/MS) with the aim of developing a methodology for the structural elucidation of novel erythromycins developed by biological synthetic methods. Skimmer dissociation along with sequential mass spectrometry studies (up to MS5) have been employed in this study. In the low-resolution MS/MS analysis of the polyketides, there are several fragment ions that are easily assigned to various neutral losses. These have all been confirmed by accurate-mass measurements. There is also a series of peaks due to ring opening and fragmentation that can only be assigned by high-resolution MSn analysis. Further experiments were performed in deuterated media (D2O/CD3OD 50%) which, along with the high-resolution MSn of erythromycin analogues, has enabled us to identify some of the steps in the ring fragmentation, particularly the loss of the polyketide starter acid. This is an essential step for determining structural alterations in the novel polyketides, but further labelling experiments and studies on more erythromycin analogues are required before the complete fragmentation pathway can be confirmed.

Anti-Bacterial Agents↗
PubMed1999

Structural elucidation studies of erythromycins by electrospray tandem mass spectrometry II.

Erythromycin A (EryA), sec-butyl erythromycin B (SEryB), oleandomycin (Olean) and a synthetic derivative, roxithromycin (Rox), were used to investigate the fragmentation of polyketide macrolide antibiotics by collision induced dissociation (CID) tandem mass spectrometry (MS/MS). Analyses were performed with two commercially available mass spectrometers: a Q-TOF hybrid quadrupole time-of-flight instrument and a BioApex II (4.7 Tesla) Fourier transform ion cyclotron resonance (FTICR) instrument both equipped with electrospray ionisation (ESI) sources. One of the first fragmentation processes is the loss of an H(2)O molecule from the [M+H](+) ion. EryA has three hydroxyl groups on the polyketide ring and loses three H(2)O molecules during CID. This study indicates that these facts are not necessarily related. Deuterium exchange experiments were carried out in order to isotopically label free hydroxyl groups. (18)O-exchange experiments were also carried out in order to label the carbonyl group at the 9-position. In EryA and its analogue the first H(2)O loss shifts in mass from loss of 18 Da to loss of 20 Da in deuterated solvents. For both molecules the loss also shifts in mass from loss of 18 Da to loss of 20 Da during the (18)O-exchange experiments. This suggests that the first loss of H(2)O is from the 9-position carbonyl group, indicating that this, and not the nitrogen of the amino sugar, is the site of protonation of the activated MH(+) ions. For Rox the initial loss of H(2)O is replaced by loss of the 9-position oxime group, the rest of the fragmentation sequence being the same as for EryA. For Olean, there is no H(2)O loss from the parent ion. The results have allowed the proposal of a mechanism for the first loss of H(2)O in the EryA MS/MS fragmentation.

Anti-Bacterial Agents↗
PubMed1999

Lipid diffusion in the plasma membrane of ram and boar spermatozoa during maturation in the epididymis measured by fluorescence recovery after photobleaching.

Maturation of spermatozoa in the epididymis involves remodelling of many protein and lipid components of the plasma membrane. In this investigation we have examined whether (a) diffusion of lipid molecules in the surface membrane changes during epididymal maturation; (b) diffusion is spatially restricted; and (c) differences in lipid diffusion can be related to known changes in membrane composition. For this purpose we have used the technique of fluorescence recovery after photobleaching (FRAP) to measure diffusion of the lipid reporter probe ODAF (5-(octa-decanoyl)aminofluorescein) in spermatozoa from two species: ram, where substantial changes in membrane lipids occur during passage through the epididymis, and boar, where there are relatively few changes. Results on ram spermatozoa show that between the testis and cauda epididymidis, diffusion coefficients values (D) for ODAF increase significantly in all the surface domains. Percentage recovery values (%R) remain constant irrespective of maturational status. In boar spermatozoa, however, D and %R values do not change significantly between epididymal regions. Cholesterol, which has widespread effects on the behaviour of lipid molecules in cell membranes, was visualized by binding of filipin. In both species filipin was concentrated over the acrosomal domain and cytoplasmic droplet of testicular spermatozoa, but in the epididymis it had a heterogenous distribution over the whole head and tail. These results are discussed in relation to the establishment and maintenance of lipid domains in spermatozoa and their influence on development of fertilizing capacity.

Animals↗