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Biomedical subjects

A Murray

Publications and source records attributed to A Murray.

At least 73 records · Page 4Linked to original sources

Direct isolation of monoclonal antibodies from tissue culture supernatant using the cation-exchange cellulose Express-Ion S.

The chromatography of the murine hybridoma cell C595/102 culture supernatant expressing the therapeutic monoclonal antibody C595, on the cation-exchange cellulose Whatman Express-Ion Exchanger S has been investigated. Initial method scouting studies using purified C595 in 1-ml mini columns demonstrated that binding capacity and binding efficiency were dependent not only on decreasing pH but also on the buffer salts used to prepare the mobile phase. Under optimised conditions of 0.1 M sodium acetate buffer, pH 5.0, we were able to separate purified C595 from BSA, the major contaminant in tissue culture fluid. Under these conditions immunoreactive C595 could be isolated directly from tissue culture supernatant. A scale-down study was carried out using a 25-ml column operated at a flow-rate of 150 cm/h which also yielded purified immunoreactive antibody. This procedure should now be suitable for scale-up.

Animals↗

Haplotypic determinants of instability in the FRAX region: Concatenated mutation or founder effect?

The fragile X triplet repeat expansion at Xq27.3 has been shown to be associated with mutation or instability 600 kb distal at the FMR2 repeat locus. Concatenated mutation, whereby a mutation at one locus somehow interacts with mutation, recombination, deletion, or transposition at another locus, is a possible explanation. In this study we examine evidence from a sample of over 7,000 independent haplotypes from the FRAX region. We adopt the use of cladistic groups to more thoroughly define the properties of these haplotypes, and in doing so isolate one group of haplotypes which may be predisposed to the phenomenon of concatenated mutation. Distinguishing concatenated mutation from founder effects is difficult within a single population. We present our evidence for and against concatenated mutation, and in the process describe a previously undefined mutation at FRAXE.

Alleles↗

Comparative detection of measles and rubella IgM and IgG derived from filter paper blood and serum samples.

We compared the use of serum and filter paper blood spots as specimen sources for the detection of measles- and rubella-specific IgM and IgG. We collected capillary blood into microtainer tubes and onto filter paper spots from 60 children and 60 healthy adults. The blood was collected from 12-15-month-old children approximately 3 weeks after primary vaccination with measles, mumps, rubella vaccine, and the sample-pairs were tested for measles-specific IgM and IgG antibodies by using a capture antibody EIA and an indirect EIA, respectively. We tested sample-pairs from a subset of participants for rubella- specific IgM and IgG antibodies by using commercially available capture IgM (Captia) and indirect IgG (Wampole) assays. The concordance of results from serum and filter paper blood spots was high for all assays: 98% for measles IgM, 93% for measles IgG, 94% for rubella IgM, and 93% for rubella IgG, and increased to between 96-100% for all four assays when indeterminate samples were excluded. The correlation coefficients for EIA signals were 0.99 and 0.77 for measles IgM and IgG, respectively, and 0.92 and 0.94 for rubella IgM and IgG, respectively. The cut-off values used for filter paper samples were the same as those used for serum samples for all tests except for the rubella IgM assay. The use of filter paper blood spots is a promising future option for the detection of measles- and rubella-specific antibodies.

Adult↗

Production and characterisation of a C595 antibody-99mTc conjugate for immunoscintigraphy of bladder cancer.

Current radiological techniques for staging bladder cancer are inaccurate, especially in the identification of pelvic lymph node metastases. Immunoscintigraphy has the potential to offer improved staging for bladder cancer. The aim of this study was to label the anti-MUC1 monoclonal antibody C595 with 99mtechnetium (Tc), the most widely used diagnostic radionuclide, and assess the potential of the resultant conjugate for intravenous immunoscintigraphy of bladder cancer. A direct, reduction-mediated technique was used to label the antibody. The resultant conjugate was shown to be highly immunoreactive, stable and bound specifically to MUC1. The ability of the conjugate to bind to bladder tumours was demonstrated in an ex vivo model where the mean tumour:normal urothelial uptake was 5.7:1 and by intravesical administration in patients with bladder cancer where the mean tumour:normal urothelial uptake was 20.4:1. The ability of the conjugate to localise MUC1-expressing tumours was demonstrated in a nude mouse xenograft model. A conjugate of 99mTc-C595 has been produced and characterised, and it may be suitable for intravenous immunoscintigraphy, a potential novel staging tool for bladder cancer.

Animals↗

Molecular and phylogenetic characterisation of Cryptosporidium from birds.

Avian isolates of Cryptosporidium species from different geographic locations were sequenced at two loci, the 18S rRNA gene and the heat shock gene (HSP-70). Phylogenetic analysis of the sequence data provided support for the existence of a new avian species of Cryptosporidium infecting finches and a second species infecting a black duck. The identity of Cryptosporidium baileyi and Cryptosporidium meleagridis as valid species was confirmed. Also, C. baileyi was identified in a number of isolates from the brown quail extending the host range of this species.

Animals↗

Using benthic recruitment to assess the significance of contaminated sediments: the influence of taxonomic resolution.

The use of small-scale experimental units as a means of evaluating the ecological effects of contaminated sediments was examined at the species, family, mixed and phylum levels of taxonomic resolution. Sediments were taken from various locations representing a range of contaminant loads. Containers with these sediments were placed in situ at a relatively uncontaminated location for 90 days. The containers were retrieved and the abundance of the macrofauna which recruited to the containers was estimated. The results showed that the composition of the benthic communities in the more highly contaminated sediments differed significantly from those in less contaminated sediments. Analyses at the different taxonomic levels showed that all but the phylum level data showed some differences in community structure among sediment types. The study showed that small-scale experiments are useful for examining the effects of contaminants and that higher levels of taxonomic resolution can be used to describe variations in the structure of benthic communities at this spatial scale.

Animals↗

Switching from Ventolin CFC to Ventolin HFA is well tolerated and effective in patients with asthma.

BACKGROUND: Environmental imperatives to eliminate the use of chlorofluorocarbon (CFC) propellants in metered-dose inhalers have led to the development of metered-dose inhalers with the hydrofluoroalkane (HFA-134a) propellants. OBJECTIVES: To evaluate the clinical effect of switching from Ventolin CFC to Ventolin HFA and to compare the efficacy and safety of Ventolin CFC, Ventolin HFA, and placebo in patients with asthma. METHODS: Multicenter, double-blind, randomized safety and efficacy trial comparing regular use of Ventolin CFC versus Ventolin HFA versus placebo for 12 weeks in 313 patients with asthma aged 12 years and older who received Ventolin CFC during a 3-week run-in period. RESULTS: Patients who were switched from Ventolin CFC to Ventolin HFA maintained pulmonary function and other measures of asthma control at levels comparable with run-in baseline. Serial pulmonary function testing demonstrated that both Ventolin treatments had significantly greater mean improvement in FEV1 over baseline than the placebo group at treatment day 1 and weeks 6 and 12 (P < .001). Both Ventolin groups had comparable pulmonary function at every visit. Predose FEV1 values were maintained or improved over time with all treatments. Treatments were well-tolerated. The adverse event profile for both Ventolin treatments was comparable with placebo. No clinically relevant effects on ECG, vital signs, or clinical laboratory tests were noted. Asthma exacerbation rates were 4% to 5% in the Ventolin groups and slightly higher (8%) in the placebo group. CONCLUSIONS: Patients who were switched from Ventolin CFC to Ventolin HFA maintained comparable asthma control with a similar safety profile.

Adolescent↗

Distribution of FMR1 and FMR2 alleles in Javanese individuals with developmental disability and confirmation of a specific AGG-interruption pattern in Asian populations.

The number of trinucleotide repeats in the 5' untranslated regions of the FMR1 and FMR2 genes was determined by PCR in 254 Fragile XA-negative Javanese male children with developmental disabilities. The distribution of FMR1 and FMR2 trinucleotide repeat alleles was found to be significantly different in the Indonesian population with developmental disability compared to that in developmentally disabled populations in North America and Europe (p & 0.021). Sequence analysis was performed on the trinucleotide repeat arrays of the 27 individuals with FMR1 alleles in the 'grey zone' (35-54 repeats). A repeat array structure of 9A9A6A9 was found in 16 unrelated individuals with 36 repeats, confirming earlier observations in intellectually normal Japanese. We propose that this FMR1 array pattern is specific for Asian populations and that Javanese and Japanese populations arose from a single progenitor population.

Alleles↗

Double primary cancers of the breast and thyroid in women: molecular analysis and genetic implications.

Multiple primary cancers are characteristic of hereditary cancer syndromes. A familial association between breast and thyroid cancer has been suggested, but a genetic basis for this association has not yet been established. To determine the extent to which double primary cancers of the breast and thyroid are due to common hereditary factors, we conducted a registry- and hospital-based study in Ontario and Quebec. We obtained family histories of 74 women diagnosed with both cancer of the breast and thyroid before 70 years of age. Cancer histories were obtained for the 533 first- degree relatives of these women. The observed cancer rate in the relatives was compared with the expected number, based on age- standardized Canadian cancer incidence rates, and relative risks were estimated. A total of 87 cancers were observed in the relatives, compared to 93.7 expected cancers, giving a relative risk of 0.9 (95% confidence interval (CI): 0.7-1.1). The risk for breast cancer was 1.1 (95% CI: 0.6-1.7) and the risk for thyroid cancer was 0.7 (95% CI: 0-3.8). Blood samples were collected on 53 patients for mutational analysis of the BRCA1, BRCA2, and PTEN genes. One woman was found to be a carrier of a BRCA1 mutation (exon 11 3227delT). Our findings do not support the hypothesis that a significant proportion of double primary cancers of the breast and thyroid are due to hereditary factors.

Adult↗

Balloon dacryocystoplasty study in the management of adult epiphora.

PURPOSE: To determine the efficacy of dacryocystoplasty with balloon dilation in the treatment of acquired obstruction of the nasolacrimal system in adults. METHODS: Balloon dacryocystoplasty was performed in 52 eyes of 42 patients under general anaesthetic. A Teflon-coated guidewire was introduced through the canaliculus and manipulated through the nasolacrimal system and out of the nasal aperture. A 4 mm wide 3 cm coronary angioplasty balloon catheter was threaded over the guidewire in a retrograde fashion and dilated at the site of obstruction. RESULTS: There was complete obstruction in 30% of cases and partial obstruction in 70%. The most common site of obstruction was the nasolacrimal duct. The procedure was technically successful in 94% of cases. The overall re-obstruction rate was 29% within 1 year of the procedure. There was an anatomical failure rate of 17% for partial obstruction and 69% for complete obstruction within 1 year. CONCLUSIONS: Balloon dacryocystoplasty has a high recurrence rate. There may be a limited role for this procedure in partial obstructions. Further refinements of the procedure are necessary before it can be offered as a comparable alternative to a standard surgical dacryocystorhinostomy.

Adolescent↗

A clinical study of the Korotkoff phases of blood pressure in children.

BACKGROUND: Five Korotkoff phases are described in adults, but there are no studies of the Korotkoff phase distribution in children. This study determines the presence and length of Korotkoff phases in children, providing data on the repeatability of these measurements, the relationship between the phases, and finally the relationship between the phases and heart rate, blood pressure and arm circumference. METHODS: Seventy, 11-year-old children were studied. The Korotkoff sounds were recorded from the bell of a stethoscope to a MiniDisc system and each sound described twice on separate occasions as phase I, II, III or IV, with phase V meaning disappearance of the sound. RESULTS: Phases I, II, III, IV and V were present in 97% (68/70), 61% (43/70), 51% (36/70), 88% (62/70) and 80% (56/70) respectively. When the recordings were blindly re-assessed there was no significant difference in the phase distribution of the sounds. All five phases were present in 40% (28/70). Phase III only occurred in the presence of phase II (P < 0.0001). There was no significant relationship between the presence of the different phases and heart rate or blood pressure. Arm circumference was significantly larger in children with phase V present (P < 0.02). CONCLUSIONS: The Korotkoff sounds and phase distribution present in normal children is described. Korotkoff sounds were consistently allocated to the various Korotkoff phases. This study provides insights into the problems of accurate diastolic blood pressure measurement. Phase V was more likely to be present with increasing arm circumference, but the variation in the occurrence of phases II and III remains unexplained.

Arm↗

Effect of lead exclusion for the manual measurement of QT dispersion.

To investigate the effect of different lead exclusion criteria for the manual measurement of QT dispersion (QTd). Simultaneous 12-lead ECGs from three groups of 25 subjects were studied; healthy normal subjects, subjects with a myocardial infarction, and subjects with arrhythmias. Leads were excluded with (1) small absolute T wave amplitudes, (2) small relative T wave amplitudes, and (3) small and/or large relative QT measurements. QTd was calculated as the QT range and assessed for its ability to differentiate between the normal and pathological groups. With exclusion of no leads or low absolute amplitude T waves (< 50 microV) significant differences were observed only between normal and myocardial infarct groups (P < 0.05). Significant differences between normal and both pathological groups were observed when excluding the lead with the smallest amplitude T wave or shortest QT (P < 0.05), or when two leads of either type were excluded (P < 0.005). There was good agreement between leads excluded by amplitude or QT (P < 0.01). Lead exclusion for QTd is important. Exclusion of the two smallest amplitude or two shortest QT leads from each subject produced the greatest differences between the normal and pathological groups.

Arrhythmias, Cardiac↗

Doctor discontent. A comparison of physician satisfaction in different delivery system settings, 1986 and 1997.

OBJECTIVE: To examine the differences in physician satisfaction associated with open- versus closed-model practice settings and to evaluate changes in physician satisfaction between 1986 and 1997. Open-model practices refer to those in which physicians accept patients from multiple health plans and insurers (i.e., do not have an exclusive arrangement with any single health plan). Closed-model practices refer to those wherein physicians have an exclusive relationship with a single health plan (i.e., staff- or group-model HMO). DESIGN: Two cross-sectional surveys of physicians; one conducted in 1986 (Medical Outcomes Study) and one conducted in 1997 (Study of Primary Care Performance in Massachusetts). SETTING: Primary care practices in Massachusetts. PARTICIPANTS: General internists and family practitioners in Massachusetts. MEASUREMENTS: Seven measures of physician satisfaction, including satisfaction with quality of care, the potential to achieve professional goals, time spent with individual patients, total earnings from practice, degree of personal autonomy, leisure time, and incentives for high quality. RESULTS: Physicians in open- versus closed-model practices differed significantly in several aspects of their professional satisfaction. In 1997, open-model physicians were less satisfied than closed-model physicians with their total earnings, leisure time, and incentives for high quality. Open-model physicians reported significantly more difficulty with authorization procedures and reported more denials for care. Overall, physicians in 1997 were less satisfied in every aspect of their professional life than 1986 physicians. Differences were significant in three areas: time spent with individual patients, autonomy, and leisure time (P < or =.05). Among open-model physicians, satisfaction with autonomy and time with individual patients were significantly lower in 1997 than 1986 (P < or =.01). Among closed-model physicians, satisfaction with total earnings and with potential to achieve professional goals were significantly lower in 1997 than in 1986 (P < or =.01). CONCLUSIONS: This study finds that the state of physician satisfaction in Massachusetts is extremely low, with the majority of physicians dissatisfied with the amount of time they have with individual patients, their leisure time, and their incentives for high quality. Satisfaction with most areas of practice declined significantly between 1986 and 1997. Open-model physicians were less satisfied than closed-model physicians in most aspects of practices.

Adult↗

Assessment of computer-controlled inflation/deflation for determining the properties of PTCA balloon catheters with pressure-volume curves.

Restenosis is a significant problem after percutaneous transluminal coronary angioplasty (PTCA), leading to further angina or even death. The mechanisms causing restenosis are not well understood and the effect of the angioplasty balloon on the artery wall is generally unknown. The aim of the research presented here was to assess the repeatability with which measurements of balloon pressure-volume characteristics could be made, to ensure that different balloons could be distinguished easily, an essential first step before the arteries themselves could be characterized. An inflation/deflation device was inflated with and without an attached balloon under computer control at a constant speed to 8 bar. The accuracy and repeatability of the technique was assessed within a single measurement session and between measurement sessions on six separate days. For each measurement session, four repeated inflations/deflations were carried out and the average was determined. Compliance (volume change/pressure change), inflation volume and pressure drop at 8 bar were determined for various balloon catheters of different size, type and manufacturer. The system repeatability SD for measuring volume without a balloon was +/- 0.0005 ml within a single measurement session, and +/- 0.002 ml between independent days. With an attached balloon the repeatability SD for measuring volume was +/- 0.001 ml within, and +/- 0.003 ml between days. Compliance was determined with a repeatability SD of +/- 0.16 microliter bar-1 within, and +/- 0.94 microliter bar-1 between days. The inflation/deflation device and technique employed allowed small changes in volume and compliance to be differentiated. The system also enabled differences due to the material characteristics for different PTCA balloons to be determined. Measured balloon characteristics were similar to the data given by manufacturers. This gives confidence in development of the technique for clinical use.

Air Pressure↗

Relation between heart rate and pulse transit time during paced respiration.

Pulse transit time (PTT) is a simple, non-invasive measurement, defined as the time taken from a reference time for the pulse pressure wave to travel to the periphery. PTT is influenced by heart rate, blood pressure changes and the compliance of the arteries, but few quantitative data are available describing the factors which influence PTT. The aim of this study was to investigate the relationship between the cardiac beat-to-beat interval (RR) and PTT, using paced respiration to generate changes in both variables. We analysed PTT and RR interval from 15 normal healthy subjects during paced breathing, and the cross-correlation function between PTT and RR was used to quantify their relationship. Over the 15 subjects, the maximum change in PTT ranged from 7 to 23 ms with a mean +/- standard deviation of 14 +/- 5 ms, and that in RR interval from 86 to 443 ms (241 +/- 102 ms). Examining changes over time, the best correlation (r = +0.69, p < 0.01) was obtained when PTT was advanced relative to RR, with a change in RR followed by a corresponding change in PTT 3.17 +/- 0.76 beats later. We conclude that there is a strong relationship between PTT changes and RR interval changes, but these changes are not in phase.

Adult↗

Digital photography in orthodontics.

A brief history of digital photography is provided along with a critical appraisal of the 'prosumer' and professional systems currently available. Recommendations are made as to the system best suited to current orthodontic practice.

Humans↗

Evaluation of the Mycobacterium bovis restriction fragment length polymorphism probe pUCD, in combination with the direct repeat probe, for molecular typing of Mycobacterium tuberculosis strains in Ireland.

A mycobacterial restriction fragment length polymorphism probe, pUCD, has recently been described which represents an effective tool for the strain typing of Mycobacterium bovis. The present study evaluated this probe, in combination with the direct repeat probe (DR), for the molecular typing of 90 strains of Mycobacterium tuberculosis from 87 patients, looking at a group (62 isolates) of nonselected samples to assess pUCD combined with DR as a general tool and a subset of 32 isolates with a common specific IS6110 strain type in Ireland. Within the group of 62 isolates, pUCD-DR identified 42 strains and was comparable to both IS6110 (41 strains) and polymorphic guanine-cytosine-rich sequence (PGRS) (37 strains) analysis. pUCD-DR was found to be comparable to IS6110 and PGRS in identifying four separate clusters of isolates which were confirmed to be clinically related. pUCD-DR divided the common IS6110 isolates into six distinct types and was comparable to PGRS (seven strain types). The usefulness of this probe as an epidemiological tool is discussed.

Bacterial Typing Techniques↗