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Biomedical subjects

P Miller

Publications and source records attributed to P Miller.

At least 55 records · Page 3Linked to original sources
PubMed2001

Neurodevelopmental indices and the development of psychotic symptoms in subjects at high risk of schizophrenia.

BACKGROUND: Neurological 'soft signs' and minor physical anomalies (MPAs) are reported to be more frequent in patients with schizophrenia than in controls. AIMS: To determine whether these disturbances are genetically mediated, and whether they are central to the genesis of symptoms or epiphenomena. METHOD: We obtained ratings in 152 individuals who were antipsychotic drug-free and at high risk, some of whom had experienced psychotic symptoms, as well as 30 first-episode patients and 35 healthy subjects. RESULTS: MPAs and Neurological Evaluation Scale (NES) 'sensory integration abnormalities' were more frequent in high-risk subjects than in healthy controls, but there were no reliable differences between high-risk subjects with and without psychotic symptoms. MPAs were most frequent in high-risk subjects with least genetic liability and NES scores showed no genetic associations. CONCLUSIONS: The lack of associations with psychotic symptoms and genetic liability to schizophrenia suggests that soft signs and physical anomalies are nonspecific markers of developmental deviance that are not mediated by the gene(s) for schizophrenia.

Abnormalities, Multiple↗
PubMed2001

Importance of precision in bone density measurements.

Bone densitometry, regardless of the specific technique, is not perfectly reproducible even when consistently performed in exact accordance with the manufacturer's recommendations. Precision must be quantified at each densitometry facility in precision studies of the various skeletal sites used for monitoring. The precision, as the root-mean-square standard deviation or root-mean-square coefficient of variation, is then used to determine the change in bone density that constitutes the least significant change and the minimum interval between follow-up measurements. Until precision studies are performed, the least significant change cannot be determined for any level of statistical confidence, making the interpretation of serial studies impossible.

Absorptiometry, Photon↗
PubMed2001

Excretion of sweat and urine pyridinoline crosslinks in healthy controls and subjects with established metabolic bone disease.

Convenient techniques for measuring rates of bone turnover have been developed in recent years with the advent of biochemical markers of bone metabolism. One recent of these techniques is a collection method and quantitative enzyme immunoassay for free pyridinoline crosslinks in human sweat. The concentrations of pyridinoline crosslinks in 5-day sweat collections and first morning void and 24-hour urine collections from healthy subjects and subjects with established metabolic bone disorders were determined. T-scores were higher in the sweat system than in the urine system by up to 10-fold in postmenopausal subjects, women with hyperparathyroidism, and subjects with postmenopausal osteoporosis. For subjects with postmenopausal osteoporosis, receiver-operating characteristic curve analysis yielded areas under the curve of 0.699, 0.629, and 0.520 for sweat pyridinoline, first morning void urine pyridinoline, and 24 hour urine pyridinoline respectively. The areas under the curve of the sweat and first morning void urine measurements were significantly greater (p<0.05) than the 24-hour pyridinoline measurements. Healthy postmenopausal subjects and subjects with postmenopausal osteoporosis were monitored before and during estrogen replacement therapy or alendronate therapy. Sweat pyridinoline values declined by 49.0 +/- 12.4% and 19.4 +/- 19.9% for estrogen and alendronate subjects respectively. We conclude that this non-invasive technique is a sensitive and specific measure of bone resorption and is appropriate as an adjunct to techniques such as bone density and may also be useful in monitoring of response to anti-resorptive therapies.

Adult↗
PubMed2001

Stage Ia endometrial carcinoma diagnosed on removal of an IUD.

This is a case report of a 49-year-old woman who presented with offensive vaginal discharge. Her Lippes loop IUD was removed and discovered to have suspicious material attached. Histology report was of endometrial carcinoma. This is the first report of an endometrial carcinoma being completely removed along with an IUD.

Device Removal↗
PubMed2001

The role of radiography in primary care patients with low back pain of at least 6 weeks duration: a randomised (unblinded) controlled trial.

OBJECTIVES: To test the hypotheses that: (1) Lumbar spine radiography in primary care patients with low back pain is not associated with improved patient outcomes, including pain, disability, health status, sickness absence, reassurance, and patient satisfaction or belief in the value of radiography. (2) Lumbar spine radiography in primary care patients with low back pain is not associated with changes in patient management, including medication use, and the use of primary and secondary care services, physical therapies and complementary therapies. (3) Participants choosing their treatment group (i.e. radiography or no radiography) do not have better outcomes than those randomised to a treatment group. (4) Lumbar spine radiography is not cost-effective compared with usual care without lumbar spine radiography. DESIGN: A randomised unblinded controlled trial. SETTING: Seventy-three general practices in Nottingham, North Nottinghamshire, Southern Derbyshire, North Lincolnshire and North Leicestershire. Fifty-two practices recruited participants to the trial. SUBJECTS: Randomised arm: 421 participants with low back pain, with median duration of 10 weeks. Patient preference arm: 55 participants with low back pain, with median duration of 11 weeks. INTERVENTION: Lumbar spine radiography and usual care versus usual care without radiography. MAIN OUTCOME MEASURES: Roland adaptation of the Sickness Impact Profile, visual analogue pain scale, health status scale, EuroQol, use of primary and secondary care services, and physical and complementary therapies, sickness absence, medication use, patient satisfaction, reassurance and belief in value of radiography at 3 and 9 months post-randomisation. RESULTS: Participants randomised to receive an X-ray were more likely to report low back pain at 3 months (odds ratio (OR) = 1.56; 95% confidence interval (CI), 1.02 to 2.40) and had a lower overall health status score (p = 0.02). There were no differences in health or functional status at 9 months. A higher proportion of participants consulted the general practitioner (GP) in the 3 months following an X-ray (OR = 2.72; 95% CI, 1.80 to 4.10). There were no differences in use of any other services, medication use or sickness absence at 3 or 9 months. No serious spinal pathology was identified in either group. The commonest X-ray reports were of discovertebral degeneration and normal findings. Many patients did not perceive their information needs were met within the consultation. Satisfaction with care was greater in the group receiving radiography at 9 months. Participants randomised to receive an X-ray were not less worried, or more reassured about serious disease causing their low back pain. Satisfaction was associated with meeting participants' information needs and reduced belief in the necessity for investigations for low back pain, including X-rays and blood tests. In both groups, at 3 and 9 months 80% of participants would choose to have an X-ray if the choice was available. Participants in the patient preference group achieved marginally better outcomes than those randomised to a treatment group, but the clinical significance of these differences is unclear. Lumbar spine radiography was associated with a net economic loss at 3 and 9 months. CONCLUSIONS: Lumbar spine radiography in primary care patients with low back pain of at least 6 weeks duration is not associated with improved functioning, severity of pain or overall health status, and is associated with an increase in GP workload. Participants receiving X-rays are more satisfied with their care, but are not less worried or more reassured about serious disease causing their low back pain. CONCLUSIONS - RECOMMENDATIONS FOR FURTHER RESEARCH: Further work is required to develop and test an educational package that educates patients and GPs about the utility of radiography and provides strategies for identifying and meeting the information needs of patients, and the needs of patients and GPs to be reassured about missing serious disease. Guidelines on the management of low back pain in primary care should be consistent about not recommending lumbar spine radiography in patients with low back pain in the absence of red flags for serious spinal pathology, even if the pain has persisted for at least 6 weeks.

Adult↗
PubMed2001

A metadata framework for interoperating heterogeneous genome data using XML.

The rapid advances in the Human Genome Project and genomic technologies have produced massive amounts of data populated in a large number of network-accessible databases. These technological advances and the associated data can have a great impact on biomedicine and healthcare. To answer many of the biologically or medically important questions, researchers often need to integrate data from a number of independent but related genome databases. One common practice is to download data sets (text files) from various genome Web sites and process them by some local programs. One main problem with this approach is that these programs are written on a case-by-case basis because the data sets involved are heterogeneous in structure. To address this problem, we define metadata that maps these heterogeneously structured files into a common eXtensible Markup Language (XML) structure to facilitate data interoperation. We illustrate this approach by interoperating two sets of essential yeast genes that are stored in two yeast genome databases (MIPS and YPD).

Databases, Genetic↗
PubMed2000

Alendronate for the treatment of osteoporosis in men.

BACKGROUND: Despite its association with disability, death, and increased medical costs, osteoporosis in men has been relatively neglected as a subject of study. There have been no large, controlled trials of treatment in men. METHODS: In a two-year double-blind trial, we studied the effect of 10 mg of alendronate or placebo, given daily, on bone mineral density in 241 men (age, 31 to 87 years; mean, 63) with osteoporosis. Approximately one third had low serum free testosterone concentrations at base line; the rest had normal concentrations. Men with other secondary causes of osteoporosis were excluded. All the men received calcium and vitamin D supplements. The main outcome measures were the percent changes in lumbar-spine, hip, and total-body bone mineral density. RESULTS: The men who received alendronate had a mean (+/-SE) increase in bone mineral density of 7.1+/-0.3 percent at the lumbar spine, 2.5+/-0.4 percent at the femoral neck, and 2.0+/-0.2 percent for the total body (P<0.001 for all comparisons with base line). In contrast, men who received placebo had an increase in lumbar-spine bone mineral density of 1.8+/-0.5 percent (P<0.001 for the comparison with base line) and no significant changes in femoral-neck or total-body bone mineral density. The increase in bone mineral density in the alendronate group was greater than that in the placebo group at all measurement sites (P<0.001). The incidence of vertebral fractures was lower in the alendronate group than in the placebo group (0.8 percent vs. 7.1 percent, P=0.02). Men in the placebo group had a 2.4-mm decrease in height, as compared with a decrease of 0.6 mm in the alendronate group (P=0.02). Alendronate was generally well tolerated. CONCLUSIONS: In men with osteoporosis, alendronate significantly increases spine, hip, and total-body bone mineral density and helps prevent vertebral fractures and decreases in height.

Adult↗
PubMed2000

Yeast homolog of human SAG/ROC2/Rbx2/Hrt2 is essential for cell growth, but not for germination: chip profiling implicates its role in cell cycle regulation.

In an attempt to understand the signaling pathway mediating redox-induced apoptosis, we cloned SAG, an evolutionarily conserved zinc RING finger gene that, when overexpressed, protects cells from apoptosis induced by redox agents. Here we report functional characterization of SAG by the use of yeast genetics approach. Targeted disruption of ySAG, yeast homolog of human SAG, and subsequent tetrad analysis revealed that ySAG is required for yeast viability. Complementation experiment showed that the lethal phenotype induced by the ySAG deletion is fully rescued by wildtype SAG, but not by several hSAG mutants. Complementation experiment has also confirmed that ySAG is essential for normal vegetative growth, rather than being required for sporulation. Furthermore, cell death induced by SAG deletion was accompanied by cell enlargement and abnormal cell cycle profiling with an increased DNA content. Importantly, SAG was found to be the second family member of Rbx (RING box protein) or ROC (Regulator of cullins) or Hrt that is a component of SCF E3 ubiquitin ligase. Indeed, like ROC1/Rbx1/Hrt1, SAG binds to Cul1 and SAG-Cul1 complex has ubiquitin ligase activity to promote poly-ubiquitination of E2/Cdc34. This ligase activity is required for complementation of death phenotype induced by ySAG disruption. Finally, chip profiling of the entire yeast genome revealed induction of several G1/S as well as G2/M checkpoint control genes upon SAG withdrawal. Thus, SAG appears to control cell cycle progression in yeast by promoting ubiquitination and degradation of cell cycle regulatory proteins. Oncogene (2000) 19, 2855 - 2866

Carrier Proteins↗
PubMed2000

Primary care groups. Pie in the sky.

The proposed formula for allocating funds to primary care groups using census data raises concerns about equity. The proposed formula is based on health needs, but these are difficult to define at practice level. Research applying the proposed formula to 199 practices showed it was more suitable for PCGs than individual practices.

Demography↗
PubMed2000

TRIPLES: a database of gene function in Saccharomyces cerevisiae.

Using a novel multipurpose mini-transposon, we have generated a collection of defined mutant alleles for the analysis of disruption phenotypes, protein localization, and gene expression in Saccharomyces cerevisiae. To catalog this unique data set, we have developed TRIPLES, a Web-accessible database of TRansposon-Insertion Phenotypes, Localization and Expression in Saccharomyces. Encompassing over 250 000 data points, TRIPLES provides convenient access to information from nearly 7800 transposon-mutagenized yeast strains; within TRIPLES, complete data reports of each strain may be viewed in table format, or if desired, downloaded as tab-delimited text files. Each report contains external links to corresponding entries within the Saccharomyces Genome Database and International Nucleic Acid Sequence Data Library (GenBank). Unlike other yeast databases, TRIPLES also provides on-line order forms linked to each clone report; users may immediately request any desired strain free-of-charge by submitting a completed form. In addition to presenting a wealth of information for over 2300 open reading frames, TRIPLES constitutes an important medium for the distribution of useful reagents throughout the yeast scientific community. Maintained by the Yale Genome Analysis Center, TRIPLES may be accessed at http://ycmi.med.yale.edu/ygac/triples.htm

DNA Transposable Elements↗
PubMed2000

In situ femoral dual-energy X-ray absorptiometry related to ash weight, bone size and density, and its relationship with mechanical failure loads of the proximal femur.

The objective of this study was to directly compare in situ femoral dual-energy X-ray absorptiometry (DXA) and in vitro chemical analysis (ash weight and calcium) with mechanical failure loads of the proximal femur, and to determine the influence of bone size (volume) and density on mechanical failure and DXA-derived areal bone mineral density (BMD, in g/cm2). We performed femoral DXA in 52 fixed cadavers (age 82.1 +/- 9.7 years; 30 male, 22 female) with intact skin and soft tissues. The femora were then excised, mechanically loaded to failure in a stance phase configuration, their volume measured with a water displacement method (proximal neck to lesser trochanter), and the ash weight and calcium content of this region determined by chemical analysis. The correlation coefficient between the bone mineral content (measured in situ with DXA) and the ash weight was r = 0.87 (standard error of the estimate = 16%), the ash weight allowing for a better prediction of femoral failure loads (r = 0.78; p < 0.01) than DXA (r = 0.67; p < 0.01). The femoral volume (r = 0.61; p < 0.01), but not the volumetric bone density (r = 0.26), was significantly associated with the failure load. The femoral bone volume had a significant impact (r = 0.35; p < 0.01) on the areal BMD (DXA), and only 63% of the variability of bone volume could be predicted (based on the basis of body height, weight and femoral projectional bone area. The results suggest that accuracy errors of femoral DXA limit the prediction of mechanical failure loads, and that the influence of bone size on areal BMD cannot be fully corrected by accounting for body height, weight and projected femoral area.

Absorptiometry, Photon↗
PubMed2000

An integrated web interface for large-scale characterization of sequence data.

Large-scale genome projects require the analysis of large amounts of raw data. This analysis often involves the application of a chain of biology-based programs. Many of these programs are difficult to operate because they are non-integrated, command-line driven, and platform-dependent. The problem is compounded when the number of data files involved is large, making navigation and status-tracking difficult. To demonstrate how this problem can be addressed, we have created a platform-independent Web front end that integrates a set of programs used in a genomic project analyzing gene function by transposon mutagenesis in Saccharomyces cerevisiae. In particular, these programs help define a large number of transposon insertion events within the yeast genome, identifying both the precise site of transposon insertion as well as potential open reading frames disrupted by this insertion event. Our Web interface facilitates this analysis by performing the following tasks. Firstly, it allows each of the analysis programs to be launched against multiple directories of data files. Secondly, it allows the user to view, download, and upload files generated by the programs. Thirdly, it indicates which sets of data directories have been processed by each program. Although designed specifically to aid in this project, our interface exemplifies a general approach by which independent software programs may be integrated into an efficient protocol for large-scale genomic data processing.

Clinical Laboratory Information Systems↗
PubMed2000

A randomized trial of nasal spray salmon calcitonin in postmenopausal women with established osteoporosis: the prevent recurrence of osteoporotic fractures study. PROOF Study Group.

PURPOSE: We conducted a 5-year, double-blind, randomized, placebo-controlled study to determine whether salmon calcitonin nasal spray reduced the risk of new vertebral fractures in postmenopausal women with osteoporosis. SUBJECTS AND METHODS: A total of 1,255 postmenopausal women with established osteoporosis were randomly assigned to receive salmon calcitonin nasal spray (100, 200, or 400 IU) or placebo daily. All participants received elemental calcium (1,000 mg) and vitamin D (400 IU) daily. Vertebral fractures were assessed with lateral radiographs of the spine. The primary efficacy endpoint was the risk of new vertebral fractures in the salmon calcitonin nasal spray 200-IU group compared with the placebo group. RESULTS: During 5 years, 1,108 participants had at least one follow-up radiograph. A total of 783 women completed 3 years of treatment, and 511 completed 5 years. The 200-IU dose of salmon calcitonin nasal spray significantly reduced the risk of new vertebral fractures by 33% compared with placebo [200 IU: 51 of 287, placebo: 70 of 270, relative risk (RR) = 0.67, 95% confidence interval (CI): 0.47- to 0.97, P = 0.03]. In the 817 women with one to five prevalent vertebral fractures at enrollment, the risk was reduced by 36% (RR = 0.64, 95% CI: 0.43- to 0.96, P = 0.03). The reductions in vertebral fractures in the 100-IU (RR = 0.85, 95% CI: 0.60- to 1.21) and the 400-IU (RR = 0.84, 95% CI: 0.59- to 1.18) groups were not significantly different from placebo. Lumbar spine bone mineral density increased significantly from baseline (1% to 1. 5%, P<0.01) in all active treatment groups. Bone turnover was inhibited, as shown by suppression of serum type-I collagen cross-linked telopeptide (C-telopeptide) by 12% in the 200-IU group (P <0.01) and by 14% in the 400-IU group (P<0.01) as compared with placebo. CONCLUSION: Salmon calcitonin nasal spray at a dose of 200 IU daily significantly reduces the risk of new vertebral fractures in postmenopausal women with osteoporosis.

Aged↗
PubMed2000

Cerebral arterial gas embolism by helium: an unusual case successfully treated with hyperbaric oxygen and lidocaine.

A 27-year-old man inhaled helium from an unregulated pressurized cylinder and underwent cerebral arterial gas embolism (CAGE), leaving him blind and with radiologic evidence initially suggesting cortical infarction. There was complete recovery of vision and substantial regression of the radiologic changes after 4 hyperbaric oxygen treatments and a 54-hour lidocaine infusion, which began 6 hours after the accident. This is the second reported case of CAGE occurring by this mechanism and the first case of unequivocal CAGE in which lidocaine has been used as an adjunctive treatment with hyperbaric oxygen.

Adult↗
PubMed2000

Neural and muscular receptors for motilin in the rabbit colon.

Motilin receptors were classically recognized in the gastroduodenal area, where they help to regulate interdigestive motility. More recently, motilin receptors were identified in the colon where their biologic significance remains unclear. We aimed here to characterize the motilin receptors of the rabbit colon. Distal colon and duodenum were obtained from sacrificed rabbits. Tissues homogenized by Polytron were submitted to differential centrifugation to obtain neural synaptosomes or smooth muscle plasma membranes enriched solutions. Motilin binding to these membranes was determined by the displacement of (125)I MOT by the native peptide MOT 1-22, or by peptide analogues MOT 1-12 [CH(2)NH](10-11) or GM-109 and by erythromycin derivative GM-611. Motilin binding capacity was maximum in colon nerves (49.5 +/- 6.5 fmol/mg protein vs. 19.9 +/- 2.5 in colon muscles or 9.4 +/- 2.8 and 6.6 +/- 1.2 in duodenal muscles and antral nerves respectively); all tissues expressed similar affinity for MOT 1-22, and the motilin agonist GM-611 bound equally to neural or muscle tissues from the rabbit colon; the synthetic antagonist MOT 1-12 [CH(2)NH](10-11) showed greater affinity for colon nerves than for colon muscles (plC50: 7.23 +/- 0.07 vs. 6.75 +/- 0.03). Similar results were obtained with the peptide antagonist GM-109; receptor affinity toward MOT 1-12 [CH(2)NH(10-11)] was always five times superior in neural tissues, whether they came from the colon or the antrum, than in muscle tissues, whether they were obtained from colon or from duodenum. Motilin receptors are found in very high concentration in nerves and in muscles from rabbit colon; specific motilin receptor subtypes are identified in nerves (N) and muscles (M) of the rabbit colon; N and M receptor subtypes seem independent of the organ location.

Animals↗
PubMed2000

Neuropsychological change in young people at high risk for schizophrenia: results from the first two neuropsychological assessments of the Edinburgh High Risk Study.

BACKGROUND: Studies of groups of individuals who have a genetically high risk of developing schizophrenia, have found neuropsychological impairments that highlight likely trait markers of the schizophrenic genotype. This paper describes the change in neuropsychological function and associations with psychiatric state of high risk participants during the first two assessments of the Edinburgh High Risk Study. METHODS: Seventy-eight high risk participants and 22 normal controls, age and sex matched completed two neuropsychological assessments 18 months to 2 years apart. The areas of function assessed include intellectual function, executive function, learning and memory, and verbal ability and language. RESULTS: The high risk participants performed significantly worse on particular tests of verbal memory and executive function over the two assessments than matched controls. Those high risk participants who experienced psychotic symptoms were found to exhibit a decline in IQ and perform worse on tests of verbal memory and executive function than those without symptoms. An increase in psychotic symptoms between the two assessments in the high risk group was found to be associated with an apparent decline in IQ and memory. CONCLUSIONS: The results suggest that the development of psychotic symptoms is preceded by a decline in IQ and memory. This may reflect a general and a more specific disease process respectively.

Adolescent↗