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D Parry

Publications and source records attributed to D Parry.

At least 19 recordsLinked to original sources
PubMed2001

Binding and recognition of GATATC target sequences by the EcoRV restriction endonuclease: a study using fluorescent oligonucleotides and fluorescence polarization.

Oligonucleotides labeled with hexachlorofluorescein (hex) have enabled the interaction of the restriction endonuclease EcoRV with DNA to be evaluated using fluorescence anisotropy. The sensitivity of hex allowed measurements at oligonucleotide concentrations as low as 1 nM, enabling K(D) values in the low nanomolar range to be measured. Both direct titration, i.e., addition of increasing amounts of the endonuclease to hex-labeled oligonucleotides, and displacement titration, i.e., addition of unlabeled oligonucleotide to preformed hex-oligonucleotide/EcoRV endonuclease complexes, have been used for K(D) determination. Displacement titration is the method of choice; artifacts due to any direct interaction of the enzyme with the dye are eliminated, and higher fluorescent-labeled oligonucleotide concentrations may be used, improving signal-to-noise ratio. Using this approach (with three different oligonucleotides) we found that the EcoRV restriction endonuclease showed a preference of between 1.5 and 6.5 for its GATATC target sequence at pH 7.5 and 100 mM NaCl, when the divalent cation Ca2+ is absent. As expected, both the presence of Ca2+ and a decrease in pH value stimulated the binding of specific sequences but had much less effect on nonspecific ones.

Binding, Competitive↗
PubMed2001

The Patient Care Notebook: quality improvement on a rehabilitation unit.

BACKGROUND: Shortened lengths of stay in acute and rehabilitation hospitals, continuing financial pressures on all postacute care services, and increasing out-of-pocket health care costs for patients and families challenge rehabilitation hospitals' patient education and discharge planning processes. Spaulding Rehabilitation Hospital (Boston) introduced a patient care notebook in a 15-bed satellite unit and pilot tested its contribution to the patient education and discharge planning process. DEVELOPING THE NOTEBOOK: The three-ring binder notebook included sections on medical appointments and phone numbers, understanding illness and medical care, coping with illness, physical activities, recommendations for the home, and community resources, with both standard and patient-specific information. RESULTS: Most of the patients and caregivers who received the notebooks found them to be helpful, and most staff indicated that the notebook improved the teaching process. Telephone calls to the unit after home discharges decreased form 28 calls for 11 discharges to 6 calls for 21 discharges after the notebook began to be used regularly. DISCUSSION: Staff felt that the process of using the notebook helped focus attention on teaching during the entire course of a patient's hospitalization rather than just a day or two before discharge. The patient care notebook process is being introduced to the entire hospital and to all patients, regardless of discharge location and the patient's literacy or proficiency with English. CONCLUSION: In using the notebook, the QI team, and the entire unit staff, learned about the complexities of QI, patient education, and discharge planning. The notebook process was implemented throughout the hospital a little more than a year after the completion of the pilot project.

Aged↗
PubMed2001

The use of a moulded metacarpal brace versus neighbour strapping for fractures of the little finger metacarpal neck.

Seventy-three patients with fractures of the neck of the little finger metacarpal were randomized to treatment with a moulded metacarpal brace or neighbour strapping. Sixty-five of these attended for follow-up at 3 weeks. Both treatment modalities permitted a functional range of movement, but patients treated with the metacarpal brace had significantly less pain than those treated with neighbour strapping, and this facilitated an early return to work.

Adolescent↗
PubMed2001

Bifrontal decompressive craniectomy in the management of posttraumatic intracranial hypertension.

Bifrontal decompressive craniectomy has been used on an ad hoc basis for the treatment of post-traumatic intracranial hypertension for more than thirty years. In this observational study we report the clinical outcome and physiological effects of the procedure in a series of 26 patients with refractory intracranial hypertension treated on a protocol driven basis. Bifrontal decompressive craniectomy was associated with significant reductions in mean ICP from 37.5 to 18.1 mmHg (p = 0.003). In addition, craniectomy reduced the amplitude of ICP waves (p < 0.02) and increased compensatory reserve (p < 0.05). A favourable outcome was achieved in 69% of patients; 8% were severely disabled and 23% died. We conclude that this study provides pathophysiological evidence that bifrontal decompressive craniectomy significantly reduces posttraumatic intracranial hypertension and improves pressure dynamics. Our results support the continued use of bifrontal decompressive craniectomy in selected patients after head injury.

Adolescent↗
PubMed2001

The cost-effectiveness of magnetic resonance imaging for investigation of the knee joint.

OBJECTIVES: This study considered the role of magnetic resonance imaging (MRI) in the diagnosis of knee injuries in a district general hospital (DGH) setting. The principal objective was to identify whether the use of MRI had a major impact on the clinical management of patients presenting with chronic knee problems, in whom surgery was being considered, whether it reduced overall costs and whether it improved patient outcome. In addition, the research: (1) explored the 'diagnostic accuracy' of initial clinical investigation of the knee by an orthopaedic trainee, consultant knee specialist and consultant radiologist; (2) considered the variability and diagnostic accuracy of interpretations of knee MRI investigations between radiologists; (3) measured the strength of preference for the potential diagnostic/therapeutic impact of knee MRI (i.e. the avoidance of surgery). METHODS - RANDOMISED CONTROLLED TRIAL: The research was based on a single-centre randomised controlled trial conducted at Kent and Canterbury Hospital. Patients attending with knee problems in whom surgery was being considered were recruited from routine orthopaedic clinics. Most patients had been referred by their general practitioner. Patients were randomised to either investigation using an MRI scan (MRI trial arm) or investigation using arthroscopy (no-MRI trial arm). The study investigated the benefits of knee MRI at two levels: diagnostic/therapeutic impact (i.e. avoidance of surgery) and patient outcome (using the Short Form with 36 items and EQ-5D quality-of-life measurement instruments). Quality of life was assessed at baseline and at 6 and 12 months. Costs were assessed from the perspectives of the NHS and patients. All analyses were by intention to treat. METHODS - SUBSTUDIES (INVESTIGATION OF DIAGNOSTIC ACCURACY): For the investigation of diagnostic accuracy of initial clinical investigation, the sample comprised 114 patients recruited in a separate study conducted at St Thomas' Hospital. The sample was drawn from patients presenting at the Accident and Emergency Department with an acute knee injury. All study patients received an MRI scan, but initial diagnosis was made without access to the scan or the radiologist's report. After 12 months, all clinical notes and MRI scans of study patients were reviewed and a final 'reference standard' diagnosis for each patient was reached. Comparison was made between the diagnosis recorded by each clinician (i.e. orthopaedic trainee, knee specialist and consultant radiologist) and the reference diagnosis. METHODS - SUBSTUDIES (INVESTIGATION OF THE GENERALISABILITY OF RESULTS): For this substudy, the MRI images from 80 patients (recruited at St Thomas' Hospital) were interpreted independently by seven consultant radiologists at DGHs and the St Thomas' Hospital MRI radiologist. For each area of the knee, the level of agreement (measured using weighted kappa) between the responses of the eight radiologists and the reference standard diagnosis was assessed. METHODS - SUBSTUDIES (INVESTIGATION OF PREFERENCES): The investigation of potential patient preferences for the diagnostic/therapeutic impact of MRI was explored using a discrete choice conjoint measurement research design. Choices involved selecting between two alternative scenarios described using four attributes, and data were collected from 585 undergraduate sports science students and analysed using a random-effects probit model. RESULTS - RANDOMISED CONTROLLED TRIAL: The trial recruited 118 patients (59 randomly allocated to each arm). The two groups were similar in important respects at baseline. The central finding was of no statistically significant differences between groups in all measures of health outcome, although a trend in favour of the no-MRI group was observed. However, the use of MRI was found to be associated with a positive diagnostic/therapeutic impact: a significantly smaller proportion of patients in the MRI group underwent surgery (MRI = 0.41, no-MRI = 0.71; p = 0.001). There was a similar mean overall NHS cost for both groups. RESULTS - SUBSTUDIES (INVESTIGATION OF DIAGNOSTIC ACCURACY): The exploration of diagnostic accuracy found that, when compared to orthopaedic trainees (44% correct diagnoses) or to radiologists reporting an MRI scan (68% correct diagnoses), the accuracy rate was higher for knee specialists (72% correct diagnoses). RESULTS - SUBSTUDIES (INVESTIGATION OF THE GENERALISABILITY OF RESULTS): This generalisability study indicated that, in general terms, radiologists in DGHs provide accurate interpretations of knee MRI images that are similar to a radiologist at a specialist centre. The one area of the knee for which this did not hold was the lateral collateral ligament. RESULTS - SUBSTUDIES (INVESTIGATION OF PREFERENCES): The central finding for this substudy was that, on average and within the range specified, choices in this group of potential patients were not significantly influenced by variation in the chance of avoiding surgery. CONCLUSIONS - IMPLICATIONS FOR HEALTHCARE: The evidence presented in this report supports the conclusions that the use of MRI in patients presenting at DGHs with chronic knee problems in whom arthroscopy was being considered did not increase NHS costs overall, was not associated with significantly worse outcomes and avoided surgery in a significant proportion of patients. CONCLUSIONS - RECOMMENDATIONS FOR FURTHER RESEARCH (IN PRIORITY ORDER): (1) The trial data demonstrated that the use of MRI in patients with chronic knee problems reduced the need for surgery. However, the link between diagnostic processes and changes in health outcome is indirect and the finding of no-MRI-related effect on health outcome may, therefore, be a consequence of the limited power of the trial. Further research to confirm (or contradict) these findings would be valuable. (2) The investigation of diagnostic accuracy involved comparison with a reference diagnosis established by a panel of two clinical members of the research team. It would be interesting to explore the extent to which the results would differ using an external panel. (3) The result from the preference study, indicating that the potential diagnostic/therapeutic impact of knee MRI was not highly valued, is a surprising finding that would be important to explore in general public or patient populations. (4) The focus for the trial-based aspects of this research was the DGH and patients presenting with chronic knee problems who were being considered for surgery. Care should be taken in generalising from these results to other patient groups (e.g. acute knee injuries) or to other settings (e.g. specialist centres). Further clinical trials would be required in order to answer such questions.

Adolescent↗
PubMed2001

Patient costs in anticoagulation management: a comparison of primary and secondary care.

BACKGROUND: The demand for anticoagulation management is increasing. This has led to care being provided in non-hospital settings. While clinical studies have similarly demonstrated good clinical care in these settings, it is still unclear as to which alternative is the most efficient. AIM: To determine the costs borne by patients when attending an anticoagulation management clinic in either primary or secondary care and to use this information to consider the cost-effectiveness of anticoagulation management in primary and secondary care, both from the National Health Service and patient perspectives. DESIGN OF STUDY: Observational study comparing two cohorts of patients currently attending anticoagulation management clinics. SETTING: Four primary care clinics in Birmingham and one in Warwickshire, and the haematology clinics at the University of Birmingham Hospitals Trust and the City Hospital NHS Trust. METHOD: The survey of patients attending the clinics was used to ascertain patient costs. This information was then used in conjunction with the findings of a recent randomised controlled trial to establish cost-effectiveness. RESULTS: Patient costs were lower in primary care than in secondary care settings; the mean (standard deviation) costs per visit were Pound Sterling6.78 (Pound Sterling5.04) versus Pound Sterling14.58 (Pound Sterling9.08). While a previous cost-effectiveness analysis from a health sector perspective alone found a higher cost for primary care, the adoption of the societal perspective lead to a marked change in the result: a similar total cost per patient in both sectors. CONCLUSION: There are significantly higher costs borne by patients attending secondary care anticoagulation management clinics than similar patients attending primary care clinics. This study also demonstrates that the perspective adopted in an economic evaluation can influence the final result.

Aged↗
PubMed2000

Anticoagulation management in primary care: a trial-based economic evaluation.

The demand for anticoagulation management is increasing because of a widening of the indications of treatment. A primary care clinic using near-patient testing and computer decision support software is one model of care to meet this increased demand. The study aimed to determine the cost and cost-effectiveness of primary care-based anticoagulation management in comparison with 'traditional' hospital care-based provision by means of a cost-effectiveness analysis using data from a Birmingham-based multicentre randomized controlled trial. The costs per patient per year in primary care were pound170 [95% confidence interval (CI) pound149-190] vs. pound69 (95% CI pound57-81). Sensitivity analysis demonstrated that the cost in primary care could be reduced to under pound100 per patient per year under plausible changes in the variables. Primary care provides similar levels of control to secondary care for patients on anticoagulation therapy. There is an increased cost of managing patients in primary care and at no point did primary care become a lower cost option than secondary care. Local decision-makers need to assess the increased cost of primary care anticoagulation management in terms of the potential reductions in high-cost serious adverse events.

Aged↗
PubMed2000

Cyclin D2 is essential for BCR-mediated proliferation and CD5 B cell development.

Progression into G(1) in B lymphocytes is regulated by cyclins D2 and D3, components of the cell cycle machinery currently believed to have overlapping and potentially redundant roles in cell cycle control. To study the specific role of cyclin D2 in B lymphocyte proliferation, we examined B cells from cyclin D2(-/-) mice and demonstrate a specific requirement for cyclin D2 in BCR- but not CD40- or lipopolysaccharide-induced proliferation. Furthermore, conventional B cell development proceeds normally in the mutant mice; however, the CD5 B cell compartment is dramatically reduced, suggesting that cyclin D2 is important in CD5 B cell development as well as antigen-dependent B cell clonal expansion.

Animals↗
PubMed1999

Reverse genetic analysis of Caenorhabditis elegans presenilins reveals redundant but unequal roles for sel-12 and hop-1 in Notch-pathway signaling.

Mutations in the human presenilin genes PS1 and PS2 cause early-onset Alzheimer's disease. Studies in Caenorhabditis elegans and in mice indicate that one function of presenilin genes is to facilitate Notch-pathway signaling. Notably, mutations in the C. elegans presenilin gene sel-12 reduce signaling through an activated version of the Notch receptor LIN-12. To investigate the function of a second C. elegans presenilin gene hop-1 and to examine possible genetic interactions between hop-1 and sel-12, we used a reverse genetic strategy to isolate deletion alleles of both loci. Animals bearing both hop-1 and sel-12 deletions displayed new phenotypes not observed in animals bearing either single deletion. These new phenotypes-germ-line proliferation defects, maternal-effect embryonic lethality, and somatic gonad defects-resemble those resulting from a reduction in signaling through the C. elegans Notch receptors GLP-1 and LIN-12. Thus SEL-12 and HOP-1 appear to function redundantly in promoting Notch-pathway signaling. Phenotypic analyses of hop-1 and sel-12 single and double mutant animals suggest that sel-12 provides more presenilin function than does hop-1.

Animals↗
PubMed1999

Cyclin E associates with BAF155 and BRG1, components of the mammalian SWI-SNF complex, and alters the ability of BRG1 to induce growth arrest.

SWI-SNF complexes have been implicated in transcriptional regulation by chromatin remodeling. We have identified an interaction between two components of the mammalian SWI-SNF complex and cyclin E, an essential cell cycle regulatory protein required for G1/S transition. BRG1 and BAF155, mammalian homologs of yeast SWI2 and SWI3, respectively, are found in cyclin E complexes and are phosphorylated by cyclin E-associated kinase activity. In this report, we show that overexpression of BRG1 causes growth arrest and induction of senescence-associated beta-galactosidase activity, which can be overcome by cyclin E. Our results suggest that cyclin E may modulate the activity of the SWI-SNF apparatus to maintain the chromatin in a transcriptionally permissive state.

Amino Acid Sequence↗
PubMed1999

Cyclin D-CDK subunit arrangement is dependent on the availability of competing INK4 and p21 class inhibitors.

The D-type cyclins and their major kinase partners CDK4 and CDK6 regulate G0-G1-S progression by contributing to the phosphorylation and inactivation of the retinoblastoma gene product, pRB. Assembly of active cyclin D-CDK complexes in response to mitogenic signals is negatively regulated by INK4 family members. Here we show that although all four INK4 proteins associate with CDK4 and CDK6 in vitro, only p16(INK4a) can form stable, binary complexes with both CDK4 and CDK6 in proliferating cells. The other INK4 family members form stable complexes with CDK6 but associate only transiently with CDK4. Conversely, CDK4 stably associates with both p21(CIP1) and p27(KIP1) in cyclin-containing complexes, suggesting that CDK4 is in equilibrium between INK4 and p21(CIP1)- or p27(KIP1)-bound states. In agreement with this hypothesis, overexpression of p21(CIP1) in 293 cells, where CDK4 is bound to p16(INK4a), stimulates the formation of ternary cyclin D-CDK4-p21(CIP1) complexes. These data suggest that members of the p21 family of proteins promote the association of D-type cyclins with CDKs by counteracting the effects of INK4 molecules.

Amino Acid Sequence↗