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Biomedical subjects

G Pearson

Publications and source records attributed to G Pearson.

At least 37 records · Page 2Linked to original sources

Ibuprofen versus other non-steroidal anti-inflammatory drugs: use in general practice and patient perception.

OBJECTIVE: To investigate whether ibuprofen was as well-regarded by patients as other non-steroidal anti-inflammatory drugs (NSAIDs). DESIGN: Questionnaire sent to 1137 consecutive recipients of an NSAID prescription from 21 doctors in six general practices with computerized records. Patient responses were subsequently linked to data held on the practice records. SETTING: General practices in and around Nottingham, selected to reflect local variations in number of partners, list size, geographical location, deprivation, prescribing burden and prescribing rate. SUBJECTS: Unselected patients receiving NSAIDs prescribed for all indications for use. MAIN OUTCOME MEASURES: Effectiveness of ibuprofen and other NSAIDs, possible drug related adverse events, patients' overall satisfaction with ibuprofen and other NSAIDs, factors associated with choice of ibuprofen, drug costs of ibuprofen and other NSAIDs. RESULTS: The main NSAIDs used were ibuprofen, diclofenac and naproxen. Ibuprofen use ranged from 1.0% of prescriptions in one practice to 69.1% in another. Although ibuprofen was generally prescribed in low doses, it was perceived by patients as being as effective as the other NSAIDs used, even after allowing for severity of the pre-treatment condition. Overall, 50.5% of patients rated their NSAID the best treatment they had received for their condition with no differences between individual drugs. CONCLUSIONS: Ibuprofen is as highly regarded as other NSAIDs when used in similar circumstances. Switching patients to ibuprofen may be a realistic way of reducing financial and medical costs associated with NSAIDs.

Adolescent↗

Structured interview and uniform assessment improves diagnostic reliability.

OBJECTIVE: To compare a Childhood Uniform Assessment Package (CUAP), including a computerized structured diagnosis, with routine assessment and treatment in public mental health settings. DATA SOURCES/STUDY SETTINGS: Data was collected prospectively on 250 children and adolescents in both public mental health inpatient and outpatient settings in a large metropolitan area and a rural area. STUDY DESIGN: Subjects were randomized to either routine assessment and treatment as usual (ATU) or ATU plus an additional "gold standard" assessment battery Childhood Uniform Assessment Package (CUAP). Outcome measures were taken at admission (baseline), discharge, and again 6 months later. METHODS: The study was conducted at a State Hospital (CUAP, n = 75; ATU, n = 75) and a Community Mental Health center (CUAP, n = 50; ATU, n = 50). The "gold standard" diagnostic process was established at the Children's Medical Center-Dallas. Research focused on a comparison of the CUAP diagnostic process to the existing diagnostic process (ATU) and the service delivery system of an inpatient and outpatient public sector clinical treatment setting. PRINCIPAL FINDINGS: A bachelor's level individual can be trained to administer a highly reliable diagnostic battery to meet a "gold standard," suggesting a possible cost-effective way to assist in diagnostic evaluations. Higher reliability was found between this standardized assessment package (CUAP) and inpatient physicians than for outpatient physicians. The highest interrater reliabilities were found for attention deficit and substance abuse disorders, less so for the other behavior disorders. The use of CUAP results in more reliable diagnoses in public settings than those provided by typical clinical staff by identifying mood and anxiety disorders (disorders with the lowest reliability) with better reliability. The addition of "gold standard" diagnostic assessments (CUAP) did not appear to affect length of stay, number of medication changes, use of seclusion or restraints, and other behavioral interventions in the inpatient setting. Outpatient follow-up services did not differ for CUAP versus ATU either. CONCLUSIONS: A standard uniform assessment package that includes a structured diagnostic instrument can improve overall diagnostic reliability but may not have a significant overall impact in clinical treatment strategies or outcomes without additional intervention to assure proper use of the information. A well-trained bachelor's level assistant can administer such a battery.

Adolescent↗

Implementing and maintaining school-based mental health services in a large, urban school district.

The Dallas (Texas) Public Schools established the first school-based health center in the United States in 1969. In 1993 a partnership between two school principals, a school mental health professional, and the medical director of the county mental health center was the impetus for the first comprehensive school-based mental health center in Texas. In 1995 the programs joined together as Youth and Family Centers (YFCs) to provide physical health, mental health, and other support services to students and their families. The 10 strategically located school-based centers are directed by licensed mental health professionals employed by the district who lead a multidisciplinary team of physical health and mental health providers. Students served by the YFCs have fewer discipline problems, course failures, and school absences.

Adolescent↗

Deep venous thrombosis: detection by using indirect CT venography. The Pulmonary Angiography-Indirect CT Venography Cooperative Group.

PURPOSE: To assess the clinical benefits of performing indirect computed tomographic (CT) venography after pulmonary CT angiography to detect deep venous thrombosis (DVT) in patients suspected of having a pulmonary embolism. MATERIALS AND METHODS: The authors prospectively enrolled 541 consecutive patients who underwent pulmonary CT angiography for suspected pulmonary embolism at seven institutions. Using a protocol that optimizes venous enhancement without additional contrast material injection, the authors obtained contiguous images from the pelvis to the popliteal fossa. Ultrasonography (US) also was performed in 116 patients. RESULTS: DVT was found at indirect CT venography in 45 (8%), and pulmonary embolism was found at pulmonary CT angiography in 91 (17%) of 541 patients. Among the 45 patients with DVT, DVT occurred in 16 patients who had no pulmonary embolism at pulmonary CT angiography, which increased the diagnosis of thromboembolic disease by 18%. Among 116 patients who underwent US and indirect CT venography, 15 had DVT at US, and in all 15, DVT also was seen at indirect CT venography. In four additional cases, DVT was seen at only indirect CT venography. CONCLUSION: Among patients suspected to have pulmonary embolism, a substantial number had DVT in the absence of pulmonary embolism. Combined pulmonary CT angiography-indirect CT venography can depict these cases with accuracy comparable to that of US and thus could have a significant effect on patient care.

Adolescent↗

Contribution of the ERK5/MEK5 pathway to Ras/Raf signaling and growth control.

The activity of the catalytic domain of the orphan MAP kinase ERK5 is increased by Ras but not Raf-1 in cells, which suggests that ERK5 might mediate Raf-independent signaling by Ras. We found that Raf-1 does contribute to Ras activation of ERK5 but in a manner that does not correlate with Raf-1 catalytic activity. A clue to the mechanism of action of Raf-1 on ERK5 comes from the observation that endogenous Raf-1 binds to endogenous ERK5, suggesting the involvement of regulatory protein-protein interactions. This interaction is specific because Raf-1 binds only to ERK5 and not ERK2 or SAPK. Finally, we demonstrate the ERK5/MEK5 pathway is required for Raf-dependent cellular transformation and that a constitutively active form of MEK5, MEK5DD, synergizes with Raf to transform NIH 3T3 cells. These observations suggest that ERK5 plays a large role in Raf-1-mediated signal transduction.

Animals↗

Basal cell carcinoma of the lower extremities.

BACKGROUND: The most common malignancy in the USA is basal cell carcinoma. It is most prevalent on the head and neck, but can occur elsewhere. We sought to determine the frequency of basal cell carcinomas arising on the lower extremities, as well as the gender of affected patients, the histologic subtype, and the specific sites of involvement. METHODS: We reviewed cases submitted to the Vanderbilt Dermatopathology Service between 1994 and 1997 which were diagnosed as basal cell carcinoma. A subset of 150 cases which arose on the lower extremities and a control group of 150 cases which arose at other anatomic sites were studied further. RESULTS: A significantly greater number of basal cell carcinomas of the lower extremities arose in women, were of the superficial subtype, and were found below the knee; 59% of basal cell carcinomas in both sexes arose on the right limb. CONCLUSION: Basal cell carcinomas of the lower extremities occur more often in women in the USA and are of the superficial subtype. This may be due to differing patterns of dress and exposure to the sun.

Adult↗

Identification of substrates and regulators of the mitogen-activated protein kinase ERK5 using chimeric protein kinases.

Extracellular signal-regulated protein kinase 5 (ERK5) is a recently discovered orphan mitogen-activated protein kinase for which no substrates or strong activators have been described. Two ERK5 chimeras were created as a novel approach to discover its substrates and upstream regulators. One chimeric protein contained the N-terminal domain of the ERK5 catalytic core (subdomains I-IV) and the C-terminal domain of the ERK2 catalytic core (subdomains V-XI). This chimera was highly responsive to stimuli that regulate ERK2 in vitro and in cells. A second chimeric protein consisted of the N-terminal domain of ERK2 (subdomains I-IV) and the C-terminal domain of the ERK5 catalytic core (subdomains V-XI). This chimera was activated in bacteria by coexpression with a constitutively active mutant of MEK1. Using the activated chimera, we identified three in vitro substrates of ERK5. Assaying ERK5 activity in immune complexes with one of these substrates, c-Myc, we determined that the ERK5 catalytic domain is activated by V12 H-Ras and to a lesser extent by phorbol ester but not by constitutively active mutants of Raf-1. Thus, ERK5 is a target of a novel Ras effector pathway that may communicate with c-Myc.

Calcium-Calmodulin-Dependent Protein Kinases↗

Epidemiological study of latent and recent infection by Toxoplasma gondii in pregnant women from a regional population in the U.K.

AIMS: To determine the prevalence of IgG and IgM to Toxoplasma gondii (TG) and predict the incidence of infection during pregnancy and in foetuses. METHODS: Thirteen thousand pregnant women from eastern England were tested at the time of booking for antenatal screening. Screening was carried out for the presence of IgG and IgM anti-TG, followed by confirmation with commercially available assays. RESULTS: Latent infection to TG was found in 7.7% of women and increased with age from 6.8 to 17.8%. Recent infection accounted for an additional 0.4% equally distributed across age groups. No difference was found between urban and rural place of residence. A 1-2% incidence of TG infection every 5 years of age was found. IgM-only cases were mostly false positives and were unsuitable for statistical analysis. On the basis of both IgM and IgG imputed data, TG infection was found significantly higher during the first trimester of pregnancy. Three to sixteen TG-infected foetuses per 10000 pregnancies were predicted. CONCLUSIONS: The east of England has a low prevalence of TG infection and therefore a high, at-risk population of pregnant women. Repeated screening during pregnancy would be expensive, but would detect and possibly prevent infection in approximately 10 neonates per 10000 women.

Adult↗

Secondary dimerization between members of the epidermal growth factor receptor family.

Growth factor receptors of the epidermal growth factor (EGF) receptor family play pivotal roles in the regulation of cell proliferation and differentiation and are involved in the development of human cancers. It has been well documented that these receptors undergo growth factor-stimulated homo- and heterodimerization as a first step in the initiation of signaling cascades. Here we provide evidence for a new mechanism for growth factor-stimulated receptor dimer formation, designated secondary dimerization. The growth factor-induced dimerization and ensuing receptor trans-autophosphorylation results in the dissociation of the original (primary) receptor dimer. Each phosphorylated receptor monomer then interacts with a new (nonphosphorylated) receptor to form a secondary dimer. Treatment of cells with EGF yields Neu-ErbB3 secondary dimers, and heregulin treatment induces the formation of Neu-EGF receptor (secondary) dimers. The ability of EGF and heregulin to stimulate a cascade of dimerization events points to a novel mechanism by which multiple signaling activities and diverse biological responses are initiated by members of the EGF receptor family.

Animals↗

Should paediatric intensive care be centralised? Trent versus Victoria.

BACKGROUND: The mortality rate is lower among children admitted to specialist paediatric intensive care units (ICUs) than among those admitted to mixed adult and paediatric units in non-tertiary hospitals. In the UK, however, few children receive intensive care in specialist paediatric units. We compared the ICU mortality rate in children from the area the Trent Health Authority, UK, with the rate in children from Victoria, Australia, where paediatric intensive care is highly centralised. METHODS: We studied all children under 16 years of age from Trent and Victoria who received intensive care between April 1, 1994, and March 31, 1995. Children younger than 1 month were excluded unless they had cardiac disorders. We developed a logistic regression model that used information gathered at the time of admission to ICU to adjust for risk of mortality. FINDINGS: The rates of admission of children to intensive care were similar for Trent and Victoria (1.22 and 1.18 per 1000 children per year), but the mean duration of an ICU stay was 3.93 days for Trent children compared with 2.14 days for children from Victoria. 74 (7.3%) of the 1014 children from Trent died, compared with 60 (5.0%) of the 1194 children from Victoria. With adjustment for severity of illness at the time of admission to ICU, the odds ratio for the risk of death for Trent versus Victoria was 2.09 (95% CI 1.37-3.19, p < 0.0005). There were 31.7 (14.0-50.4) excess deaths in Trent children, which is equivalent to 42.8% of the deaths in ICU, and 11.1% of all deaths in children between the ages of 1 month and 16 years in Trent. INTERPRETATION: If Trent is representative of the whole country, there are 453 (200-720) excess deaths a year in the UK that are probably due to suboptimal results from paediatric intensive care. If the ratio of paediatric ICUs to children were the same in the UK as in Victoria, there would be only 12 paediatric ICUs in the country. Our findings suggest that substantial reductions in mortality could be achieved if every UK child who needed endotracheal intubation for more than 12-24 h were admitted to one of 12 large specialist paediatric ICUs.

Adolescent↗

Reactivity of synthetic peptides representing selected sections of hepatitis C virus core and envelope proteins with a panel of hepatitis C virus-seropositive human plasma.

A series of 54 synthetic peptides, 15-20 residues long, that represented selected parts of the structural proteins of hepatitis C virus (HCV) were tested for immunoreactivity with a panel of 45 plasma samples from potential blood donors who were known to be seropositive for anti-HCV. Most of the ten peptides that represented the core protein showed reactivity with most of the panel samples. All except one of the 20 peptides that represented non-hypervariable regions of envelope proteins E1 and E2 showed little or no reactivity. In contrast, 18 of the the 24 peptides that represented variants of the hypervariable region 1 of the E2 protein reacted with at least one panel sample. Notably, 40% of the panel samples cross-reacted with two or more different peptides sequences some of which differed by more than 50%. Two panel samples each cross-reacted with seven different peptide sequences. The results suggest a broad anti-hypervariable region antibody specificity in many anti-HCV-seropositive samples and possible limits on the mutability of hypervariable region sequences. The work contributes to understanding the immunogenicity and persistence of HCV.

Amino Acid Sequence↗

Paediatric index of mortality (PIM): a mortality prediction model for children in intensive care.

OBJECTIVE: To develop a logistic regression model that predicts the risk of death for children less than 16 years of age in intensive care, using information collected at the time of admission to the unit. DESIGN: Three prospective cohort studies, from 1988 to 1995, were used to determine the variables for the final model. A fourth cohort study, from 1994 to 1996, collected information from consecutive admissions to all seven dedicated paediatric intensive care units in Australia and one in Britain. RESULTS: 2904 patients were included in the first three parts of the study, which identified ten variables for further evaluation. 5695 children were in the fourth part of the study (including 1412 from the third part); a model that used eight variables was developed on data from four of the units and tested on data from the other four units. The model fitted the test data well (deciles of risk goodness-of-fit test p = 0.40) and discriminated well between death and survival (area under the receiver operating characteristic plot 0.90). The final PIM model used the data from all 5695 children and also fitted well (p = 0.37) and discriminated well (area 0.90). CONCLUSIONS: Scores that use the worst value of their predictor variables in the first 12-24 h should not be used to compare different units: patients mismanaged in a bad unit will have higher scores than similar patients managed in a good unit, and the bad unit's high mortality rate will be incorrectly attributed to its having sicker patients. PIM is a simple model that is based on only eight explanatory variables collected at the time of admission to intensive care. It is accurate enough to be used to describe the risk of mortality in groups of children.

Adolescent↗

Effect of paroxetine and nefazodone on 5-HT1A receptor sensitivity.

Animal experimental studies suggest that the therapeutic effect of selective serotonin re-uptake inhibitors (SSRIs) may involve neuroadaptive changes in pre- and post-synaptic serotonin1A (5-HT1A) receptors. We used the endocrine and hypothermic responses to the 5-HT1A receptor agonist, gepirone (20 mg orally), to assess 5-HT1A receptor sensitivity in 37 healthy male volunteers who were studied before and following random double-blind, allocation to treatment with paroxetine, nefazodone or placebo for 17 days. Following antidepressant drug treatment, hypothermic responses to gepirone were markedly decreased by paroxetine but only slightly diminished by nefazodone. Paroxetine also lowered the growth hormone and cortisol responses to gepirone. There was no change in either hypothermic or endocrine response following placebo treatment. Our results suggest that paroxetine treatment produces a striking attenuation of measures of both pre- and post-synaptic 5-HT1A receptor function. Nefazodone appears to decrease the sensitivity of 5-HT1A autoreceptors to some extent and this effect may contribute to its antidepressant activity.

Adult↗

Silver and fluoride ion release from metal-reinforced glass-ionomer filling materials.

This study was undertaken to examine whether a relationship exists between the composition of metal-containing glass-ionomer cements and ion release from these materials. Conflicting data on silver release from this type of material has been reported and it was felt that further investigation was desirable in view of the increasing use of these materials. In this study, the release of ions, particularly of silver and fluoride, into deionized water and artificial saliva was measured for up to one year. Low levels of silver and copper ions were found in both media. The amounts released from alloy-containing materials were dependent on the amount of alloy present; lesser amounts were leached from cermets. Fluoride ion release was less material-dependent but still lowest for cermets. The use of artificial saliva reduced ion release as did increasing the maturation time prior to immersion in either liquid.

Aluminum↗