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Biomedical subjects

J Wilson

Publications and source records attributed to J Wilson.

At least 271 records · Page 15Linked to original sources

The Spanish Instrument Protocol: design and implementation of a study to evaluate treatment efficacy Instruments for Spanish-speaking patients with Alzheimer's disease. The Alzheimer's Disease Cooperative Study.

Development of improved outcome measures for Alzheimer's disease (AD) clinical trials is a major objective of the Alzheimer's Disease Cooperative Study (ADCS), an NIA-sponsored, multisite clinical trials consortium. The ADCS is committed to recruiting and following minority patients in clinical trials. At present, a serious impediment to recruiting non-English-speaking minorities is the lack of instruments with adequate translation. Because Spanish is the second most commonly spoken language in the United States and because persons of Hispanic origin represent approximately 10% of the population, we conducted an instrument development protocol for Spanish-speaking patients. Evaluating treatment efficacy in Spanish-speaking AD patients requires the development of assessments that are comparable to those used for English-speaking participants in clinical trials. The ADCS Instrument Development Project evaluated the sensitivity, reliability, and validity of new or improved measures in each of five assessment domains: (a) cognition (immediate and delayed memory, praxis, attention, and executive function); (b) clinical global change; (c) activities of daily living; (d) behavioral symptoms (agitation and other noncognitive symptoms); and (e) cognition in severely impaired patients. These new treatment efficacy instruments were translated for Spanish speakers and a Spanish Instrument Study was conducted in parallel with the English version of the study. This report describes instrument translation, entry criteria, and recruitment procedures. In addition, the demographic and clinical characteristics of the cohort at baseline are presented and compared to the English-speaking cohort. Implications for the development of comparably sensitive Spanish language instruments are discussed.

Aged↗

'Effective' Australian gerontology nurses: a repertory grid analysis.

Repertory grids were completed by gerontological nurses (N = 60) to elicit the personal constructs they used to characterize gerontological nurses, effective gerontological nurses and the extent to which participants believed themselves to be effective as nurses working in this specialist field. Analysis of pooled repertory grids indicated that the personal construct 'caring, compassionate, empathetic' was rated most highly as characteristic of gerontological nurses in general and of effective gerontological nurses. Cluster analysis of individual repertory grids showed no significant difference between self-perceptions of participants as effective gerontological nurses and the ideal gerontological nurses they would like to become. Other findings of this research indicate that a variety of aspects of gerontological nursing need improvement if negative perceptions of this area of nursing practice are to be altered.

Adult↗

Cisapride: a review of the evidence supporting its use in premature infants with feeding intolerance.

A systematic computerized search of all databases was performed to review the scientific evidence in support of the efficacy of cisapride in reducing feeding intolerance in premature infants. Reference lists from these articles were used to identify relevant scientific literature to address important aspects of the use of cisapride. Three open prospective, uncontrolled studies were found. All studies reported improved clinical outcomes as evidenced by decreased gastric residuals, decreased incidence of vomiting, increased feeding volume, decrease in all reflux parameters measured, and increased weight gain. These observational studies reflect the current state of knowledge and have important research and clinical implications because of the profound effects of feeding intolerance on infant growth and development and on length of stay within NICUs.

Cisapride↗

Perioperative mortality after pneumonectomy: analysis of risk factors and review of the literature.

OBJECTIVE: To determine risk factors for perioperative death associated with pneumonectomy. DESIGN: A retrospective case-control study in which a perioperative death group was compared with a survivor group, and a review of the English literature on the subject. SETTING: The Montreal General Hospital, a tertiary-care teaching institution. PATIENTS AND INTERVENTION: Ninety-two consecutive patients who underwent pneumonectomy between April 1989 and 1994. MAIN OUTCOME MEASURES: The effects of age, sex, smoking history, tumour size, type and stage, pulmonary function, cardiovascular risks, comorbidity, preoperative blood values and volume of fluids administered perioperatively. Values from the literature were reported for comparison. RESULTS: The perioperative death rate was 10.9%. Selection bias and in-hospital values reported in the literature have underestimated the death rate, with actual rates ranging from 7% to 11%. Age (odds ratio 2.48, p = 0.04), the presence of 1 or more comorbid diseases (odds ratio 7.92, p = 0.05) and amount of fluids given in the first 12 hours postoperatively (odds ratio 2.21, p = 0.06) were found to be significant risk factors for death. Multivariate logistic regression demonstrated that the volume of fluids given remains an independent risk factor whereas age and comorbid disease are dependent variables. CONCLUSIONS: The results were consistent with previously reported death rates and risk factors. Patient age and concomitant disease are not modifiable risk factors, but perioperative fluid administration and other means to prevent postpneumonectomy pulmonary edema may reduce the perioperative death rate.

Age Factors↗

High-dose chemotherapy and autologous stem cell support followed by posttransplantation doxorubicin as initial therapy for metastatic breast cancer.

High-dose chemotherapy is associated with a high complete response rate and possibly some survival advantage in patients with metastatic breast cancer. We designed a clinical trial consisting of a two-step high-dose chemotherapy regimen followed by posttransplantation doxorubicin as the first chemotherapy treatment for metastatic disease. Twenty-one patients with metastatic breast cancer and no previous chemotherapy for metastatic disease were treated with high-dose cyclophosphamide (Cy; 5000 mg/m2), followed by granulocyte colony-stimulating factor. Peripheral blood stem cells were collected. Subsequently, patients received Cy (6000 mg/m2), thiotepa (500 mg/m2), and carboplatin (800 mg/m2) (CTCb) with hematopoietic rescue. Upon recovery of hematopoietic and gastrointestinal toxicity, three cycles of doxorubicin (Dox; 60 mg/m2) were delivered. After Cy, nine patients (45%) developed neutropenic fevers. There were no episodes of bacteremia. Patients received CTCb 37 days after starting Cy and had a hospital stay of 19 days. After CTCb, the median number of days to an absolute neutrophil count >5 x 10(9)/liter was 8, and the median number of days to a platelet count >20 x 10(9)/liter was 9. Neutropenic fevers occurred in 12 patients. There were no hemorrhagic complications. Fifty-five of the 63 planned courses of Dox were delivered. The median time from peripheral blood stem cell infusion to the first Dox cycle was 38 days. The median time to the second Dox cycle was 28 days, and to the last cycle was 30 days. Three episodes of neutropenic fevers were observed. Two patients developed herpes zoster. This regimen is feasible, with acceptable toxicity.

Adult↗

The crystal structure of horse deoxyhaemoglobin trapped in the high-affinity (R) state.

Co-operative oxygen binding by the vertebrate haemoglobins arises from an equilibrium between a quaternary structure with low affinity (T), favoured in the absence of ligand, and a high affinity form (R) adopted by the fully ligated protein. While R state haemoglobin has an oxygen affinity close to that of isolated subunits, the affinity of the T state is roughly 300-fold lower. The mechanism by which the T state restrains ligand binding, and the pathway of the quaternary transition, have been largely revealed by detailed crystallographic analyses of a number of haemoglobin molecules in the equilibrium states, as well as intermediate forms of the T state including partially ligated species. The ligation intermediates of the R state, however, have not been as well characterized structurally. We report here the crystal structure of one such intermediate species, namely, horse deoxyhaemoglobin in the R state, at 1.8 A resolution. While ligand binding in the T state may result in unfavourable stereochemistry in and around the haem-ligand complex, the more plastic R structure appears to accommodate equally well both liganded and ligand-free haem. Loss of ligand at the R state haem results in movements of the haem and shifts of the FG corners, which form characteristic intersubunit contacts that distinguish the quaternary states. The shifts are comparable in magnitude to the corresponding movements associated with de-ligation in the T state, although they differ in direction. These and other differences illustrate how the structural changes in the haem pocket are communicated to the subunit interfaces and how the movements that can occur in the R state may be impeded in the T state.

Animals↗

The use of the laryngeal mask airway in recovery.

The laryngeal mask is being used increasingly both for the management of cardiorespiratory arrest and recovery after surgery. In this article, the author describes the design and development of the mask and looks at its use in recovery departments. A discussion of training issues is also included.

Contraindications↗

In vivo nitrogen metabolism in ornithine transcarbamylase deficiency.

We developed a new technique that monitors metabolic competency in female heterozygotes for ornithine transcarbamylase deficiency (OTCD). The method uses mass spectrometry to measure conversion of (15)NH4Cl to [15N]urea and [5-(15)N]glutamine following an oral load of (15)NH4Cl. We found that heterozygotes converted significantly less NH3 nitrogen to urea, with this difference being particularly obvious for symptomatic carriers, in whom the blood [15N]urea concentration (mM) was significantly less than control values at most time points. The blood concentration of [5-(15)N]-glutamine (microM) was significantly higher in both asymptomatic and symptomatic heterozygotes than it was in the control subjects. The administration of a test dose of sodium phenylbutyrate to the control group did not affect the rate of [15N]urea formation. We conclude: (a) This test effectively monitors in vivo N metabolism and might obviate the need for liver biopsy to measure enzyme activity in OTCD; (b) Asymptomatic OTCD carriers form urea at a normal rate, indicating that ureagenesis can be competent even though enzyme activity is below normal; (c) Although ostensibly asymptomatic OTCD carriers form urea at a normal rate, their nitrogen metabolism is still abnormal, as reflected in their increased production of [5-(15)N]glutamine; and (d) This new test may be important for monitoring the efficacy of novel treatments for OTCD, e.g., liver transplantation and gene therapy.

Adolescent↗

Studies on the molecular toxicology of buta-1,3-diene and isoprene epoxides.

Reactions of ethenyloxirane with amino (RNH2) and thiol (R'SH) nucleophiles occur by an SN2 mechanism involving competing ring cleavage at C-2 and C-3. In contrast, 2-ethenyl-2-methyloxirane reacts with amino (RNH2) and thiolate (R'S-) nucleophiles in methanol by regioselective SN2 attack at C-3 ("neo-pentyl" position). However, in pure water or methanol SN1 reaction occurs mainly at C-2.

Butadienes↗

Fas ligand mutation in a patient with systemic lupus erythematosus and lymphoproliferative disease.

The pathogenesis of systemic lupus erythematosus (SLE) is multifactorial and multigenetic. The apoptosis genes, fas and fas ligand (fasL), are candidate contributory genes in human SLE, as mutations of these genes result in autoimmunity in several murine models of this disease. In humans, fas mutations result in a familial autoimmune lymphoproliferative syndrome, but defects in FasL have not yet been identified. In this study, DNA from 75 patients with SLE was screened by single-stranded conformational polymorphism analysis for potential mutations of the extracellular domain of FasL. A heterozygous single-stranded conformational polymorphism for FasL, was identified in one SLE patient, who exhibited lymphadenopathy. Molecular cloning and sequencing indicated that the genomic DNA of this patient contained an 84-bp deletion within exon 4 of the fasL gene, resulting in a predicted 28 amino acid in-frame deletion. Analysis of PBMC from this patient revealed decreased FasL activity, decreased activation-induced cell death, and increased T cell proliferation after activation. This is the first report of defective FasL-mediated apoptosis related to a mutation of the human Fasl, gene in a patient with SLE and suggests that fasL mutations are an uncommon cause of the disease.

Amino Acid Sequence↗

Efficacy of treatment with the iron (III) complex of diethylenetriamine pentaacetic acid in mice and primates inoculated with live lethal dose 100 Escherichia coli.

The iron (III) complex of diethylenetriamine pentaacetic acid (DTPA iron [III]) protected mice and baboons from the lethal effects of an infusion with live LD100 Escherichia coli. In mice, optimal results were obtained when DTPA iron (III) was administered two or more hours after infection. Prevention of death occurred in spite of the fact that the adverse effects of TNF-alpha were well underway in the mouse model. The half-life of DTPA iron (III) was 51 +/- 9 min in normal baboons; primary clearance was consistent with glomerular filtration. In septic baboons, survival was observed after administration of two doses of DTPA iron (III) at 2.125 mg/kg, the first one given before, or as late as 2 h after, severe hypotension. Administration of DTPA iron (III) did not alter mean systemic arterial pressure, but did protect baboons in the presence of high levels of TNF-alpha and free radical overproduction. Furthermore, exaggerated production of nitric oxide was attenuated. The mechanism of protection with DTPA iron (III) is not obvious. Because of its ability to interact in vitro with free radicals, its poor cell permeability, and its short half-life, we postulate that DTPA iron (III) and/or its reduced form may have protected the mice and baboons by sequestration and subsequent elimination of free radicals (including nitric oxide) from their systems.

Animals↗

A randomised controlled trial comparing two schedules of antenatal visits: the antenatal care project.

OBJECTIVE: To compare the clinical and psychological effectiveness of the traditional British antenatal visit schedule (traditional care) with a reduced schedule of visits (new style care) for low risk women, together with maternal and professional satisfaction with care. DESIGN: Randomised controlled trial. SETTING: Places in south east London providing antenatal care for women receiving shared care and planning to deliver in one of three hospitals or at home. SUBJECT: 2794 women at low risk fulfilling the trial's inclusion criteria between June 1993 and July 1994. MAIN OUTCOME MEASURES: Measures of fetal and maternal morbidity, health service use, psychosocial outcomes, and maternal and professional satisfaction. RESULTS: Pregnant women allocated to new style care had fewer day admissions (0.8 v 1.0; P=0.002) and ultrasound scans (1.6 v 1.7; P=0.003) and were less often suspected of carrying fetuses that were small for gestational age (odds ratio 0.73; 95% confidence interval 0.54 to 0.99). They also had some poorer psychosocial outcomes; for example, they were more worried about fetal wellbeing antenatally and coping with the baby postnatally, and they had more negative attitudes to their babies, both in pregnancy and postnatally. These women were also more dissatisfied with the number of visits they received (odds ratio 2.50; 2.00 to 3.11). CONCLUSIONS: Patterns of antenatal care involving fewer routine visits for women at low risk may lead to reduced psychosocial effectiveness and dissatisfaction with frequency of visits. The number of antenatal day admissions and ultrasound scans performed may also be reduced. For the variables reported, the visit schedules studied are similar in their clinical effectiveness. Uncertainty remains as to the clinical effectiveness of reduced visit schedules for rare pregnancy problems.

Anxiety↗

Short-term efficacy of ultrasonically nebulized hypertonic saline in cystic fibrosis.

Progressive lung disease in patients with cystic fibrosis (CF) is caused by thick secretions, which cause airway obstruction and subsequent colonization and infection by inhaled pathogenic microorganisms. Recently, recombinant human DNase has been shown to reduce the viscoelasticity of sputum in patients with cystic fibrosis and to improve lung function. Ultrasonically nebulized hypertonic saline (HS) has been demonstrated to enhance mucociliary clearance and sputum expectoration by rehydrating airway secretions, and may therefore provide a low cost alternative. We studied the changes in pulmonary function and symptoms in a group of patients with CF who have moderate to severe lung disease. The patients were evaluated following 2 weeks of treatment with HS in an open-label study. Subjects were randomly allocated to receive 10 ml of either 0.9% NaCl (IS) or 6% NaCl (HS). Twice daily, prior to physiotherapy, treatments were delivered by a portable ultrasonic nebulizer. To prevent bronchoconstriction, 600 mg of salbutamol was administered prior to the nebulized solutions. A symptom score was recorded and spirometry was performed on day 0 before therapy was started, on day 14 (the last day of therapy), and on day 28 (14 days after the last treatment with either IS or HS). Fifty-two patients (32 males), with a mean age of 16.2 (range 7-36) years completed the study. There was no difference in baseline characteristics between the two groups. Following 2 weeks of treatment, there was a significant improvement from baseline in FEV1 of 15.0 +/- 16.0% (mean +/- SD) in patients treated with HS, compared with a change of 2.8 +/- 13% in those on IS therapy (P = 0.004). Furthermore, there was a subjective improvement in the effectiveness of chest physiotherapy as reported by those using HS (P = 0.02). The treatment was well tolerated. We conclude that in patients with CF, ultrasonically nebulized hypertonic saline improves lung function in a way similar to that reported for human recombinant DNase when inhaled over a 2 week period. Nebulized saline also enhances the perception of effectiveness of chest physiotherapy.

Administration, Inhalation↗