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Biomedical subjects

J Ashley

Publications and source records attributed to J Ashley.

At least 19 recordsLinked to original sources
PubMed2001

Breakthrough cancer pain: a randomized trial comparing oral transmucosal fentanyl citrate (OTFC) and morphine sulfate immediate release (MSIR).

Oral transmucosal fentanyl citrate (OTFC); Actiq) is a drug delivery formulation used for management of breakthrough cancer pain. Previous studies with open-label comparisons indicated OTFC was more effective than patients' usual opioid for breakthrough pain. The objective of this study was to compare OTFC and morphine sulfate immediate release (MSIR) for management of breakthrough pain in patients receiving a fixed scheduled opioid regimen. This double-blind, double-dummy, randomized, multiple crossover study was conducted at 19 US university- and community-based hospitals and clinics and comprised 134 adult ambulatory cancer patients. Patients were receiving a fixed scheduled opioid regimen equivalent to 60-1000 mg/day oral morphine or 50-300 microg/h transdermal fentanyl, were using a 'successful' MSIR dose (15-60 mg) as defined by entry criteria, and were experiencing 1-4 episodes of breakthrough pain per day. In open-label fashion, OTFC was titrated such that a single unit (200-1600 microg) provided adequate pain relief with acceptable side effects. Successfully titrated patients entered the double-blind phase of the study and received ten prenumbered sets of randomized capsules and oral transmucosal units. Five sets were the successful OTFC dose paired with placebo capsules, and five sets were placebo OTFC paired with capsules containing the successful MSIR dose. Patients took one set of study medication for each episode of target breakthrough pain. Pain intensity (PI), pain relief (PR) and global performance of medication (GP) scores were recorded. Pain intensity differences (PID) were calculated and 15-min PID was the primary efficacy variable. Adverse events were recorded. Sixty-nine percent of patients (93/134) found a successful dose of OTFC. OTFC yielded outcomes (PI, PID, and PR) at all time points that were significantly better than MSIR. GP also favored OTFC and more patients opted to continue with OTFC than MSIR following the study. Somnolence, nausea, constipation, and dizziness were the most common drug-associated side effects. In conclusion, OTFC was more effective than MSIR in treating breakthrough cancer pain.

Administration, Oral↗
PubMed2000

Diet controversies in lipid therapy.

Increasing awareness of the relationship between diet and disease has prompted a notable increase in nutrition research. The focus of many of these studies continues to be on amount and type of fat in the diet. At the same time, a great deal of attention is being directed at other dietary components and their mode of action. The results are promising. More definitive answers must await future clinical trial data. However, the total dietary approach, including compliance measures, remains the foundation on which other nutrition recommendations should be based.

Antioxidants↗
PubMed1999

Cyclosporine plasma unbound fraction in heart and lung transplantation recipients.

To investigate the variability in the unbound fraction (fu) of cyclosporine in recipients of heart, heart-lung, and lung transplantation, cyclosporine fu was determined ex vivo in plasma by equilibrium dialysis. In a retrospective study, 260 samples of plasma (one to seven per patient) were obtained from 89 heart (86%), lung (9%), and heart-lung (5%) transplant patients. The unbound fraction (x100) of cyclosporine ranged from 0.52% to 3.94%, with an overall mean of 1.53%+/-0.375% (SD). The mean percentage unbound for individual patients ranged from 0.71% to 1.98%, giving a 2.8-fold interpatient variation. In heart transplant recipients (66 patients), the values of fu were significantly lower (p < 0.01) during more severe rejection episodes, which required antirejection treatment (endomycardial biopsy result of grade 3a and higher) than in the absence of rejection (grade 0) or during grade la rejections. The value of fu did not vary with organ transplanted (p = 0.35) or etiology of organ failure (p = 0.32). Cyclosporine fu was negatively correlated with the age of the patient (r = -0.18, p < 0.05). Correlations were not observed between fu and blood biochemical and cytologic indices. However, fu was significantly lower (p < 0.01) in hypercholesterolemic transplant recipients (1.37+/-0.52%) than in normocholesterolemic patients (1.60+/-0.63%). Administration of simvastatin resulted in a significant increase in the mean fu from 1.40+/-0.09%) to 1.82+/-0.13% (paired t test, n = 13; p < 0.01). In patients who received ketoconazole, fu was not different from controls. These findings suggest that the level of cyclosporine fu may be an important determinant of immunosuppressive activity of cyclosporine. Moreover, the variation in fu could be strongly related to the concentration of serum lipoproteins; interpretation of the results of cyclosporine monitoring thus requires consideration of the lipidemic status of the patient.

Adolescent↗
PubMed1999

Evaluation of Simulated Presence: a personalized approach to enhance well-being in persons with Alzheimer's disease.

OBJECTIVE: To evaluate the efficacy of Simulated Presence, a personalized approach to enhance well-being among nursing home residents with Alzheimer's disease and related dementia's (ADRD). DESIGN: Latin-Square, double blinded, 3-factor design with restrictive randomization of three treatments (the study intervention, a placebo audio tape of a person reading the newspaper, and usual care). The three factors were treatment, time, and facility type. SETTING: Nine nursing homes in Eastern Massachusetts and Southern New Hampshire. PARTICIPANTS: Fifty-four subjects with documented ADRD who were aged 50 years or older, medically stable, had resided in their current nursing home for at least 3 months, and who had no planned discharge. All subjects had a history of agitated or withdrawn behaviors. INTERVENTION: The purpose of Simulated Presence is to provide a personalized intervention for persons with moderate to severe cognitive impairment. Through a unique testing process, some of the best loved memories of the ADRD person's lifetime are identified and then those memories are introduced to the patient in the format of a telephone conversation using a continuous play audio tape system. The intervention may be used for extended periods of time because each repetition is viewed as a fresh, live telephone call as a result of the short-term memory deficit of the person with ADRD. MEASUREMENTS: Direct observations of outcomes included using a newly developed scale, the Scale for the Observation of Agitation in Persons with Dementia, an agitation visual analog scale, the Positive Affect Rating Scale (mood and "interest"), a withdrawal visual analog scale, and facial diagrams of mood. Reported measures included daily staff observation logs of responses to interventions offered, and weekly staff surveys using the short-form Cohen-Mansfield Agitation Inventory and the Multidimensional Observation Scale for Elderly Subjects (mood and "interest"). Severity of dementia was assessed by the Mini-Mental State Exam, the Test for Severe Impairment, the Bedford Alzheimer's Nursing Scale, and the ADL Self-Performance Scale. RESULTS: Chi-square analysis of direct observations, using facial diagrams, revealed that Simulated Presence was equivalent to usual care (P = .141) and superior to placebo for producing a happy facial expression (P = .001). A positive effect was also documented in nursing staff observation logs using Analysis of Variance techniques (ANOVA) for subjects during Simulated Presence phases compared with the placebo phases (P < .001) and usual care phases (P < .001). According to ANOVA analyses of "interest" from weekly surveys, Simulated Presence was superior to both usual care (P = .001) and placebo (P = .008). We were unable to find evidence of significant differences (P < .05) among interventions for other direct observations and weekly reports of overall agitation or mood aspects of withdrawal. Subjects accepted the intervention most of the time, except for five subjects who refused it more than 50% of the time. CONCLUSION: This study provided evidence that Simulated Presence can be effective in enhancing well-being and decreasing problem behaviors in the nursing home setting as a substitute for or complement to usual care.

Aged↗
PubMed1998

Inactivating mutations in an SH2 domain-encoding gene in X-linked lymphoproliferative syndrome.

X-linked lymphoproliferative syndrome (XLP) is an inherited immunodeficiency characterized by increased susceptibility to Epstein-Barr virus (EBV). In affected males, primary EBV infection leads to the uncontrolled proliferation of virus-containing B cells and reactive cytotoxic T cells, often culminating in the development of high-grade lymphoma. The XLP gene has been mapped to chromosome band Xq25 through linkage analysis and the discovery of patients harboring large constitutional genomic deletions. We describe here the presence of small deletions and intragenic mutations that specifically disrupt a gene named DSHP in 6 of 10 unrelated patients with XLP. This gene encodes a predicted protein of 128 amino acids composing a single SH2 domain with extensive homology to the SH2 domain of SHIP, an inositol polyphosphate 5-phosphatase that functions as a negative regulator of lymphocyte activation. DSHP is expressed in transformed T cell lines and is induced following in vitro activation of peripheral blood T lymphocytes. Expression of DSHP is restricted in vivo to lymphoid tissues, and RNA in situ hybridization demonstrates DSHP expression in activated T and B cell regions of reactive lymph nodes and in both T and B cell neoplasms. These observations confirm the identity of DSHP as the gene responsible for XLP, and suggest a role in the regulation of lymphocyte activation and proliferation. Induction of DSHP may sustain the immune response by interfering with SHIP-mediated inhibition of lymphocyte activation, while its inactivation in XLP patients results in a selective immunodeficiency to EBV.

Amino Acid Sequence↗
PubMed1998

Effect of exercise induced hypoxaemia on myocardial repolarisation in severe chronic obstructive pulmonary disease.

BACKGROUND: Exercise training is being promoted increasingly for patients with chronic obstructive pulmonary disease (COPD). Many of these patients experience exercise related arterial desaturation but the clinical importance of these hypoxaemic episodes is not known. QTc dispersion is a marker of myocardial repolarisation abnormalities and there has been much interest in its role as a non-invasive predictor of cardiac arrhythmias and sudden death. However, little is known about the dynamic effects that exercise and hypoxaemia have on QTc dispersion in patients with COPD. METHODS: 20 patients with severe COPD (FEV1 < 40% predicted) undertook two 15 minute treadmill tests at a speed calculated to produce a constant workload of 50% maximum oxygen consumption (VO2max) during which they were blindly given either air or 35% oxygen in random order. Physiological measurements taken throughout exercise included 12 lead electrocardiograms from which QTc dispersion values were calculated according to standard criteria. Nine of the patients who desaturated with exercise were studied further. A similar degree of hypoxaemia was induced at rest by giving them a titrated mixture of air and oxygen and the changes in QTc dispersion were recorded. RESULTS: 11 of the 20 patients developed significant hypoxaemia (desaturation by > or = 5% to < 90%) with exercise breathing air. There were no significant changes in QTc dispersion with either exercise or hypoxaemia. There were no significant changes in QTc dispersion when comparing those who did and did not desaturate, and those with and without a high baseline QTc dispersion values (60 ms). Induced hypoxaemia without exercise also failed to worsen QTc dispersion. CONCLUSIONS: No evidence was found to suggest that exercise, even when associated with hypoxaemia, causes myocardial repolarisation abnormalities in patients with COPD.

Aged↗
PubMed1997

Cosmid contig and transcriptional map of three regions of human chromosome 21q22: identification of 37 novel transcripts by direct selection.

Human chromosome 21 is associated with many disorders, including Down syndrome (DS). In an effort to identify genes involved in brain development or function and therefore implicated in the mental retardation associated with DS, we chose YACs from three regions of chromosome 21: a region within the so-called "Down syndrome critical region," a region proximal to it, and one distal to it. We made cosmid libraries from these YACs and generated high-resolution physical maps by constructing cosmid contigs. These are the first cosmid contigs on chromosome 21 outside the critical region. The cosmids were used for direct selection of cDNAs to isolate chromosome 21 expressed sequences. We have isolated 45 nonredundant partial cDNAs and mapped these back to the cosmid contigs. We isolated 3 nonoverlapping portions of DSCR1 and a part of GIRK2 and identified 3 nonoverlapping partial cDNAs with similarity to the rat Dyrk gene, which turned out to be the human homologue (MNB) of the Drosophila minibrain gene. Twelve sequences had matches with either STS or EST entries in the databases, including a chromosome 21 EST, a chromosome 21 STS, and 6 unmapped expressed sequence entries. Only 1 sequence resulted in a match with a protein entry. The remaining 25 sequences revealed no similarity to any database entry. All of these partial cDNAs are expressed as determined by Northern blotting or by RT-PCR.

Animals↗
PubMed1997

New gene for autosomal recessive non-syndromic hearing loss maps to either chromosome 3q or 19p.

Autosomal recessive non-syndromic hearing loss (ARNSHL) is the most common form of prelingual inherited hearing impairment. A small consanguineous family with this disorder was ascertained through the Institute of Basic Medical Sciences in Madras, India. Conditions such as rubella, prematurity, drug use during pregnancy, perinatal trauma, and meningitis were eliminated by history. Audiometry was performed to confirm severe-to-profound hearing impairment in affected persons. After excluding linkage to known DFNB genes, two genomic DNA pools, one from the affected persons and the other from their non-affected siblings and the parents, were used to screen 165 polymorphic markers evenly spaced across the autosomal human genome. Two regions showing homozygosity-by-descent in the affected siblings were identified on chromosomes 3q21.3-q25.2 and 19p13.3-p13.1, identifying one (or possibly both) as the site of a novel ARNSHL gene.

Algorithms↗
PubMed1996

A human homologue of Drosophila minibrain (MNB) is expressed in the neuronal regions affected in Down syndrome and maps to the critical region.

The minibrain (mnb) gene of Drosophila melanogaster encodes a serine-threonine protein kinase with an essential role in postembryonic neurogenesis. A corresponding human gene with similar function to mnb could provide important insights into both normal brain development and the abnormal brain development and mental retardation observed in many congenital disorders. Trisomy 21 or Down syndrome (DS) is the most frequent human birth defect. It is associated with mental retardation and a broad spectrum of physical abnormalities. A region on human chromosome 21 has been designated the Down syndrome critical region (DSCR) and when present in three copies, this is responsible for many of the characteristic features of DS, including mental retardation. We have isolated a human homologue of mnb from the DSCR. MNB encodes a 6.1 kb transcript which is expressed in foetal brain, lung, kidney and liver. Using a human probe, two major transcripts (6.1 and 3.1 kb) were identified in mouse and expression was detected in situ in several regions of the mouse brain, including the olfactory bulb, the cerebellum, the cerebral cortex, the pyramidal cell layer of the hippocampus and several hypothalamic nuclei. This expression pattern corresponds to the regions of the brain that are abnormal in individuals with DS and suggests that overexpression of MNB could have detrimental consequences in DS patients.

Amino Acid Sequence↗
PubMed1994

Study groups: are they effective in preparing students for NCLEX-RN?

The effectiveness of faculty-directed study groups as an intervention to prepare nurse candidates for NCLEX-RN was evaluated. The NCLEX-RN performance of a baccalaureate class who had participated in study groups was compared to the performance of a prior class who had not participated in study groups. Academic subgroups within the classes were compared to determine if study groups were equally effective across levels of academic achievement. The possible reasons for the significant difference in the NCLEX-RN passing rate between "at-risk" students who participated in study groups and at-risk students who did not participate in study groups are discussed. Discussion also considers possible factors influencing the generally better performance of study group participants at all academic levels. Suggestions for future intervention research direct attention to time intensity of interventions and research control through random assignments to treatment groups.

Adult↗
PubMed1993

Prophylactic paracetamol for analgesia after vaginal termination of pregnancy.

Many patients present to day surgery clinics for vaginal termination of pregnancy, a procedure which is frequently complicated by postoperative abdominal pain. We have assessed the efficacy of prophylactic paracetamol 1000 mg given orally shortly before surgery in 834 such patients in a randomised, placebo-controlled, double-blind study. Postoperative pain was reported in 35% of patients, with no significant difference between treated and control patients. This negative finding was unexpected and is so far unexplained, given the usual efficacy of oral paracetamol in relieving this type of pain after it has occurred.

Abortion, Induced↗
PubMed1993

Towards optimal analgesia after caesarean section: comparison of epidural and intravenous patient-controlled opioid analgesia.

The provision of optimal analgesia after caesarean section remains a challenge as satisfactory pain relief must be combined with patient satisfaction, including the ability to care for the newborn. In a prospective study of 132 patients, we have compared epidural analgesia with intravenous patient-controlled analgesia (IVPCA) after either epidural or general anaesthesia. Different bolus doses of opioid (pethidine 10 mg and 20 mg) in the IVPCA group were also compared. Although epidural morphine provided the greatest efficacy (average pain score out of 10 was 1.8 v. 2.9-3.4 for the other groups), IVPCA, especially with a bolus dose of 20 mg, and especially after epidural anaesthesia, provided the greatest patient satisfaction with the least side-effects.

Analgesia, Epidural↗
PubMed1993

Towards optimal analgesia after caesarean section: comparison of epidural and intravenous patient-controlled opioid analgesia.

The provision of optimal analgesia after caesarean section remains a challenge as satisfactory pain relief must be combined with patient satisfaction, including the ability to care for the newborn. In a prospective study of 132 patients, we have compared epidural analgesia with intravenous patient-controlled analgesia (IVPCA) after either epidural or general anaesthesia. Different bolus doses of opioid (pethidine 10 mg and 20 mg) in the IVPCA group were also compared. Although epidural morphine provided the greatest efficacy (average pain score out of 10 was 1.8 v. 2.9-3.4 for the other groups), IVPCA, especially with a bolus dose of 20 mg, and especially after epidural anaesthesia, provided the greatest patient satisfaction with the least side-effects.

Analgesia, Epidural↗
PubMed1992

Comparison of epidural and intravenous opioid analgesia after elective caesarean section.

Patient acceptance is a particularly relevant method of assessing currently employed epidural and intravenous techniques of opioid analgesia after elective caesarean section. We have prospectively studied 71 such patients, randomised postoperatively to receive epidural morphine, intravenous morphine or intravenous pethidine. When compared with either intravenous opioid, epidural morphine provided twofold better average or excellent analgesia with 30% less drowsiness but with about 50% more pruritus. In spite of this troublesome complication, more patients (83% vs 74%) preferred epidural to intravenous opioid analgesia.

Analgesia, Epidural↗
PubMed1991

The effectiveness of an intervention to promote successful performance on NCLEX-RN for baccalaureate students at risk for failure.

This study evaluated the effectiveness of an intervention designed to enhance the performance of high-risk baccalaureate students on the National Council Licensure Examination for Registered Nurses (NCLEX-RN). Thirty senior nursing students met risk criteria drawn from the NCLEX-RN prediction literature: a nursing grade point average (GPA) of 2.40 or below, a ranking on the Mosby Assesstest at or below the 20th percentile, and/or a diagnosed learning disability. Fourteen students in this nonrandomized, posttest-only study received the intervention. Sixteen students served as a control group. The groups were equivalent on 12 academic variables prior to treatment. Concepts of test-wiseness and test-coaching served as the basis for the intervention. The NCLEX-RN passing rate for the group participating in the intervention was 92.9% compared to 50% for the control group. The findings of this study provide preliminary evidence that a long-term intervention can assist high-risk students in passing the NCLEX-RN.

Adult↗