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Biomedical subjects

C Davis

Publications and source records attributed to C Davis.

At least 37 records · Page 2Linked to original sources
PubMed2001

Strategies to manage the adverse effects of oral morphine: an evidence-based report.

Successful pain management with opioids requires that adequate analgesia be achieved without excessive adverse effects. By these criteria, a substantial minority of patients treated with oral morphine (10% to 30%) do not have a successful outcome because of (1) excessive adverse effects, (2) inadequate analgesia, or (3) a combination of both excessive adverse effects along with inadequate analgesia. The management of excessive adverse effects remains a major clinical challenge. Multiple approaches have been described to address this problem. The clinical challenge of selecting the best option is enhanced by the lack of definitive, evidence-based comparative data. Indeed, this aspect of opioid therapeutics has become a focus of substantial controversy. This study presents evidence-based recommendations for clinical-practice formulated by an Expert Working Group of the European Association of Palliative Care (EAPC) Research NETWORK: These recommendations highlight the need for careful evaluation to distinguish between morphine adverse effects from comorbidity, dehydration, or drug interactions, and initial consideration of dose reduction (possibly by the addition of a co analgesic). If side effects persist, the clinician should consider options of symptomatic management of the adverse effect, opioid rotation, or switching route of systemic administration. The approaches are described and guidelines are provided to aid in selecting between therapeutic options.

Administration, Oral↗
PubMed2001

Rising pp65 antigenemia during preemptive anticytomegalovirus therapy after allogeneic hematopoietic stem cell transplantation: risk factors, correlation with DNA load, and outcomes.

To determine the risk factors and outcomes associated with rising cytomegalovirus (CMV) antigenemia levels during preemptive therapy among stem cell allograft recipients, 119 patients with CMV antigenemia were studied. Patients were prospectively monitored for CMV antigenemia weekly; those with positive findings on antigenemia tests were treated with intravenous ganciclovir (5 mg/kg twice daily for 1 week, followed by 5 mg/kg per day for 5-6 d/wk). While on therapy, 47 of 119 (39%) patients demonstrated increases that were 2 or more times greater than their baseline values, whereas 33 of 119 (28%) patients demonstrated increases that were 5 or more times greater. Rising antigenemia was confirmed by polymerase chain reaction for CMV DNA. Multivariate analysis identified corticosteroids as the primary risk factor for increasing antigenemia: for increases greater than or equal to twice the baseline, 1 to 2 mg/kg steroids was associated with an odds ratio (OR) of 4.0. For increases greater than or equal to 2 mg/kg steroids, the OR was 10.1. CMV isolates obtained at the time of rising antigenemia were susceptible to ganciclovir, indicating that resistance was not a major factor. Overall, rising antigenemia levels were not correlated with CMV disease. All 4 patients in whom CMV disease developed during therapy, however, had rising antigenemia levels. Among the 47 patients with antigenemia increases greater than or equal to twice the baseline, 15 were re-induced with antivirals, whereas 32 continued to receive maintenance therapy. All 4 patients in whom CMV disease developed during therapy received maintenance therapy, and 3 died with CMV disease. Thus, host factors such as the receipt of corticosteroids explain increasing viral load during the early phase of preemptive therapy. Continued induction dosing or re-induction may protect against early breakthrough CMV disease and CMV-related death among patients with rising antigenemia on preemptive therapy. (Blood. 2001;97:867-874)

Adolescent↗
PubMed2001

Preoperative chemoradiotherapy and radical surgery for locally advanced distal rectal adenocarcinoma: pathologic findings and clinical implications.

PURPOSE: Preoperative chemoradiotherapy followed by radical surgical resection has been the preferred treatment for patients presenting with locally advanced distal rectal carcinoma at our institutions. We postulated that chemoradiotherapy-induced pathologic response of the primary tumor would identify which patients would be candidates for local excision as definitive surgical therapy. METHODS: A retrospective analysis of 60 patients with palpable, locally advanced, distal rectal adenocarcinomas treated from 1995 to 2000 was performed. All patients received preoperative chemoradiotherapy consisting of 5-fluorouracil (325 mg/m(2)) and leucovorin (20 mg/m(2)) by bolus infusion on Days 1 through 5 and 29 through 33 delivered concurrently with at least 45.0 to 50.4 Gy of pelvic radiation, followed six to eight weeks later by radical surgery and then adjuvant chemotherapy. RESULTS: Among 60 patients (20 females) there was a mean age of 58.7 (28-84) years. Clinical staging was as follows: Stage II, 14 patients (23 percent); Stage III, 35 patients (58 percent); and Stage IV, 11 patients (18 percent). Pathologic examination revealed that negative margins were obtained in 58 patients (97 percent). Downstaging to T0-2N0 was achieved in 17 patients (28 percent), with five (8 percent) achieving a pathologically complete response. Lymph nodes were positive in 24 patients (40 percent) despite chemoradiotherapy. Pathologic node positivity was found in 0 of 5 pT0 patients, 9 (41 percent) of 22 pT1 or pT2, and 15 (45 percent) of 33 pT3. Clinical stage, tumor size, pathologic stage, and adverse histologic features could not reliably predict pN0 status, except pT0 (5 patients only). CONCLUSIONS: Preoperative chemoradiotherapy often downsizes and downstages locally advanced rectal carcinoma. Neither pretreatment clinical characteristics, response to preoperative chemoradiotherapy, or pathologic features reliably predict pN0 status. Therefore, local excision is not recommended as an alternative to radical surgery for locally advanced adenocarcinoma of the distal rectum regardless of the response of the primary tumor to preoperative chemoradiotherapy.

Adenocarcinoma↗
PubMed2001

Lapses of concentration and dyslexic performance on the Ternus task.

Recently, Cestnick and Coltheart (Cognition 71 (1999) 231) have reported evidence of abnormal performance on the Ternus apparent motion task in dyslexics. We demonstrate that some aspects of their data may be accounted for by more frequent lapses of concentration in the dyslexic group than in controls. We then report on a study in which a modification of the Ternus procedure was employed to simplify the task and to control for the effects of inattention. The results suggest that dyslexics do genuinely differ from normal readers in their perceptual processing.

Attention↗
PubMed2001

An international collaborative study to establish the 1st international standard for HIV-1 RNA for use in nucleic acid-based techniques.

Twenty-six laboratories from 10 different countries participated in a collaborative study to establish the 1st International Standard for HIV-1 RNA for use in nucleic acid-based techniques (NAT). Three candidate preparations were tested all based on genotype B viruses. The candidates were tested by each laboratory at a range of dilutions in four independent assays and the results collated and analysed statistically. All three candidates gave results that were tightly grouped, with little difference between the results from different laboratories or from the use of different assays. Studies of relative potency showed good agreement between laboratories. There were no significant differences between five commercial assay types, except that candidate XX showed a slightly lower potency compared to YY and ZZ with a single commercial assay. The reason for this was not established. Degradation studies showed that the freeze-dried preparations were stable at -20,4 and 20 degrees C for 26 weeks, the longest period studied, but that they became difficult to reconstitute after 3 weeks at 45 degrees C and 9 weeks at 37 degrees C. As a result of the study, the World Health Organisation (WHO) Expert Committee on Biological Standardisation (ECBS) established the preparation referred to as candidate YY (NIBSC Code No. 97/656) as the 1st International Standard for HIV-1 RNA for use with NAT with an assigned potency of 100000 International Units per vial.

HIV Infections↗
PubMed2001

Double-blind randomized phase II study of hyperbaric oxygen in patients with radiation-induced brachial plexopathy.

BACKGROUND: Radiation-induced brachial plexopathy (RIBP) is an untreatable complication of curative radiotherapy for early breast cancer, characterized by chronic neuropathic pain and limb paralysis. Hyperbaric oxygen (HBO2) therapy is known to promote healing of tissue rendered ischaemic by radiotherapy, but is untested in RIBP. METHODS: Thirty four eligible research volunteers suffering from RIBP were randomized to HBO2 or control group. The HBO2 group breathed 100% oxygen for 100 min in a multiplace hyperbaric chamber on 30 occasions over a period of 6 weeks. The control group accompanied the HBO2 group and breathed a gas mixture equivalent to breathing 100% oxygen at surface pressure. All volunteers and investigators, except the operators of the hyperbaric chamber and the trial statistician, were blind to treatment assignments. The warm sensory threshold, which measures the function of small sensory fibres, was selected as the primary endpoint. FINDINGS: Pre-treatment neurophysiological tests were grossly abnormal in the affected hand compared to the unaffected hand in both HBO2 and control groups, as expected, but no statistically significant differences were noted in either group at any time up to 12 months post-treatment. However, normalization of the warm sensory threshold in two of the HBO2 group was reliably recorded. Two cases with marked chronic arm lymphoedema reported major and persistent improvements in arm volume for at least 12 months after treatment with HBO2. IINTERPRETATION: There is no reliable evidence to support the hypothesis that HBO2 therapy slows or reverses RIBP in a substantial proportion of affected individuals, although improvements in warm sensory threshold offer some suggestion of therapeutic effect. Improvement in long-standing arm lymphoedema was not anticipated, and justifies further investigation.

Action Potentials↗
PubMed2001

Cardiovascular (CV) responsivity and recovery to acute stress and future CV functioning in youth with family histories of CV disease: a 4-year longitudinal study.

Blood pressure (BP) and heart rate (HR) data obtained during supine rest, in response to and recovery from four laboratory stressors in a baseline year were used to predict supine resting BP and HR values obtained during each of four consecutive annual follow-up evaluations. Subjects were 385 normotensive youth [95 African American (AA) males, 106 AA females, 92 European American (EA) males, 92 EA females] (mean age 12.7+/-2.6 at baseline year) with a positive family history of cardiovascular disease (CVD). During the baseline evaluation subjects were presented with four laboratory stressors (namely, postural change, video game challenge, social competence interview, and parent--child conflict discussion). The BP and HR values taken during each of the laboratory stressors and during the post stressor recovery periods were converted to z-scores which were averaged to yield aggregate measures for systolic and diastolic BP and HR responsivity and recovery. The data obtained during the baseline evaluation were subsequently used to predict the follow-up values of supine resting BP and HR. The prediction models were fairly consistent across each of the 4 follow-up years. Responsivity or recovery accounted for up to 6% of the total variance after accounting for baseline values. Within the prediction models responsivity or recovery accounted for 4--56% of the variance. The predictive value of the derived models did not decline from one annual evaluation to the next over the length of the study. CV recovery may supplement resting and responsivity in the prediction of future development of CVD

Adolescent↗
PubMed2001

Long-term observations of patients receiving transdermal fentanyl after a randomized trial.

We observed 73 cancer patients receiving transdermal fentanyl for 1-29 (mean 5.5) months immediately after participation in a randomized clinical trial. Of these, 32 received fentanyl until death, 18 were lost to follow-up, 11 required alternative analgesia, and 12 withdrew for other reasons. The median first recorded dose (not necessarily the patient's first fentanyl dose) was 75 microg/h. The median final dose was 100 microg/h. All but 3 patients required <300 microg fentanyl/h. In the 16 who received fentanyl for > or =3 months until death, the median dose was unchanged (100 microg/h) 3 months before death and at death; 8/16 required no dosage change. The incidence of constipation, skin reactions, nausea, and vomiting was low. No significant respiratory depression was associated with fentanyl. Most patients (85%) and investigators (86%) rated the treatment as good or excellent. We conclude that long-term treatment with transdermal fentanyl is safe and acceptable to many cancer patients.

Administration, Cutaneous↗
PubMed2001

Quality improvement in chronic illness care: a collaborative approach.

BACKGROUND: Despite rapid advances in the clinical and psycho-educational management of diabetes, the quality of care received by the average patient with diabetes remains lackluster. The "collaborative" approach--the Breakthrough Series (BTS; Institute for Healthcare Improvement [IHI]; Boston)--coupled with a Chronic Care Model was used in an effort to improve clinical care of diabetes in 26 health care organizations. METHODS: Descriptive and pre-post data are presented from 23 health care organizations participating in the 13-month (August 1998-September 1999) BTS to improve diabetes care. The BTS combined the system changes suggested by the chronic care model, rapid cycle improvement, and evidence-based clinical content to assist teams with change efforts. The characteristics of organizations participating in the diabetes BTS, the collaborative process and content, and results of system-level changes are described. RESULTS: Twenty-three of 26 teams completed participation. Both chart review and self-report data on care processes and clinical outcomes suggested improvement based on changes teams made in the collaborative. Many of the organizations evidencing the largest improvements were community health centers, which had the fewest resources and the most challenged populations. DISCUSSION: The initial Chronic Illness BTS was sufficiently encouraging that replication and evaluation of the BTS collaborative model is being conducted in more than 50 health care systems for diabetes, congestive heart failure, depression, and asthma. This model represents a feasible method of improving the quality of care across different health care organizations and across multiple chronic illnesses.

Aged↗
PubMed2001

Novel enzyme activities and functional plasticity revealed by recombining highly homologous enzymes.

BACKGROUND: Directed evolution by DNA shuffling has been used to modify physical and catalytic properties of biological systems. We have shuffled two highly homologous triazine hydrolases and conducted an exploration of the substrate specificities of the resulting enzymes to acquire a better understanding of the possible distributions of novel functions in sequence space. RESULTS: Both parental enzymes and a library of 1600 variant triazine hydrolases were screened against a synthetic library of 15 triazines. The shuffled library contained enzymes with up to 150-fold greater transformation rates than either parent. It also contained enzymes that hydrolyzed five of eight triazines that were not substrates for either starting enzyme. CONCLUSIONS: Permutation of nine amino acid differences resulted in a set of enzymes with surprisingly diverse patterns of reactions catalyzed. The functional richness of this small area of sequence space may aid our understanding of both natural and artificial evolution.

Aminohydrolases↗
PubMed2001

Expression profiling using microarrays fabricated by an ink-jet oligonucleotide synthesizer.

We describe a flexible system for gene expression profiling using arrays of tens of thousands of oligonucleotides synthesized in situ by an ink-jet printing method employing standard phosphoramidite chemistry. We have characterized the dependence of hybridization specificity and sensitivity on parameters including oligonucleotide length, hybridization stringency, sequence identity, sample abundance, and sample preparation method. We find that 60-mer oligonucleotides reliably detect transcript ratios at one copy per cell in complex biological samples, and that ink-jet arrays are compatible with several different sample amplification and labeling techniques. Furthermore, results using only a single carefully selected oligonucleotide per gene correlate closely with those obtained using complementary DNA (cDNA) arrays. Most of the genes for which measurements differ are members of gene families that can only be distinguished by oligonucleotides. Because different oligonucleotide sequences can be specified for each array, we anticipate that ink-jet oligonucleotide array technology will be useful in a wide variety of DNA microarray applications.

Cells, Cultured↗
PubMed2001

Thinness and body shape of Playboy centerfolds from 1978 to 1998.

OBJECTIVE: Changes in the body weight and shape of Playboy centerfolds over the past two decades (1978-1998) were examined. METHODS: The body mass index (BMI) and waist-to-hip circumference ratio (WHR) were obtained from measurements reported by 240 centerfolds (ages 19-35 y). RESULTS: The 20-y averages (mean+/-s.d.) were 18.1+/-0.8 kg/m2 for BMI and 0.68+/-0.03 for WHR, and there has been no appreciable change in either BMI or WHR in centerfolds over the past 20 y. Based on current recommendations for the classification of underweight (BMI<18.5 kg/m2), 70% of the centerfolds were underweight. Further, 77.5% of the centerfolds were <85% of their ideal body weight. CONCLUSION: Given the perception of Playboy centerfolds as culturally 'ideal' women, the notion that 70% of them are underweight highlights the social pressures on women to be thin and helps to explain the high levels of body dissatisfaction and disordered eating among women.

Adult↗
PubMed2001

Evaluating the effectiveness of advocacy training for breast cancer advocates in Australia.

There is growing trend in health care for patients and consumers to have an active voice in all decisions related to their care. The purpose of the current study was to assess the effectiveness of an advocacy training programme for breast cancer consumers in Australia. The participants included 51 women who attended a 3-day advocacy training programme in three different states across Australia. Participants completed a pre- and post-questionnaire at 6 months follow-up to assess their involvement in breast cancer advocacy activities and organizations. Findings revealed a significant increase in participants' involvement in serving as a member of a board or committee, working on clinical trials recruitment issues, working on patient resources, and involvement in breast cancer advocacy groups after completing the training programme. However, no change was found in other key advocacy areas, such as, lobbying for change or reviewing research protocols. Implications for future advocacy training programmes and research were discussed.

Australia↗
PubMed2001

The microsatellites of Escherichia coli: rapidly evolving repetitive DNAs in a non-pathogenic prokaryote.

We have demonstrated hypervariability of native short-motif repeats (microsatellites) in Escherichia coli. Twenty-five of the longest microsatellites in the E. coli genome were identified. These were analysed for length variability among 22 wild-type (non-mutator) isolates from the E. coli collection of reference (ECOR). Non-coding mononucleotide repeats are consistently polymorphic among these genetically diverse E. coli. Length differences in variable microsatellites allowed all E. coli strains examined to be uniquely differentiated. Phylogenetic analysis of the variable repeats shows ubiquitous homoplasy at the level of divergence represented by the sample set, suggesting that these markers are hypermutable and should prove valuable for the discrimination of closely related strains that are not otherwise genetically differentiable. Genomic analyses suggest that similar markers are also likely to be found in all other prokaryotes.

Biological Evolution↗
PubMed2001

Development of multiplexed nucleic acid testing for human immunodeficiency virus type 1 and hepatitis C virus.

BACKGROUND AND OBJECTIVES: In most Western countries, blood donations are routinely screened for hepatitis C virus (HCV) RNA by polymerase chain reaction (PCR) or other nucleic acid tests. We describe the development of a multiplexed assay for human immunodeficiency virus type 1 (HIV-1) and HCV in an internally controlled PCR suitable for large-scale blood donor screening. MATERIALS AND METHODS: The HIV/HCV multiplexed PCR used primers from highly conserved regions in the long terminal repeat region. The National Institute for Biological Standards and Controls (NIBSC) International HIV-1 RNA standard, run control and HIV-1 subtype panel were used for assay evaluation. RESULTS: The HIV-1 PCR showed a sensitivity of 24 IU/ml for HIV-1 RNA (a dilution where 95% of replicate reactions were positive), which was at least five times more sensitive than the Roche Monitor version 1.5 (using the ultrasensitive extraction protocol) and Organon NASBA assays. The assay was capable of detecting all subtypes of HIV-1 (A to H), as well as the more divergent group N and O variants. The sensitivity of the PCR was unaffected by multiplexing with HCV primers and by the presence of a bovine viral diarrhoea virus (BVDV) internal control. CONCLUSION: We have developed a highly sensitive multiplexed PCR for HIV-1 and HCV RNA screening that can be introduced into current PCR-based blood donor screening at minimal cost and without significant operational changes.

Conserved Sequence↗
PubMed2001

Secondary failure of platelet recovery after hematopoietic stem cell transplantation.

After primary recovery of platelet counts after transplantation, there can be a late persistent decline called secondary failure of platelet recovery (SFPR), which may occur although the counts of other cell lineages remain within the normal range. SFPR was defined as a decline of platelet counts below 20,000/microL for 7 consecutive days or requiring transfusion support after achieving sustained platelet counts > or = 50,000/microL without transfusions for 7 consecutive days after hematopoietic stem cell transplantation (HSCT). The study population consisted of 2871 consecutive patients receiving transplants from January 1990 to March 1997. After primary recovery of platelet counts, SFPR not due to relapse of the underlying disease was observed in 285 of 1401 (20%) patients undergoing allogeneic transplantation and 36 (8%) of 444 patients undergoing autologous transplantation, with a median time of onset after transplantation at day 63 (range, day 21-156) and day 44 (range, day 24-89), respectively. Concomitant neutropenia was seen in 57 (20%) of 285 patients undergoing allogeneic HSCT and 7 (19%) of 36 patients undergoing autologous HSCT with SFPR. By multivariable analysis, the following were factors significantly associated with SFPR after allogeneic HSCT: a transplant from an unrelated donor; a graft-versus-host disease (GVHD) prophylaxis other than methotrexate and cyclosporine; development of grade 2 through 4 acute GVHD; impaired renal or liver function; conditioning with the combination of busulfan, cyclophosphamide, and total body irradiation; stem cell dose; and infections. Cytomegalovirus infection after engraftment and source of stem cells were the only significant risk factors after autologous HSCT. The hazard rate of death was significantly higher in patients who experienced SFPR (hazard ratio = 2.6 for allogeneic HSCT; hazard ratio = 2.2 for autologous HSCT). SFPR was associated with serious complications and poor outcome after transplantation. The identification of the characteristics and risk factors for SFPR could improve patient counseling and management and lead to the design of effective treatment strategies.

Adolescent↗