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D Brooks

Publications and source records attributed to D Brooks.

At least 37 records · Page 2Linked to original sources

A qualitative systematic overview of the measurement properties of functional walk tests used in the cardiorespiratory domain.

OBJECTIVE: To perform a qualitative systematic overview of the measurement properties of the most commonly utilized walk tests in the cardiorespiratory domain: the 2-min walk test (2MWT), 6-min walk test (6MWT), 12-min walk test (12MWT), self-paced walk test (SPWT), and shuttle walk test (SWT). DATA SOURCES: MEDLINE (1966 to January 2000) and CINAHL (1982 to December 1999) electronic databases were searched. Bibliographies of the retrieved articles were reviewed. STUDY SELECTION: Clinical trials and observational studies were included if they reported data on the validity, reliability, interpretability, or responsiveness of the 2MWT, 6MWT, 12MWT, SPWT, or SWT. Only studies conducted on patients with cardiac and/or respiratory involvement were included. RESULTS: Fifty-two studies examining measurement properties of the various walk tests were found: 5 studies on the 2MWT, 29 studies on the 6MWT, 13 studies on the 12MWT, 6 studies on the SPWT, and 4 studies on the SWT. Measurement properties were most strongly demonstrated for the 6MWT. Correlations of 6MWT distance and maximal oxygen consumption ranged from 0.51 to 0.90. A change in distance walked of at least 54 m was found to be clinically significant for the 6MWT. Reliability was shown to be optimized when the administration of walk tests was standardized and at least two practice walks were performed. Patients with increased likelihood of postoperative complications, hospitalization, and death were identified by analysis of distance walked. CONCLUSIONS: Measurement properties of the 6MWT have been the most extensively researched and established. In addition, the 6MWT is easy to administer, better tolerated, and more reflective of activities of daily living than the other walk tests. Therefore, the 6MWT is currently the test of choice when using a functional walk test for clinical or research purposes.

Adult↗

Nutritional intervention in COPD: a systematic overview.

OBJECTIVE: We conducted a systematic overview of randomized controlled trials (RCTs) to clarify the contribution of nutritional supplementation for patients with stable COPD. METHODS: RCTs were identified from several sources, including the Cochrane Airways Group register of RCTs, a hand search of abstracts presented at international meetings, and consultation with experts. Two reviewers independently selected trials for inclusion, assessed quality, and extracted the data. RESULTS: Twenty-one reports were classified according to the type, duration of supplementation, and the presence of anabolic substances. High carbohydrate meals were associated with an increase in carbon dioxide production and a decrease in exercise capacity. Short-term crossover studies in which diets of various compositions were administered supported the notion that high carbohydrate loads increase the stress on the ventilatory system. The influence of longer-term supplementation (> 2 weeks) on weight, anthropometry, and exercise capacity varied, without there being a consistent effect. Lean body weight was only occasionally reported and health-related quality of life too rarely to be included as an outcome. The influence of recombinant human growth hormone was disappointing. Anabolic steroids increased body weight and lean body mass, but had little influence on exercise capacity. CONCLUSION: This systematic overview in patients with COPD supports the notion that those with marginal ventilatory reserve might benefit from a dietary regimen in which a high percentage of calories are supplied by fat. Although there are reports of the benefits of nutritional repletion, trials of > 2 weeks failed to show consistent benefit on body weight. Evaluating nutritional repletion is hampered by the absence of information regarding body composition, exercise, and health-related quality of life. Growth hormone has not been shown to be useful. Further studies are needed to refine the beneficial effects of anabolic steroids as adjunctive agents together with nutritional support and exercise.

Anabolic Agents↗

Effect of food on the oral bioavailability of UFT and leucovorin in cancer patients.

UFT is composed of tegafur (FT), a prodrug of 5-fluorouracil (5-FU), and uracil in a fixed combination (1:4). In conjunction with leucovorin, UFT is being developed for the first-line oral treatment of metastatic colorectal cancer. The effect of food on the oral bioavailability of UFT (2 x 100 mg capsules; dose in terms of FT) and leucovorin (2 x 15 mg tablets) was evaluated in a single-dose, randomized, two-way crossover study. Patients (n = 25) were assigned to receive both drugs after an overnight fast or 5 min after completion of a high-fat meal (721 calories) with a 3-day washout period between treatments; then they were permitted to continue on oral UFT/leucovorin therapy for safety assessment. UFT (300 mg/m2/day as three divided doses) and leucovorin (90 mg/day as three divided doses) were given for 28 days. After a 7-day rest, the 28-day cycle was repeated. Pharmacokinetics (n = 22 patients) were determined for FT, 5-FU, uracil, leucovorin, and 5-methyltetrahydrofolate (an active metabolite of leucovorin). The absence of food-effect on peak plasma concentration (CMAX) and the area under the curve (AUC) was concluded if the 90% confidence interval for the ratio of the treatment means was entirely contained in 0.75-1.33. Administration of UFT with food resulted in a 34% decrease in CMAX of FT, whereas the AUC of FT remained unchanged. Food decreased the CMAX and AUC values of uracil and 5-FU by 37-76%. On the contrary, the CMAX and AUC values of leucovorin and 5-methyltetrahydrofolate were increased by 14-60% with food. Time to reach CMAX for all analytes was significantly (P < or = 0.001) delayed by food. Except for the AUCs of FT, the statistical criterion for concluding a lack of food-effect was not met. These data suggest that UFT/leucovorin should not be dosed simultaneously with food. It is recommended that food should not be consumed for 1 h before and after an oral dose of UFT and leucovorin in a manner similar to pivotal Phase III trials. The 28-day oral regimen of UFT and leucovorin was generally well tolerated in the population studied.

Administration, Oral↗

Nutritional supplementation in stable chronic obstructive pulmonary disease.

BACKGROUND: Low body weight in patients with chronic obstructive pulmonary disease (COPD) is associated with an impaired pulmonary status, reduced diaphragmatic mass, lower exercise capacity and higher mortality rate when compared to adequately nourished individuals with this disease. Nutritional support may therefore be a useful part of their comprehensive care. OBJECTIVES: To conduct a systematic review of randomized controlled trials (RCTs) to clarify whether nutritional supplementation (caloric supplementation for at least 2 weeks) improved anthropometric measures, pulmonary function, respiratory muscle strength and functional exercise capacity in patients with stable COPD. SEARCH STRATEGY: Randomized controlled trials (RCTs) were identified from the Cochrane Airways Group register of RCTs, a hand-search of abstracts presented at international meetings and consultation with experts. SELECTION CRITERIA: Two reviewers independently selected trials for inclusion, assessed quality and extracted the data. DATA COLLECTION AND ANALYSIS: Within each trial and for each outcome, we calculated an effect size. The effect sizes were then pooled by a random-effects model. Homogeneity among the effect sizes was also tested. MAIN RESULTS: From 272 references, nine RCTs were ultimately included. Six papers were considered as high quality and only two studies were double-blinded. For each of the outcomes studied, the effect of nutritional support was small: the 95% confidence intervals around the pooled effect sizes all included zero. The effect of nutritional support was homogeneous across studies. REVIEWER'S CONCLUSIONS: Nutritional support had no significant effect on anthropometric measures, lung function or exercise capacity in patients with stable COPD.

Enteral Nutrition↗

CD8+, CD57+ T cells from healthy elderly subjects suppress neutrophil development in vitro: implications for the neutropenia of Felty's and large granular lymphocyte syndromes.

OBJECTIVE: To investigate the ability of CD8+,CD57+ large granular lymphocytes (LGL) from normal individuals and from Felty's syndrome (FS) or LGL syndrome patients to suppress allogeneic neutrophil precursor development. METHODS: Six FS patients, 5 LGL syndrome patients, and 13 elderly controls were studied. CD8+,CD57+ T cells were cocultured with cord blood-derived stem cells, and percentage inhibition was calculated. Recombinant chemokines and Fas-stimulating molecules were used in separate cultures to address possible mechanisms of suppression. Proliferation after stimulation with interleukin-2 (IL-2) and anti-CD3 was assessed. RESULTS: Significant (79%) suppression of colony-forming unit-granulocyte-macrophage (CFU-GM) by the CD8+,CD57+ subset was shown by 1 FS patient. None of the CD8+,CD57+ cells from LGL syndrome patients had any effect. Six of 13 controls studied showed >40% inhibition of CFU-GM, and all but 2 showed at least some suppression. The suppressive effect was not mediated by Fas/Fas ligand interactions or by the chemokines macrophage inhibitory protein 1alpha or IL-8. LGL from both patients and controls were largely CD28- and had reduced proliferative capacity. CONCLUSION: In a subset of FS patients, expansion of CD8+,CD57+ T cells in the bone marrow may be responsible for neutropenia by suppressing neutrophil precursors. This effect is also seen with normal LGL, which are likely to have an important function in neutrophil homeostasis.

Aged↗

Transgenic plants as factories for biopharmaceuticals.

Plants have considerable potential for the production of biopharmaceutical proteins and peptides because they are easily transformed and provide a cheap source of protein. Several biotechnology companies are now actively developing, field testing, and patenting plant expression systems, while clinical trials are proceeding on the first biopharmaceuticals derived from them. One transgenic plant-derived biopharmaceutical, hirudin, is now being commercially produced in Canada for the first time. Product purification is potentially an expensive process, and various methods are currently being developed to overcome this problem, including oleosin-fusion technology, which allows extraction with oil bodies. In some cases, delivery of a biopharmaceutical product by direct ingestion of the modified plant potentially removes the need for purification. Such biopharmaceuticals and edible vaccines can be stored and distributed as seeds, tubers, or fruits, making immunization programs in developing countries cheaper and potentially easier to administer. Some of the most expensive biopharmaceuticals of restricted availability, such as glucocerebrosidase, could become much cheaper and more plentiful through production in transgenic plants.

Antibodies↗

Major histocompatility complex haplotypic associations in Felty's syndrome and large granular lymphocyte syndrome are secondary to allelic association with HLA-DRB1 *0401.

OBJECTIVE: To investigate the role of HLA class I in susceptibility to Felty's syndrome (FS) and large granular lymphocyte (LGL) syndrome. METHODS: Fifty caucasoid FS patients, and 55 patients with LGL syndrome, of whom 26 had arthritis and 29 did not, were studied. Complete HLA class I and HLA-DR typing including, where relevant, DRB1*04 subtyping was carried out by molecular methods. Comparison was made with 78 unselected healthy caucasoid controls and a further 29 DRB1*0401+ individuals. RESULTS: A significant association was found between HLA-A*02 and FS [odds ratio (OR) 3.9, 95% confidence interval (95% CI) 1.8-8.4, P = 0.0004]. At the B locus, there was an association between B*44 and LGL with arthritis [OR 3.5 (1.3-9.2), P = 0.01]. For HLA-Cw*0501, there was an association with FS [OR 4 (1. 7-9.2) P = 0.0008]. For both FS and LGL with arthritis, the extended haplotype HLA-A*02;B*44;Cw*0501;DRB1*0401 was significantly associated [OR 9.5 (2.6-35), P = 0.0001; OR 4.6 (1-22.4), P = 0.05, respectively]. There was no association between HLA class I or II and LGL without arthritis. All the allelic and haplotypic associations were lost on comparison with HLA-DRB1*0401+ controls. The strongest HLA association was with HLA-DRB1*0401 for FS [OR 27.9 (10.3-75.5), P = 10(-13)], and LGL with arthritis [OR 35.4 (9.6-131. 3), P = 10(-10)]. CONCLUSIONS: The major histocompatibility locus (MHC) associations with FS reported here are due to linkage disequilibrium with HLA-DRB1*0401. LGL syndrome with arthritis shows identical class II associations with FS, although there may be subtle immunogenetic differences between the two in the class I region. One of the extended haplotypes reported in a number of studies for FS and rheumatoid arthritis (summarized as HLA-A*02;Cw*0501; B*44;TNFb5;TNFa6;TNFd4;C4A*3;C4BQ*0;DRB1*0 401;DQB1*0301) is likely to be attributable to strong primary association with HLA-DRB1*0401, rather than to epistatic interaction between these loci.

Adult↗

Identification of a novel kidney-specific gene downregulated in acute ischemic renal failure.

To gain further insights into the molecular mechanisms involved in acute renal failure, we have isolated a new gene from rat and human, named KSP32 (kidney-specific protein with a molecular mass of 32 kDa). KSP32 encodes a novel gene that shows little homology to other mammalian proteins. It, however, shares extensive homology with several proteins found in the nematode Caenorhabditis elegans and plants. The expression of KSP32 mRNA is highly restricted to kidney. In situ hybidization analysis revealed that the expression of KSP32 mRNA was prominent in the boundary of kidney cortex and outer medulla, exhibiting a raylike formation extending from the medulla into the cortex. Finally, KSP32 mRNA was dramatically downregulated in rat following induction of acute ischemic renal failure. Rapid loss of KSP32 mRNA expression was observed beginning at approximately 5 h following renal injury and mRNA levels remained depressed for at least 96 h. Both KSP32 mRNA levels as well as renal function recovered 14 days after injury. Administration of an endothelin receptor antagonist (SB-209670), known to restore renal function, significantly increased KSP32 expression.

Acute Kidney Injury↗

Nutritional support for individuals with COPD: a meta-analysis.

RATIONALE: Malnutrition in patients with COPD is associated with an impaired pulmonary status, reduced diaphragmatic mass, lower exercise capacity, and higher mortality rate when compared to adequately nourished individuals with COPD. Nutritional support may therefore be a useful part of their comprehensive care. PURPOSE: To conduct a meta-analysis of randomized controlled trials (RCTs) to clarify whether nutritional supplementation (caloric supplementation for at least 2 weeks) improved anthropometric measures, pulmonary function, respiratory muscle strength, and functional exercise capacity in patients with stable COPD. METHODS: RCTs were identified from several sources, including the Cochrane Airways Group register of RCTs, a hand search of abstracts presented at international meetings, and consultation with experts. Two reviewers independently selected trials for inclusion, assessed quality, and extracted the data. Within each trial and for each outcome, we calculated an effect size. The effect sizes were then pooled by a random-effects model. Homogeneity among the effect sizes was also tested. RESULTS: From 272 references, nine RCTs were ultimately included. Six articles were considered as high quality. Only two studies were double blinded. For each of the outcomes studied, the effect of nutritional support was small: the 95% confidence intervals around the pooled effect sizes all included zero. The effect of nutritional support was homogeneous across studies. CONCLUSION: Nutritional support had no effect on improving anthropometric measures, lung function, or functional exercise capacity among patients with stable COPD.

Combined Modality Therapy↗

Chemically modified oligonucleotides exhibit decreased immune stimulation in mice.

Phosphorothioate oligodeoxynucleotides produce splenomegaly and mononuclear cell infiltrates in multiple organs in mice after repeated i.v. administration. Several phosphorothioate oligodeoxynucleotides were studied to better understand the basis of immunostimulatory properties of these molecules in mice and to study the effects of chemically modified oligonucleotides. Chemical modifications examined included 5-methyl cytosine and 2'-methoxyethoxy substituents. Male mice (six per group) were treated with oligonucleotide concentrations of 0, 2, 10, or 50 mg/kg by i.v. injection every other day for 14 days. Immune stimulation was assessed 24 h after the last dose by measuring spleen weight, or histologic and immunohistochemical examination of liver and kidney. Immune stimulation was dose-dependent for the phosphorothioate oligodeoxynucleotides studied, but potency varied as a function of sequence. Results from this study reveal that there is a close correlation between the extent of splenomegaly and other evidence of immune stimulation, such as the severity of cell infiltrates in liver and kidney in mice. Immunohistochemical analysis indicated that cell infiltrates in liver and kidney were primarily mononuclear cells associated with increased expression of the endothelial-leukocyte cellular adhesion molecule intracellular adhesion molecule-1 and the cytokine interleukin-6. Immune stimulation was markedly decreased with oligonucleotides containing the 5-methyl cytosine and further decreased by 2'-methoxyethoxy modifications. Administration of these modified oligonucleotides to mice did not produce splenomegaly even at the 50-mg/kg dose, and only produced minimal cell infiltrates despite the presence of comparable or greater tissue oligonucleotide concentrations. Thus, chemical modifications appeared to increase the tolerability profile for these compounds that are representative of the second generation of antisense oligonucleotides.

Alanine Transaminase↗

Public knowledge, awareness, and perceptions of the association between skin aging and smoking.

BACKGROUND: Although the tobacco industry promotes images of glamour, 2 decades of epidemiologic research have concluded the opposite: smokers have enhanced facial aging and skin wrinkling compared with nonsmokers. OBJECTIVE: The purpose of this study was to obtain information on the public's awareness of the association between cigarette smoking and skin aging. METHODS: In the spring of 1994, the Maine-wide Cooperative Telephone Survey conducted telephone interviews in 678 randomly selected, nonseasonal dwelling units in Maine. From each dwelling unit, one randomly selected adult resident was interviewed to assess awareness of the association of skin aging with smoking. RESULTS: Fifty-eight percent of those persons interviewed had smoked at least 100 cigarettes, and among them, 24% were current smokers (28% men, 21% women). After adjusting for sex, age, and education, current smokers remained less likely to be aware of this association compared with former (prevalence ratio, 0.78; 95% confidence interval, 0.64-0.95) and never smokers (prevalence ratio, 0.87; 95% confidence interval, 0.70-1.07). However, nearly one fourth of smokers in this study believed that most or some smokers would consider this information in their decision to quit, with slightly higher findings in young smokers. CONCLUSION: These findings are of public health importance. While strategies for framing messages about the association between smoking and facial aging await further study, this association deserves to be considered in all tobacco control and counter-advertising campaigns.

Adolescent↗

Adult transracial and inracial adoptees: effects of race, gender, adoptive family structure, and placement history on adjustment outcomes.

Adjustment outcomes of 224 transracial and inracial adoptees were investigated using data collected over 17 years. Findings reveal an association between adoptees' outcomes and their race, gender, and adoptive family structure. Placement history was not significant. Implications for policy and practice are discussed, as are future directions for research.

Adoption↗

Pergolide mesylate for cocaine abuse: a controlled preliminary trial.

A small, controlled study was conducted to assess whether pergolide mesylate has clinical promise as a treatment for cocaine abuse prior to embarking on a larger, randomized, double-blind, controlled trial. Fourteen individuals were placed on placebo for 2 weeks, followed by a 24-week single-blind study in which they were placed on pergolide for 12 weeks, followed by placebo for 12 weeks. Another 14 patients received single-blind placebo for two weeks and then were randomized into a 24-week double-blind, placebo-controlled, multiple baseline design. Initially, patients enrolled in the study were placed on risperidone (n = 9) or placebo (n = 5). During the first 12 weeks, retention was worse for those receiving pergolide compared to risperidone or placebo. Neither risperidone nor pergolide were more efficacious in reducing cocaine use than placebo. Although earlier open studies found pergolide to show promise as a treatment for cocaine abuse, this study did not support these earlier findings. Comparing an agent to both an active control and placebo group may better predict whether a promising new agent will have clinical utility compared to the standard open trial.

Adult↗

Adoption and race: implementing the Multiethnic Placement Act and the Interethnic Adoption Provisions.

Passage of the Multiethnic Placement Act of 1994 (MEPA) and the 1996 provisions on Removal of Barriers to Interethnic Adoption (Interethnic Adoption Provisions) provides an ideal opportunity to examine what can be done to increase adoptions of foster children, particularly children of color. To assist states and child welfare professionals in serving children better and meeting legal obligations, this article discusses racial matching, MEPA, and the Interethnic Adoption Provisions. Implications for practice and challenges in implementing the law also are discussed. The article suggests principles for adoption practice, recruitment, and placement that provide a framework for simultaneously meeting the requirements of the law and serving the best interests of children. Recommendations for practice, policy, and research are offered.

Adoption↗

Baroreflex control of heart rate in a canine model of obstructive sleep apnea.

We have recently demonstrated the development of systemic hypertension in a canine model of obstructive sleep apnea (OSA), but the underlying physiological mechanisms were not identified. Therefore, the purpose of this study was to examine the effect of OSA on arterial baroreceptor control of heart rate (HR) in this canine model. OSA was produced in three dogs for 1 to 3 mo. Baroreflex control of HR was determined with graded infusions of vasoactive agents (phenylephrine and nitroprusside) administered over 30 to 60 s, during which steady-state systolic blood pressure (BP) and cardiac R-R interval responses were recorded. BP was measured with a permanently implanted arterial catheter and a telemetry system. Although, as previously reported, OSA resulted in increases in daytime (awake) mean BP of 6.0 to 26.8 mm Hg, there was no change in daytime baseline HR or in the slope of the systolic BP-R-R interval curve (p > 0.2). The findings demonstrate that OSA in the dog is associated with resetting of the baroreceptors to a higher pressure, but no change in baroreflex sensitivity.

Animals↗