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Biomedical subjects

M L Barnes

Publications and source records attributed to M L Barnes.

18 recordsLinked to original sources
PubMed2007

Combined mediator blockade or topical steroid for treating the unified allergic airway.

BACKGROUND: Asthma and allergic rhinitis are manifestations of a single unified allergic airway, for which the best treatment is uncertain. OBJECTIVE: To compare the anti-inflammatory efficacy in the unified allergic airway of combined oral mediator antagonism and combined topical steroid. METHODS: Subjects with asthma and perennial allergic rhinitis entered a randomized double blind crossover study comparing montelukast 10 mg and cetirizine 10 mg to extra-fine inhaled beclomethasone 400 mcg/day and intranasal beclomethasone 200 mcg/day, each taken once daily for 2 months, after 2-week placebo washouts. Measurements were made after each washout and randomized treatment, comprising: methacholine PC20, exhaled and nasal nitric oxide, blood eosinophils and eosinophilic cationic protein, symptoms, lung and nasal function tests. RESULTS: Seventeen patients completed per protocol. For PC20 and exhaled nitric oxide, only combined topical steroid produced improvements (P < 0.005) from placebo baseline. Combined steroid was superior by a 0.93 (95% CI 0.14-0.93, P < 0.05) doubling dilution difference for PC20 and a 0.99 (95% CI 0.9-15.1, P < 0.01) doubling difference for exhaled nitric oxide. Both treatments attenuated eosinophils and eosinophilic cationic protein, and reduced nasal symptoms (P < 0.05). Only steroid improved nasal nitric oxide (P=0.05) and asthma symptoms (P < 0.05). Neither treatment affected lung or nasal function tests. CONCLUSION: Combined topical steroid and combined mediator antagonism both attenuated systemic inflammation in the unified allergic airway, but only the former reduced bronchial and nasal inflammatory markers. The relevance of this to exacerbations and airway remodelling needs to be defined.

Acetates↗
PubMed2006

Evaluation of quality of life and psychiatric morbidity in patients with malignant tumours of the skull base.

In general, patients with malignant tumours of the skull base have a poor prognosis. Treatment may have a disfiguring physical and disabling mental effect on patients. To evaluate the effect of treatment on physical and mental quality of life in patients with skull base malignancy, we conducted a cross-sectional patient survey of 18 patients treated for such tumours, using the University of Washington (version 4) quality of life questionnaire and the hospital anxiety and depression scale. The total quality of life score (median value) was 980 (550-1125). Patients with anterior skull base malignancy scored lower than those with lateral skull base malignancy (p=0.003). In general, the worst individual domain scores were: mood (64 per cent); activity (69 per cent); and, specifically for patients with anterior skull base malignancy, taste (54 per cent, p=0.004) and anxiety (60 per cent, p=0.034). One-third of skull base cancer patients were at risk of suffering from mental distress and psychiatric morbidity (indicated as a score of more than seven on the hospital anxiety and depression scale).

Adult↗
PubMed2006

Effects of levocetirizine as add-on therapy to fluticasone in seasonal allergic rhinitis.

BACKGROUND: Addition of H(1) antagonists to intranasal corticosteroid treatment of allergic rhinitis (AR) is common in clinical practice and recommended by guidelines, despite some evidence that the additive benefits are negligible. OBJECTIVE: To assess additional benefits of 5 mg levocetirizine dihydrochloride in seasonal AR patients using 200 mcg fluticasone propionate nasal spray once daily. METHODS: In a double-blind placebo-controlled crossover study of 27 patients, following 2 weeks without treatment, subjects used fluticasone with levocetirizine or identical placebo for 2 weeks each. Assessments were the Juniper mini Rhinoconjunctivitis Quality-of-Life Questionnaire (mini-RQLQ), domiciliary peak nasal inspiratory flow (PNIF), total nasal symptoms (TNS) scores and nasal nitric oxide concentrations. Effects were interpreted and tested against minimal clinically important differences. RESULTS: Add-on effects for levocetirizine vs. placebo excluded any clinically significant benefits: mean effects (one sided 95% confidence intervals) were mini-RQLQ -0.11 (-0.34), PNIF +0.57 (+5.23), and TNS -0.11 (-0.60). Numbers needed to treat (95% confidence intervals) by outcome were mini-RQLQ 14 (5 to 49), PNIF 4 (3-7), and TNS 3 (2-6). No significant within or between treatment effects were seen for nasal nitric oxide. CONCLUSION: Contrary to current practice, the present results demonstrate that for the majority of patients, antihistamine add-on to effective nasal steroid treatment is inappropriate. Further work is required to confirm that this is also true in the most severe cases, and the available evidence needs to be put into guidelines and implemented.

Administration, Intranasal↗
PubMed2006

Effects of intranasal corticosteroid on nasal adenosine monophosphate challenge in persistent allergic rhinitis.

BACKGROUND: Response to a single dose nasal adenosine monophosphate challenge has been used as a surrogate inflammatory marker for allergic rhinitis. Attenuation of response following intranasal corticosteroid would further validate the challenge. OBJECTIVE: To assess the effect of 4 weeks of 200 mcg once daily mometasone furoate nasal spray on a simplified (single 160 mg dose) nasal adenosine monophosphate challenge. METHODS: Twenty participants with persistent allergic rhinitis completed a double blind placebo-controlled crossover study. Outcome measures were the peak nasal inspiratory flow and total nasal symptoms score responses to nasal adenosine monophosphate challenge, as well as domiciliary peak nasal inspiratory flow and patient symptom diary cards. RESULTS: Mometasone significantly (P < 0.05) attenuated response time profiles vs. placebo for peak nasal inspiratory flow but not total nasal symptom scores. For the maximum percentage fall this amounted to a mean difference of 9.6% (95% confidence interval 1.3-17.9%). The coefficient of variation for repeatability was 48.7%. Improvements were seen in prechallenge and domiciliary measurements of peak nasal inspiratory flow (both P < 0.05) and total nasal symptom scores (both P < 0.01). CONCLUSIONS: Mometasone attenuates the peak nasal inspiratory flow response to a single 160 mg nasal adenosine monophosphate challenge. Such challenges have been shown to be sensitive to the effects of antihistamines, antileukotrienes and now nasal steroids. This further supports their application as surrogate inflammatory markers for therapeutic trials in allergic rhinitis, potentially as 20 min challenges which can be conducted in a non-hospital setting.

Adenosine Monophosphate↗
PubMed1999

Alpha-galactose based neoglycopeptides. Inhibition of verotoxin binding to globotriosylceramide.

Solution and solid phase strategies for the synthesis of alpha-galactose based neoglycopeptide derivatives 2-13 were developed. Neoglycopeptides generated were tested for the inhibition of verotoxin binding to globotriosylceramide (Gb3) using ELISA. Among all of the compounds tested, only the lipid derivatives of neoglycopeptides, 11, 12 and 13 were found to be inhibitors, IC50 = 2.0 mM (11b and 12c) and 0.2 mM (11c and 13c). All of the inhibitors (11b, 11c, 12c and 13c) have a similar branching of the two alpha-galactosyl units at the N-terminal glycine residue of a short peptide and a lipid moiety attached at the C-terminal site. Both of these factors seem to be crucial for the inhibition. It is interesting to note that the inhibitors have only a portion of the natural trisaccharide ligand. The secondary groups either may contribute in sub-site oriented interactions with the protein receptors or may mimic the internal sugar units of the cell-surface ligand, Gb3.

Anti-Infective Agents↗
PubMed1998

Diversity of C-linked neoglycopeptides for the exploration of subsite-assisted carbohydrate binding interactions.

Diversity of alpha-galactose based C-linked neoglycopeptides (1b, 2b, 3c, 4d, and 5d) has been developed to explore the importance of subsite-assisted carbohydrate binding interactions. Deprotected C-linked neoglycopeptides (1b, 2b, 3c, 4d, and 5d) were synthesized and tested in competitive inhibition assays using a model enzyme-linked lectin (e.g., Maclura pomifera). Compound 2b, with two alpha-galactoside units on the side chain of the lysine residue of the dipeptide backbone, exhibited a remarkable effect with a 2.82-fold increase in its inhibitory properties (IC50 1.48 mM) in comparison to 1b (IC50 4.18 mM).

Binding Sites↗
PubMed1987

Comparison of cancer chemotherapeutic agents in asynchronous and synchronous 9L cells.

The cytotoxic activity of various chemotherapy agents was investigated in asynchronous populations of cultured 9L rat brain tumor cells, and as a function of their position in the cell cycle. Representative drugs from the classes of DNA-active agents, alkylating agents, spindle poisons, and antimetabolites were tested. The ability to induce cell lethality in asynchronous populations as a function of drug concentration varied for 1 hr pulse exposures. In order of decreasing cytotoxic activity, DHAQ was the most effective, followed by VCR, VDS, VBL, ADR, BCNU, cis-DDP, BLM, DBD, RZ, and HU. The effect of chemotherapy agents on synchronous 9L cells obtained by mitotic selection also varied with respect to the individual agent and was cell cycle-dependent. Survival age-responses ranged from being minimal to demonstrating significant fluctuations as a function of cell cycle position. For all agents except ADR and HU, the sensitivity of G1 phase was greater than S phase. RZ exhibited essentially a flat age-response. Comparison of the cell cycle age-responses of chemotherapeutic agents to those exhibited by the cytotoxic modalities of radiation and hyperthermia demonstrate several unique differences.

Animals↗
PubMed1983

Correlation of the structure of amino-substituted anthraquinones to cytotoxicity in cultured Chinese hamster cells.

A number of substituted anthraquinones (SAQs) are currently being tested as cancer chemotherapeutic agents because of their structural similarity to Adriamycin (ADR) and other DNA-intercalating antibiotics. In this study, the effect of SAQs on the induction of cytotoxicity of asynchronous Chinese hamster cells in culture was studied and compared to those produced by ADR and dihydroxyanthraquinone (DHAQ), a SAQ previously shown to be more effective than ADR. SAQs produced cytotoxicity that was dependent upon the concentration and duration of drug exposure. A correlation was noted between the activity of a compound (the concentration required to produce a certain level of cell kill) and the presence of a particular triangular arrangement of one nitrogen atom and two oxygen atoms. There was also a correlation between chemical structure and antitumor activity in the murine P388 leukemia model system. This correlation between chemical structure and biological activity may aid in the development of new SAQs with greater potential as cancer chemotherapeutic agents.

Animals↗