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Biomedical subjects

V Lund

Publications and source records attributed to V Lund.

At least 19 recordsLinked to original sources

Pharmacologic and anti-IgE treatment of allergic rhinitis ARIA update (in collaboration with GA2LEN).

The pharmacologic treatment of allergic rhinitis proposed by ARIA is an evidence-based and step-wise approach based on the classification of the symptoms. The ARIA workshop, held in December 1999, published a report in 2001 and new information has subsequently been published. The initial ARIA document lacked some important information on several issues. This document updates the ARIA sections on the pharmacologic and anti-IgE treatments of allergic rhinitis. Literature published between January 2000 and December 2004 has been included. Only a few studies assessing nasal and non-nasal symptoms are presented as these will be discussed in a separate document.

Animals↗

The national comparative audit of surgery for nasal polyposis and chronic rhinosinusitis.

OBJECTIVES: This study summarises the results of a National Audit of sino-nasal surgery carried out in England and Wales. It describes patient and operative characteristics as well as patient outcomes up to 36 months after surgery. DESIGN: Prospective cohort study. SETTING: NHS hospitals in England and Wales. PARTICIPANTS: Consecutive patients undergoing surgery for nasal polyposis and/or chronic rhinosinusitis. MAIN OUTCOME MEASURE: The total score derived from a 22-item version of the Sino-Nasal Outcome Test (SNOT-22). Lower scores represent better health-related quality of life. RESULTS: A total of 3128 consecutive patients at 87 NHS hospitals were enrolled. There is a large improvement in SNOT-22 scores from the pre-operative period (mean = 42.0) to 3 months after surgery (mean = 25.5). The scores for patients undergoing nasal polypectomy improved from 41.0 before surgery to 23.1 at 3 months after surgery, while the scores for patients undergoing surgery for chronic rhinosinusitis alone improved from 44.2 to 31.2. The SNOT-22 scores reported at 12 and 36 months after surgery were similar to those reported at 3 months. Excessive bleeding occurred in 5% of patients during the operation and in 1% of patients after the operation. Intra-orbital complications were reported in 0.2%. Of those patients undergoing primary surgery for bilateral grade I or II polyposis, 18% had not received a pre-operative course of steroid treatment. At the 36-month follow-up, 11.4% of patients had undergone revision surgery. CONCLUSIONS: The audit confirms that sino-nasal surgery is generally safe and effective. There is some evidence that patient selection for surgery could be improved.

Adolescent↗

Biofilm in water pipelines; a potential source for off-flavours in the drinking water.

Volatile organic compounds (VOC) are identified in natural biofilm established in plastic pipes used at the drinking water supply. Odour potent VOCs such as ectocarpene, dictyopterene A and C', geosmin, beta-ionone, 6-methyl-5-hepten-2-one, menthol and menthone were prominent compounds in biofilm in the distribution network and at raw water test sites, and are associated with algae and cyanobacteria present in the raw water source.

Biofilms↗

Instantaneous beat-to-beat variability reflects vagal tone during hyperbaric hyperoxia.

Hyperbaric hyperoxia affects heart rate variability (HRV) by increasing parasympathetic activity. The purpose of this study was to evaluate the applicability of instantaneous beat-to-beat variability (SD1 of Poincaré plot analysis) in detecting changes in vagal tone and to evaluate possible changes in the fractality of heart rate dynamics (alpha1 of detrended fluctuation analysis) during hyperbaric hyperoxia. Continuous three-lead ECG recordings were taken in ten divers who were treated at 2.5 ATA with air (PO2 47 kPa) and oxygen (PO2 235 kPa) for 60 min. Power spectral analysis, Poincaré plot analysis and alpha1 were analyzed before compression, after 30 min and after 55 min at 2.5 ATA. Correlations between the variables were calculated after 55 min exposure. SD1 and high frequency (HF) power increased significantly but alpha1 decreased during hyperbaric hyperoxia (PO2 235 kPa). HF power and SD1 also correlated significantly. However, HF power and SD1 correlated inversely with alpha1. During hyperbaric hyperoxia, SD1 reflects vagal activity and can be used instead of HF power, if stationary conditions cannot be achieved. The decreasing alpha1 indicates more random heart rate dynamics during hyperbaric hyperoxia.

Diving↗

The toxicity of styrene to the nasal epithelium of mice and rats: studies on the mode of action and relevance to humans.

Inhaled styrene is known to be toxic to the nasal olfactory epithelium of both mice and rats, although mice are markedly more sensitive. In this study, the nasal tissues of mice exposed to 40 and 160 ppm styrene 6 h/day for 3 days had a number of degenerative changes including atrophy of the olfactory mucosa and loss of normal cellular organisation. Pretreatment of mice with 5-phenyl-1-pentyne, an inhibitor of both CYP2F2 and CYP2E1 completely prevented the development of a nasal lesion on exposure to styrene establishing that a metabolite of styrene, probably styrene oxide, is responsible for the observed nasal toxicity. Comparisons of the cytochrome P-450 mediated metabolism of styrene to its oxide, and subsequent metabolism of the oxide by epoxide hydrolases and glutathione S-transferases in nasal tissues in vitro, have provided an explanation for the increased sensitivity of the mouse to styrene. Whereas cytochrome P-450 metabolism of styrene is similar in rats and mice, the rat is able to metabolise styrene oxide at higher rates than the mouse thus rapidly detoxifying this electrophilic metabolite. Metabolism of styrene to its oxide could not be detected in human nasal tissues in vitro, but the same tissues did have epoxide hydrolase and glutathione S-transferase activities, and were able to metabolise styrene oxide efficiently, indicating that styrene is unlikely to be toxic to the human nasal epithelium.

Alkynes↗

Methyl methacrylate toxicity in rat nasal epithelium: studies of the mechanism of action and comparisons between species.

Female F344 rats exposed to 200 ppm methyl methacrylate for 6 h developed a lesion in the nasal olfactory epithelium which was characterised by degeneration and atrophy. The severity of the lesion was markedly reduced by pre-treatment of the rats with an intraperitoneal dose of 100 mg/kg bis-(p-nitrophenyl)phosphate, an inhibitor of carboxylesterase enzymes, thus demonstrating that the lesion is caused by the carboxylesterase mediated metabolism of methyl methacrylate to methacrylic acid, an irritant and corrosive metabolite. The distribution of the carboxylesterases in nasal tissues has been investigated and the metabolism of methyl methacrylate to methacrylic acid has been compared in rat, hamster and human nasal tissue fractions in vitro. Histocytochemistry showed that the carboxylesterases are heavily localised in the sustentacular cells and Bowman's glands of the rat olfactory region, but are more generally distributed in human olfactory epithelium. Consistent with this, the enzyme activity in all three species was higher in fractions prepared from olfactory tissue than from respiratory tissue, 3-fold in rat and human and 12-fold in the hamster. The maximum rates (V(max)) of metabolism in rat and hamster olfactory tissue fractions were comparable, whereas those in human olfactory tissue fractions were at least 13-fold lower. The rate of metabolism in rat olfactory tissue was also comparable to that in rat liver whereas in humans, the rate in olfactory tissue was 500-fold lower than that in the liver. In respiratory tissues, the rate in humans was at least 6-fold lower than that in the rat. These results suggest that humans are significantly less sensitive than rodents to the nasal toxicity of methyl methacrylate.

Animals↗

Recurrence and its avoidance in juvenile angiofibroma.

OBJECTIVE: Angiofibroma is a highly vascular lesion for which a wide range of surgical approaches has been recommended. Irrespective of the approach, a significant and often rapid recurrence rate is reported in all major series. AIM: To consider the impact of lessons learned from imaging on the recurrence rate of angiofibroma. MATERIAL AND METHODS: From a cohort of 90 male patients with histologically proven angiofibroma, 40 individuals were studied. The recurrence rate in 20 cases treated before March 1998 was compared with that in 19 cases treated thereafter. In the latter group, an additional exploration of the basisphenoid had been undertaken. RESULTS: The two cohorts were comparable in age range (7-27 y and 11-24 years, respectively), and all had been treated by midfacial degloving. In the first group, 8 recurrences occurred which were multiple in 1 patient. In the next 19 patients, the area of the pterygoid canal was meticulously explored and the basisphenoid drilled to remove all residual tumor. No recurrences have occurred in this group during a follow-up of between 6 months to 3 years. CONCLUSION: Meticulous removal of angiofibroma infiltrating the pterygoid canal and basisphenoid is paramount to avoid "recurrence."

Adolescent↗

Topical corticosteroids in nasal polyposis.

Nasal polyps are the common end-point of a number of conditions characterised by inflammation and are rarely 'curable' in its true sense. After consideration of the underlying aetiology and confirmation of the diagnosis, they are normally managed by a combination of medical and surgical interventions. Of these, topical corticosteroids have proved to be the medical treatment of choice. The objectives of the medical management are to eliminate or reduce the size of polyps, re-establish nasal airway and nasal breathing, improve or restore the sense of smell, and prevent recurrence of nasal polyps. The mechanism of action of corticosteroids may be by a multifactorial effect on various aspects of the inflammatory reaction, the effect being initiated by their binding to a specific cytoplasmic glucocorticoid receptor. At a cellular level, there is a reduction in the number of antigen-presenting cells, in the number and activation of T cells, in the number of mast cells, and in the number and activation of eosinophils. When polyps are large (grade 3) topical medication is difficult to instil in a very blocked nose and surgery or short term systemic corticosteroids may be required. Topical corticosteroids are of use in the primary treatment of nasal polyps when they are of a small or medium size (grades 1 and 2) and in the maintenance of any therapeutic improvement. The efficacy of topical corticosteroids such as betamethasone sodium phosphate nose drops, beclomethasone dipropionate, fluticasone propionate and budesonide nasal sprays in reducing polyp size and rhinitis symptoms has been demonstrated in several randomised, placebo-controlled trials. Beclomethasone dipropionate, flunisolide and budesonide sprays have also been shown to delay the recurrence of polyps after surgery. Placebo-controlled studies of agents that have shown a significant clinical effect in the management of nasal polyposis are reviewed.

Administration, Topical↗

Hyperbaric oxygen increases parasympathetic activity in professional divers.

The role of autonomic nervous system in hyperoxic bradycardia was evaluated by using the power-spectral analysis of heart-rate variability (HRV). Ten professional divers went through two hyperbaric hyperoxic experiments: (1) hyperbaric oxygen (HBO), 100% oxygen at 2.5 ATA, (2) hyperbaric air (HBAIR), O(2) 21% at 2.5 ATA. Four-minute traces of ECG were registered and subjected to power-spectral analysis. Cardiac conduction parameters were evaluated by a diagnostic 12-lead ECG and arrhythmias by a continuous 3-lead ECG. Statistical analysis was made using analysis of variance for repeated measurements. Heart rate decreased (P < 0. 001), but the response was similar during both treatments (P=0.14). Total power increased significantly more during HBO than HBAIR (P=0.003). High-frequency (HF) power (P < 0.001), Hayano's index (P=0.001) and normalized units of HF power (P=0.002) increased and LF/HF index (P < 0.001) decreased more during HBO than HBAIR. There were no changes in cardiac conduction or incidence of arrhythmias. In conclusion, 100% oxygen at 2.5 ATA caused marked increase in parasympathetic tone compared with 21% oxygen at 2.5 ATA.

Analysis of Variance↗

Primary chordoma of the ethmoid sinus.

Primary chordoma of the paranasal sinuses are extremely rare tumours, with only a small number of cases verified and published in the literature. It appears that only five of these cases involved the ethmoid sinuses either as a primary or by local invasion, and of these documented cases only one other has been found to solely involve the ethmoid sinus. We present a case of primary ethmoid sinus chordoma treated by wide local surgical excision and present a review of the literature with regard to prevalence and treatment rationale.

Adult↗

Cellular infiltration and cytokine mRNA expression in perennial allergic rhinitis.

BACKGROUND: Allergen challenge in allergic rhinitis patients leads to local eosinophilia and Th2-type cytokine expression. Natural exposure to grass pollen is additionally characterized by epithelial mast-cell infiltration. We hypothesized that perennial allergic rhinitis is also associated with T-cell and eosinophil infiltration of the nasal mucosa, local Th2-type cytokine expression, and increased numbers of nasal epithelial mast cells. METHODS: Nasal biopsies from perennial allergic rhinitis patients and controls were analysed by immunocytochemistry for different cell populations and in situ hybridization for cytokine mRNA-expressing cells. RESULTS: Perennial allergic rhinitis was associated with increased numbers of submucosal CD3+ T cells (P=0.05), EG2+ activated eosinophils (P=0.01), and CD68+ macrophages (P=0.01) compared to controls. Epithelial, but not submucosal, tryptase-positive mast cells were also elevated in rhinitics compared to controls (P=0.01). The numbers of cells expressing interleukin (IL)-5 were higher (P=0.01) and the numbers of cells expressing IL-2 were lower (P=0.04) in rhinitic patients than controls. There were no significant differences for either IL-4 or interferon-gamma between the groups. CONCLUSIONS: Perennial allergic rhinitis is characterized by mast-cell migration into the epithelium; submucosal infiltration by T cells, eosinophils, and macrophages; and an imbalance in local T-cell cytokine production in favour of enhanced IL-5 and reduced IL-2 expression.

Adult↗

Inflammatory cell populations and cytokine mRNA expression in the nasal mucosa in aspirin-sensitive rhinitis.

Aspirin-sensitive rhinitis is characterized by severe perennial nasal congestion and discharge. The study questioned whether this disease, like immunoglobulin E-mediated rhinitis, might be associated with local recruitment and activation of T-lymphocytes, mast cells and eosinophils with parallel increases in "T-helper2-type" cytokines. Nasal biopsies from 10 patients with aspirin-sensitive rhinitis and 12 healthy controls subjects were studied. Nasal mucosal sections were examined by immunohistochemistry in order to determine cell phenotypes and by in situ hybridization to detect cells expressing messenger ribonucleic acid (mRNA) for cytokines. In aspirin-sensitive rhinitis there were increases in total (CD3+) (p=0.05) and activated (CD25+) T-cells (p=0.007), total (major basic protein (MBP) positive) (p=0.004) and activated (monoclonal antibody which recognizes the cleaved form of eosinophil cationic protein (EG2) positive) eosinophils (p=0.003), tryptase+ mast cells (p=0.04) and CD68+ macrophages (p=0.002). Neutrophils and cells expressing human leukocyte antigen-DR were no different. Marked increases were observed in the numbers of interleukin (IL)-5 mRNA+ cells (p=0.004) in aspirin-sensitive patients, whereas lower numbers of IL-4 mRNA+ cells were observed, with a trend for a difference from controls (p=0.07). No differences were observed for either IL-2 or interferon-gamma. In conclusion, in aspirin-sensitive rhinitis there is intense inflammation of the nasal mucosa characterised by T-lymphocytes, eosinophils and mast cells. The predominance of macrophages and disproportionate increase in interleukin-5 compared to interleukin-4 messenger ribonucleic acid expression suggests that factors other than "allergic" mechanisms may be important in this disease.

Adult↗

Detection of low numbers of Salmonella in environmental water, sewage and food samples by a nested polymerase chain reaction assay.

A polymerase chain reaction (PCR) assay with two nested pairs of primers selected from conserved sequences within a 2.3 kb randomly cloned DNA fragment from the Salmonella typhimurium chromosome was developed. The nested PCR assay correctly identified 128 of a total of 129 Salmonella strains belonging to subspecies I, II, IIIb and IV. One strain of Salm. arizona (ssp. IIIa) tested negative. No PCR products were obtained from any of the 31 non-Salmonella strains examined. The sensitivity of the assay was 2 cfu, as determined by analysis of proteinase K-treated boiled lysates of Salm. typhimurium. The performance of the assay was evaluated for environmental water, sewage and food samples spiked with Salm. typhimurium. Water and sewage samples were filtered and filters were enriched overnight in a non-selective medium. Prior to PCR, the broth cultures were subjected to a rapid and simple preparation procedure consisting of centrifugation, proteinase K treatment and boiling. This assay enabled detection of 10 cfu 100 ml(-1) water with background levels of up to 8700 heterotrophic organisms ml(-1) and 10000 cfu of coliform organisms 100 ml(-1) water. Spiked food samples were analysed with and without overnight enrichment in a non-selective medium using the same assay as above. Nested PCR performed on enriched broths enabled detection of <10 cfu g(-1) food. Variable results were obtained for food samples examined without prior enrichment and most results were negative. This rapid and simple assay provides a sensitive and specific means of screening drinking water or environmental water samples, as well as food samples, for the presence of Salmonella spp.

DNA Primers↗

Detection of low numbers of pathogenic Yersinia enterocolitica in environmental water and sewage samples by nested polymerase chain reaction.

Isolation of pathogenic Yersinia enterocolitica from water and sewage by traditional culture techniques is time-consuming and subsequent differentiation between pathogenic and non-pathogenic strains can be difficult and unreliable. A nested polymerase chain reaction (PCR) procedure was used for the detection of low numbers of Y. enterocolitica in spiked samples from natural surface sources with variable background flora ranging from oligotrophic water to sewage. Water and sewage samples were filtered and filters enriched overnight in a non-selective medium. Nested PCR conducted on enriched broth, prepared by use of a rapid and simple preparation step consisting of centrifugation, proteinase K treatment and boiling, enabled the detection of 8-17 cfu 100 ml-1 water with background levels of up to 8700 heterotrophic organisms ml-1 and 10,000 cfu coliform organisms 100 ml-1 water. The analysis can be completed within 2-3 d and should be a significant tool in monitoring environmental waters and drinking water sources for the presence of pathogenic Y. enterocolitica.

Environmental Monitoring↗