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Biomedical subjects

D B Mitchell

Publications and source records attributed to D B Mitchell.

At least 19 recordsLinked to original sources
PubMed2001

Major complications and consent prior to endoscopic sinus surgery.

The endonasal endoscopic approach to the paranasal sinuses is no longer exclusively practised by a small number of dedicated super-specialists and has gained widespread acceptance in the UK. We have audited the practice of the Consultant members of the BAO-HNS via a confidential postal questionnaire with regards to the consent of their patients prior to surgery, and to the complications they have experienced. The overall rate of complications following endoscopic sinus surgery (ESS) was 0.69%, with the incidence of major complications 0.25% and of minor complications 0.44%. Wide variations in the practice of informed consent were found to exist, and this is discussed with reference to a suggested template for preoperative discussion with the patient.

Chronic Disease↗
PubMed2001

Bulbar presentations of myasthenia gravis in the elderly patient.

We report on three cases of patients whose primary symptoms of myasthenia gravis were related to the upper aerodigestive tract. Symptoms had been present unrecognized in all patients for up to three years, and one patient subsequently developed a myasthenic crisis. We highlight the clinical features of myasthenia gravis to allow its prompt recognition in patients presenting to the ENT surgeon or physician.

Aged↗
PubMed2001

Malakoplakia of the oropharynx.

We present a case of malakoplakia presenting as a lesion in the oropharynx of an elderly smoker. In this case a clinical diagnosis of carcinoma of the pharynx was made, biopsy revealed the nature of the lesion and management was radically altered.

Aged↗
PubMed2001

Respiratory syncytial virus infection does not increase allergen-induced type 2 cytokine production, yet increases airway hyperresponsiveness in mice.

Severe respiratory syncytial virus (RSV)-induced disease is associated with childhood asthma and atopy. We combined murine models of allergen-sensitization and RSV infection to explore the interaction of allergic and virus-induced airway inflammation and its impact on airway hyperresponsiveness (AHR). We found that RSV infection during ova-sensitization (OVA/RSV) increased and prolonged AHR compared to mice only RSV-infected (RSV) or ova-sensitized (OVA). AHR is known to be associated with an increase in Type 2 cytokines (IL-4, IL-5, and IL-13) in allergen-sensitized mice. Therefore, we hypothesized that RSV-induced enhancement of AHR was a result of potentiating the Type 2 cytokine profile promoted by ova-sensitization. Surprisingly, we found that Type 2 cytokines induced by ova-sensitization were not increased by RSV infection despite the increase in AHR, and in some cases were diminished. RNAse protection assay revealed no difference in IL-4 and IL-5 mRNA levels between the OVA and OVA/RSV groups, and IL-13 mRNA was significantly decreased in the OVA/RSV mice compared to the OVA group. Flow cytometric analysis of Type 2 cytokines demonstrated the same frequency of IL-4 and IL-5 production in lung-derived T lymphocytes from the OVA/RSV and OVA groups. Direct cytokine ELISA measurements of lung supernatant showed the level of IL-13 was significantly decreased in the OVA/RSV group compared to OVA mice, while there was no difference in either IL-4 or IL-5 between these two groups. These data indicate that the enhanced and prolonged AHR caused by the interaction of allergic airway inflammation and virus-induced immune responses is a complex process that can not be explained simply by augmented production of Type 2 cytokines.

Allergens↗
PubMed2000

Respiratory syncytial virus (RSV)-induced airway hyperresponsiveness in allergically sensitized mice is inhibited by live RSV and exacerbated by formalin-inactivated RSV.

Respiratory syncytial virus (RSV)-induced disease is associated with recurrent episodes of wheezing in children, and an effective vaccine currently is not available. The use of 2 immunizations (a formalin-inactivated, alum-precipitated RSV vaccine [FI-RSV] given intramuscularly and live RSV given intranasally [LVIN]), with a control immunization, were compared in a well-characterized model of RSV challenge, with or without concomitant allergic sensitization with ovalbumin. FI-RSV caused a significant increase in airway hyperresponsiveness in mice after RSV infection during allergic sensitization, and this was associated with an increase in type 2 cytokine production. In contrast, immunization with LVIN did not change type 2 cytokine production and protected against RSV-induced airway hyperresponsiveness in the setting of allergic sensitization. This study suggests that immune modulation with RSV vaccination can have profound effects on RSV-induced airway disease and that prevention of airway hyperresponsiveness is an important end point in vaccine development.

Administration, Intranasal↗
PubMed2000

Pectoralis major muscle and tendon tears: diagnosis and grading using magnetic resonance imaging.

OBJECTIVE: To assess the accuracy and utility of magnetic resonance (MR) imaging in the detection and grading of pectoralis major muscle and tendon tears. DESIGN AND PATIENTS: A retrospective review was carried out of 10 patients referred for MR imaging for suspected pectoralis muscle injury and possible operative therapy. The pectoralis muscle and tendon were imaged using thin (3-4 mm) axial sections with a variety of sequences combined for anatomical delineation (T1-weighted SE or PD SE) and fluid detection (T2-weighted SE, T2-weighted FSE with fat suppression, or STIR). Surgical correlation was available in six patients. Clinical follow-up was available in four patients treated by nonoperative therapy. RESULTS: MR imaging identified five complete tears, four partial tears and one normal tendon. One complete and one partial tear were at the myotendinous junction. The remaining seven injuries were at the enthesis. Surgical correlation consisted of five complete tears and one partial tear. One complete and one partial tear were at the myotendinous junction with the remaining four complete tears at the enthesis. The MR interpretation and surgical findings were in agreement in all six cases. All four patients treated with nonoperative therapy demonstrated improvement at a clinical follow-up examination, with restoration of function and strength consistent with a healed prior partial injury. CONCLUSION: MR imaging is accurate and useful in detecting and grading tears involving the pectoralis major muscle and tendon, facilitating the identification of patients with complete tears who are candidates for operative therapy.

Adolescent↗
PubMed2000

Cyclooxygenase inhibition increases interleukin 5 and interleukin 13 production and airway hyperresponsiveness in allergic mice.

The immunomodulatory role of arachidonic acid metabolites in allergic sensitization is undefined. Prostaglandin E(2) (PGE(2)), a product of arachidonic acid metabolism through the cyclooxygenase pathway, has been reported to favor Type 2-like cytokine secretion profiles in murine and human CD4(+) T cells by inhibiting the production of Type 1-associated cytokines. On the basis of these in vitro data, we hypothesized that indomethacin, a nonselective cyclooxygenase inhibitor, would diminish allergen-induced production of Type 2 cytokines in mice, and protect against airway hyperresponsiveness (AHR) to methacholine. We found that ovalbumin-sensitized mice that were treated with indomethacin (OVA-indomethacin mice) had significantly greater AHR (p < 0.05) and higher levels of IL-5 (176 +/- 52 versus 66 +/- 4 pg/ml) and IL-13 (1,226 +/- 279 versus 475 +/- 65 pg/ml) in lung supernatants than mice sensitized with ovalbumin alone (OVA mice), while levels of IL-4 and serum IgE were not different. Lung mRNA expression of the C-C chemokine MCP-1 was increased in OVA-indomethacin mice, while there was no difference between the two groups in lung mRNA expression of eotaxin, MIP-1alpha, MIP-1beta, or MIP-2. Histologic examination revealed greater pulmonary interstitial eosinophilia in OVA-indomethacin mice as well. Contrary to our expectations, we conclude that in the BALB/c mouse, cyclooxygenase inhibition during allergen sensitization increases AHR, production of IL-5 and IL-13, and interstitial eosinophilia.

Animals↗
PubMed1999

Preferential role for NF-kappa B/Rel signaling in the type 1 but not type 2 T cell-dependent immune response in vivo.

T cell function is a critical determinant of immune responses as well as susceptibility to allergic diseases. Activated T cells can differentiate into effectors whose cytokine profile is limited to type 1 (IFN-gamma-dominant) or type 2 (IL-4-, IL-5-dominant) patterns. To investigate mechanisms that connect extracellular stimuli with the regulation of effector T cell function, we have measured immune responses of transgenic mice whose NF-kappa B/Rel signaling pathway is inhibited in T cells. Surprisingly, these mice developed type 2 T cell-dependent responses (IgE and eosinophil recruitment) in a model of allergic pulmonary inflammation. In contrast, type 1 T cell responses were severely impaired, as evidenced by markedly diminished delayed-type hypersensitivity responses, IFN-gamma production, and Ag-specific IgG2a levels. Taken together, these data indicate that inhibition of NF-kappa B can lead to preferential impairment of type 1 as compared with type 2 T cell-dependent responses.

Animals↗
PubMed1999

Respiratory syncytial virus infection prolongs methacholine-induced airway hyperresponsiveness in ovalbumin-sensitized mice.

Severe respiratory syncytial virus (RSV)-induced disease is associated with childhood asthma and atopy. We combined models of allergen sensitization and RSV infection to begin exploring the immunologic interactions between allergic and virus-induced airway inflammation and its impact on airway hypersensitivity. Airway resistance was measured after methacholine challenge in tracheally intubated mice by whole body plethysmography. Lung inflammation was assessed by bronchoalveolar lavage (BAL) and histopathology. RSV infection alone did not cause significant airway hyperresponsiveness (AHR) to methacholine. Ovalbumin (OVA)-induced AHR lasted only a few days past the discontinuance of OVA aerosol in mice that were ovalbumin sensitized and mock infected. In contrast, OVA-sensitized mice infected with RSV during the OVA aerosol treatments (OVA/RSV) had AHR for more than 2 weeks after infection. However, 2 weeks after either RSV or mock infection, OVA/RSV mice had significantly more lymphocytes found during BAL than OVA mice, whereas the OVA and OVA/RSV groups had the same number of eosinophils. Histopathologic analysis confirmed an increased inflammation in the lungs of OVA/RSV mice compared with OVA mice. In addition, OVA/RSV mice had a more widespread distribution of mucus in their airways with increased amounts of intraluminal mucus pools compared with the other groups. Thus, prolonged AHR in RSV-infected mice during ovalbumin-sensitization correlates with increased numbers of lymphocytes in BAL fluid, increased lung inflammation, and mucus deposition in the airways, but not with airway eosinophilia. A further understanding of the immunologic consequences of combined allergic and virus-induced airway inflammation will impact the management of diseases associated with airway hyperreactivity.

Animals↗
PubMed1998

Laser assisted uvulopalatoplasty: six and eighteen month results.

Our ongoing evaluation of the results of laser assisted uvulopalatoplasty (LAUP) for snoring is presented. Follow-up between 18 and 24 months post-treatment completion, of patients with a successful result at six months, reveals that 22 per cent of these patients suffer failure of snoring control between these two evaluation points. This equates to an overall success rate at this time of 55 per cent. LAUP, like other surgical remedies for snoring, has a continued relapse rate. This must be considered when counselling patients.

Adult↗
PubMed1997

Cloning of the phytases from Emericella nidulans and the thermophilic fungus Talaromyces thermophilus.

Phytases (EC 3.1.3.8) belong to the family of histidine acid phosphatases. We have cloned the phytases of the fungi Emericella nidulans and Talaromyces thermophilus. The putative enzyme encoded by the E. nidulans sequence consists of 463 amino acids and has a Mr of 51785. The protein deduced from the T. thermophilus sequence consists of 466 amino acids corresponding to a Mr of 51450. Both predicted amino acid sequences exhibited high identity (48% to 67%) to known phytases. This high level of identity allowed the modelling of all available fungal phytases based on the three-dimensional structure coordinates of the Aspergillus niger phytase. By this approach we identified 21 amino acids which are conserved in fungal phyA phytases and are part of the residues forming the substrate pocket. Furthermore, potential glycosylation sites were identified and compared between the aforementioned phytases and the A. niger phytase.

6-Phytase↗
PubMed1996

A new approach to the safety assessment of pharmaceutical excipients. The Safety Committee of the International Pharmaceutical Excipients Council.

This article presents a set of proposed guidelines for the safety assessment of new pharmaceutical excipients. These guidelines were developed by the Safety Committee of the International Pharmaceutical Excipients Council and represent a new, scientifically based approach to establishing conditions for the safe use of proposed pharmaceutical excipients utilizing various routes of human exposure. They are based upon the best currently available toxicological science and have taken the deliberations of the International Conference on Harmonization into consideration. These guidelines were developed because there are no regulatory agency guidelines currently available which specifically address the toxicological testing of a material intended for use as an excipient in pharmaceutical preparations. Only materials which have been previously permitted for use in a pharmaceutical preparation or which have been permitted for use in foods may be considered safe under current practices. If implemented, these guidelines should expedite the review of a proposed new excipient by regulatory agencies.

Chemistry, Pharmaceutical↗
PubMed1996

Single and multiple test repetition priming in implicit memory.

Using a picture naming task, we compared the magnitude of repetition priming after one prior study episode (single test priming) versus multiple prior study presentations (multiple test priming). Pictures were repeated either one, two, or three times, and the interval between tests was either several minutes (blocked test) or one week (spaced test). Priming increased with additional prior presentations (beyond one) in the multiple test format. In addition, single test priming decreased within one hour after initial exposure, with little change from one hour to two weeks. Priming was unaffected by a simultaneous recognition task, suggesting that picture naming is an implicit task relatively immune from explicit memory contamination.

Humans↗
PubMed1996

The juvenile court: a view from the bench.

This article describes the changing role of the juvenile court from the perspective of an urban juvenile court judge. The author's experiences as the administrative judge for Baltimore City's juvenile court address typical current juvenile court dilemmas such as lack of funding, physical space that is inadequate for the needs of the court and those it serves, and limited dispositional options for juvenile offenders. Examples of effective judicial advocacy are presented, as are suggestions for positive court reform.

Adolescent↗
PubMed1994

A reevaluation of semantic versus nonsemantic processing in implicit memory.

A number of investigations have purported to demonstrate that semantic processing does not produce a memorial advantage over nonsemantic processing on implicit tests, as contrasted with the typical advantage of semantic over nonsemantic processing on explicit tests. A review of 166 outcomes from 38 studies that have manipulated processing on implicit tests reveals that on 131 occasions (79%), priming was greater following semantic than it was following nonsemantic processing. This difference was found in both perceptual and conceptual implicit memory tests, as well as in within- and between-subjects designs. It suggests that implicit tests reflect the involvement of both conceptual and perceptual processes. Although explicit contamination may account for some of the processing difference in implicit tests, the pervasiveness of the phenomenon, especially in perceptual implicit tests, makes it an unlikely account for the entire effect.

Attention↗