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Biomedical subjects

Michael G Stewart

Publications and source records attributed to Michael G Stewart.

At least 19 recordsLinked to original sources
PubMed2006

Manipulating Kv4.2 identifies a specific component of hippocampal pyramidal neuron A-current that depends upon Kv4.2 expression.

The somatodendritic A-current, I(SA), in hippocampal CA1 pyramidal neurons regulates the processing of synaptic inputs and the amplitude of back propagating action potentials into the dendritic tree, as well as the action potential firing properties at the soma. In this study, we have used RNA interference and over-expression to show that expression of the Kv4.2 gene specifically regulates the I(SA) component of A-current in these neurons. In dissociated hippocampal pyramidal neuron cultures, or organotypic cultured CA1 pyramidal neurons, the expression level of Kv4.2 is such that the I(SA) channels are maintained in the population at a peak conductance of approximately 950 pS/pF. Suppression of Kv4.2 transcripts in hippocampal pyramidal neurons using an RNA interference vector suppresses I(SA) current by 60% in 2 days, similar to the effect of expressing dominant-negative Kv4 channel constructs. Increasing the expression of Kv4.2 in these neurons increases the level of I(SA) to 170% of the normal set point without altering the biophysical properties. Our results establish a specific role for native Kv4.2 transcripts in forming and maintaining I(SA) current at characteristic levels in hippocampal pyramidal neurons.

Action Potentials↗
PubMed2006

Enhancement of long-term memory retention by Colostrinin in one-day-old chicks trained on a weak passive avoidance learning paradigm.

Colostrinin (CLN) is a biologically active proline-rich polypeptide which has therapeutic potential for the alleviation of memory deficits in age-related dementias in a number of human conditions, particularly Alzheimer's disease. To examine the efficacy of CLN in other species, day-old domestic chicks were used as a model system to study its effects on retention of memory for a single one-trial learning paradigm--avoidance of a bitter-tasting substance (methylanthranilate, MeA). Birds were presented with a bead coated with either a dilute (10%) solution of MeA or a bead coated with 100% MeA. Those trained on 100% MeA avoided pecking at a similar but dry bead 24 h later, thereby demonstrating long-term memory whereas chicks trained on the 10% solution pecked the bead at 24 h, indicating lack of long term memory for the task. However, when CLN was injected (i.c.) into a region known to be important in memory formation, the mesopallium intermediomediale (IMM), prior to training with 10% MeA, chicks exhibited strong memory retention at 24 h, similar to those trained on 100% MeA. Control chicks trained on 10% MeA but injected i.c. with a 10% saline solution did not show improvement in memory retention. Intraperitoneal (i.p.) injections of CLN were as effective as the i.c. route. These data extend the known efficacy of CLN from mammals demonstrating its widespread efficacy as a cognitive enhancer.

Animals↗
PubMed2006

Rhinosinusitis: developing guidance for clinical trials.

The Rhinosinusitis Initiative was developed by 5 national societies. The current guidance document is an expansion of the 2004 publication "Rhinosinusitis: Establishing definitions for clinical research and patient care" and provides templates for clinical trials in antimicrobial, anti-inflammatory, and symptom-relieving therapies for the following: (1) acute presumed bacterial rhinosinusitis, (2) chronic rhinosinusitis (CRS) without nasal polyps, (3) CRS with nasal polyps, and (4) classic allergic fungal rhinosinusitis. In addition to the templates for clinical trials and proposed study designs, the Rhinosinusitis Initiative has developed 6 appendices, which address (1) health outcomes, (2) nasal endoscopy and staging of CRS, (3) radiologic imaging, (4) microbiology, (5) laboratory measures, and (6) biostatistical methods.

Chronic Disease↗
PubMed2006

Rhinosinusitis: Developing guidance for clinical trials.

The Rhinosinusitis Initiative was developed by 5 national societies. The current guidance document is an expansion of the 2004 publication, "Rhinosinusitis: Establishing definitions for clinical research and patient care" and provides templates for clinical trials in antimicrobial, anti-inflammatory, and symptom-relieving therapies for the following: (1) acute presumed bacterial rhinosinusitis, (2) chronic rhinosinusitis (CRS) without nasal polyps, (3) CRS with nasal polyps, and (4) classic allergic fungal rhinosinusitis. In addition to the templates for clinical trials and proposed study designs, the Rhinosinusitis Initiative has developed 6 appendices, which address (1) health outcomes, (2) nasal endoscopy and staging of CRS, (3) radiologic imaging, (4) microbiology, (5) laboratory measures, and (6) biostatistical methods.

Chronic Disease↗
PubMed2006

Patient-controlled comparison of flexible endoscopic evaluation of swallowing with sensory testing (FEESST) and videofluoroscopy.

OBJECTIVE: The objective of this study was to compare the results of videofluoroscopy (VFS) with flexible endoscopic evaluation of swallowing with sensory testing (FEESST) in dysphagia testing. METHODS: The authors conducted a retrospective review of data collected over a 4-year period at a tertiary care medical center. The FEESST and VFS results for patients receiving both examinations within a 2-week period were compared with respect to swallowing function. Comparisons were categorized as full agreement, minor disagreement that would not result in a significant difference in diet recommendations, and major disagreement that would result in a significant difference in diet recommendations. Kappa with quadratic weighting was calculated to evaluate the inter-test agreement. RESULTS: Fifty-four patients met inclusion criteria and were reviewed. Forty-one percent of patients were not eating by mouth at the time of FEESST and the mean interval between the two examinations was 5 days. Laryngeal examination revealed edema/erythema in 93%, impaired pharyngeal squeeze in 66%, decreased laryngopharyngeal sensation in 82%, and absent laryngeal adductor reflex in 30%. FEESST with all consistencies revealed pooling in 89%, penetration in 83%, and aspiration in 65% of patients. VFS revealed pooling in 65%, penetration in 67%, and aspiration in 54% of patients. Comparison of FEESST and VFS revealed full agreement in 52%, minor disagreement in 13%, and major disagreement in 35% of patients. A weighted kappa value of 0.324 signified only "fair" agreement between the two tests. CONCLUSIONS: FEESST and VFS may not represent comparable tests of dysphagia. Further comparative studies of tests of swallowing function are required to determine the ideal approach to dysphagia testing.

Adult↗
PubMed2005

Mitochondria form a filamentous reticular network in hippocampal dendrites but are present as discrete bodies in axons: a three-dimensional ultrastructural study.

The fine structure of mitochondria and smooth endoplasmic reticulum (SER) was studied via electron microscopy in dendritic and axonal neuronal segments of hippocampal areas CA1, CA3, and dentate gyrus (DG) of both ground squirrels in normothermic and hibernating conditions, and rats. Ultrathin serial sections of approximately 60 nm (up to 150 per series) were taken and three-dimensional (3D) reconstructions made of dendritic segments, up to 36 microm in length. Mitochondria were demonstrated to be present in filamentous form in every dendrite examined, in each of the hippocampal regions studied, whether in rat or ground squirrel. In addition, apparent continuity between the outer mitochondrial membrane and that of SER was observed by 3D reconstructions of very ultrathin (20 nm) serial sections prepared from dendritic segments. It is believed that SER penetrate into the heads of thin and mushroom spines but mitochondria do not enter the heads of these types of spines in dentate gyrus or CA1 of either rat or ground squirrel. However, in CA3 we have shown here that mitochondria penetrate into the base of the large thorny excrescences. Mushroom dendritic spines (but not thin spines) contained puncta adherentia, formed between pre- and postsynaptic membranes. In contrast to dendrites, the mitochondrial population of axonal processes in the same hippocampal regions were found only in the form of discrete bodies no more than 3 microm in length. The issue of the likely function of this network in dendrites and its potential role in calcium movement is discussed.

Animals↗
PubMed2005

Quality of life and sleep study findings after adenotonsillectomy in children with obstructive sleep apnea.

OBJECTIVES: To assess polysomnogram (PSG) results and global and disease-specific quality of life (QOL) in children with obstructive sleep apnea (OSA), before and after adenotonsillectomy, and to assess the association between PSG findings and QOL. DESIGN: Prospective observational study. We performed overnight PSG using standardized techniques and assessed disease-specific and global QOL using validated instruments. Follow-up was assessed at 1 year. We compared QOL outcomes between children who underwent adenotonsillectomy and children who did not. SETTING: A large tertiary care children's hospital. PATIENTS: Children with sleep-disordered breathing who were suspected of having OSA. INTERVENTION: Adenotonsillectomy. MAIN OUTCOME MEASURES: We evaluated PSG parameters, disease-specific QOL, and global QOL. RESULTS: We enrolled 47 children, 31 of whom met PSG criteria for OSA. Disease-specific and global QOL were not significantly different between children with OSA and children without. Global QOL was significantly worse for children with OSA than healthy children on several subscales: general health perception, behavior, and parental impact-emotional. Children who underwent adenotonsillectomy had significant improvements in QOL scores and PSG parameters (apnea-hypopnea index, P = .004; minimum saturation, P = .004). We found significantly larger QOL changes in children who underwent surgery compared with children without surgery (subscales: infections, P = .01; airway, P = .002; swallowing, P = .02; and behavior, P = .03). No strong association was identified between QOL scores and PSG parameters. CONCLUSIONS: Children with OSA and sleep-disordered breathing have significantly worse QOL than healthy children. However, the association between PSG findings and QOL was only moderate. Children with OSA treated with adenotonsillectomy demonstrated large improvements in disease-specific and global QOL as well as PSG parameters.

Adenoidectomy↗
PubMed2005

The Cooperative Outcomes Group for ENT: a multicenter prospective cohort study on the effectiveness of medical and surgical treatment for patients with chronic rhinosinusitis.

OBJECTIVE: To assess outcomes for patients with chronic rhinosinusitis. STUDY DESIGN AND SETTING: Prospective, multicenter study; 31 otolaryngologists enrolled 276 adult patients with chronic rhinosinusitis; patients completed surveys at 3-month intervals, and physicians provided clinical and treatment data. The primary outcome measure was the Chronic Sinusitis Survey-Duration (CSS-D). RESULTS: One hundred seventeen adult patients completed 12-month follow-up. Most patients reported sinus symptoms lasting longer than 3 years (74%). Patients showed significant improvement (group P < 0.0001) in the CSS-D score at each follow-up interval. Baseline CSS-D ( P < 0.0001), surgical intervention ( P < 0.003), and Lund-McKay score ( P < 0.04) were predictive of clinical success in regression analysis. CONCLUSIONS: Patients referred to an otolaryngologist have a severe sinus illness. Treatment by an otolaryngologist was associated with significant improvement in sinus-related symptoms. SIGNIFICANCE: The study demonstrated the feasibility of multicenter outcome studies in chronic rhinosinusitis and generated testable hypotheses for future investigation. EBM RATING: C.

Adult↗
PubMed2005

The Cooperative Outcomes Group for ENT: a multicenter prospective cohort study on the outcomes of tympanostomy tubes for children with otitis media.

OBJECTIVE: Outcomes for patients with otitis media were assessed in this prospective, multicenter study. STUDY DESIGN AND SETTING: Thirty-one otolaryngologists enrolled 272 pediatric patients with otitis media; caregivers completed surveys at 3-month intervals, and clinical and treatment data was also collected. The Otitis Media 6 (OM-6) was the primary outcome measure. RESULTS: One hundred seventy-seven patients (mean age 2.0 years) completed 3-month follow-up. One hundred thirty-seven patients underwent tympanostomy tube placement. Large improvements in disease-specific quality of life (QOL) were seen up to 9 months of follow-up. Baseline OM-6 score was the best predictor of clinical success in regression modeling. CONCLUSIONS: Patients referred to an otolaryngologist for treatment of otitis media see large improvements in disease-specific QOL regardless of treatment rendered. SIGNIFICANCE: The study demonstrates the feasibility of multicenter outcomes studies and confirms appropriate triage of patients with otitis media into surgical versus medical interventions. EBM RATING: C.

Child↗
PubMed2005

The contemporary approach to diagnosis and management of peritonsillar abscess.

PURPOSE OF REVIEW: Peritonsillar abscess is a common problem, but some aspects of diagnosis and management remain controversial. We review the recent literature on peritonsillar abscess. RECENT FINDINGS: Intraoral ultrasound can be a helpful diagnostic tool for peritonsillar abscess. For management, needle aspiration, incision and drainage, and quinsy tonsillectomy all yield successful results. Recent reviews have still not established that one treatment is consistently preferred. A randomized, placebo-controlled trail found that the use of intravenous steroids seems to reduce many symptoms, when used along with abscess drainage. SUMMARY: The use of steroids may be beneficial in the treatment of peritonsillar abscess, and different techniques for abscess drainage are still used around the world, with consistently good results.

Anti-Inflammatory Agents↗
PubMed2004

Expression of long-term potentiation in aged rats involves perforated synapses but dendritic spine branching results from high-frequency stimulation alone.

Evidence for morphological substrates of long-term changes in synaptic efficacy is controversial, partly because it is difficult to employ an unambiguous control. We have used a high-frequency stimulation protocol in vivo to induce long-term potentiation (LTP) in the hippocampal dentate gyrus of aged (22-month-old) rats and have found a clear distinction between animals that sustain LTP and those that fail to sustain it. The "failure group" was used as a specific/"like-with-like" control for morphological changes associated with the expression of LTP per se. Quantitative optical and electron microscopy was used to analyze large populations of dendritic spines and excitatory perforant path synapses; LTP was found to be associated with an increase in numbers of segmented (perforated) postsynaptic densities in spine synapses. In contrast, an increase in the number of branched spines appears to result from high-frequency stimulation alone. These data shed light on the current controversy about the expression mechanism of LTP.

Aging↗
PubMed2004

Inhibiting effect of D1, but not D2 antagonist administered to the striatum on retention of passive avoidance in the chick.

The avian lobus parolfactorius, equivalent to the medial striatum (caudate-putamen) of mammals, has been shown to be of crucial importance in passive avoidance training in day-old domestic chicks, where the aversive stimulus is the bitter tasting substance methylanthranilate. Here we report that the specific D1 antagonist SCH23390, injected into the lobus parolfactorius of day-old chicks (Gallus domesticus) prior to training, impaired performance on testing 30min post-training at low doses (0.5 and 25nmol). Sulpiride, a D2 antagonist, had no significant effect on performance in comparable doses. The early D1 activation may signify an essential mechanism leading to storage itself or to the canalisation of the relevant association to a permanent store.

Animals↗
PubMed2004

Development and validation of the Nasal Obstruction Symptom Evaluation (NOSE) scale.

OBJECTIVE: The study goal was to validate a disease-specific health status instrument for use in patients with nasal obstruction.Design, settings, and patients The study consisted of a prospective instrument validation conducted at 4 academic medical centers with 32 adults with nasal septal deformity. METHODS: Prospective instrument validation occurred in 2 stages. Stage 1 was the development of a preliminary (alpha-version) instrument of potential items. Stage 2 was a test of the alpha-version for item performance, internal consistency, and test-retest reliability; construct, discriminant, criterion validity, and responsiveness; and creation of the final instrument. RESULTS: Items with poor performance were eliminated from the alpha-version instrument. In testing the final instrument, test-retest reliability was adequate at 0.702; internal consistency reliability was also adequate at 0.785. Validity was confirmed using correlation and comparison analysis, and response sensitivity was excellent. CONCLUSIONS: The Nasal Obstruction Symptom Evaluation Scale is a valid, reliable, and responsive instrument that is brief and easy to complete and has potential use for outcomes studies in adults with nasal obstruction.

Adult↗
PubMed2004

Outcomes after nasal septoplasty: results from the Nasal Obstruction Septoplasty Effectiveness (NOSE) study.

OBJECTIVE: Our goal was to assess disease-specific quality of life outcomes after nasal septoplasty in adults with nasal obstruction. DESIGN, SETTINGS, AND PATIENTS: We conducted a prospective observational outcomes multicenter study with 14 sites and 16 investigators, including private practice and academic settings. Patients had had septal deviation and symptomatic nasal obstruction for at least 3 months, and medical management had failed. METHODS: Patients with septal deviation completed a validated outcomes instrument (the Nasal Obstruction Septoplasty Effectiveness [NOSE] scale) before and 3 and 6 months after septoplasty, with or without partial turbinectomy. RESULTS: Fifty-nine patients underwent surgery; there was a significant improvement in mean NOSE score at 3 months after septoplasty (67.5 versus 23.1, P < 0.0001), and this improvement was unchanged at 6 months. Patient satisfaction was very high, and patients used significantly fewer nasal medications. CONCLUSIONS: In patients with septal deformity, nasal septoplasty results in significant improvement in disease-specific quality of life, high patient satisfaction, and decreased medication use.

Adult↗
PubMed2004

Ototoxicity of ototopical antibiotic drops in humans.

OBJECTIVE: We sought to determine the incidence of injury to the cochlea or vestibular system from the use of ototopic antibiotic ear drops. STUDY DESIGN: We conducted a MEDLINE search of the published literature from 1966 to the present using the search items of "ototopic antibiotics," "ototopic drops," "antibiotic resistance," and others to identify pertinent articles. These articles were reviewed and graded according to evidence quality. Forty-four articles were found; 27 articles were considered appropriate for review and 14 of these articles were thought to warrant further extensive review. The latter 14 articles dealt directly with the evaluation of either hearing loss or changes in vestibular function after the use of ototopic ear drops. We eliminated studies that did not consider hearing or vestibular function. We considered only articles in the English language, eliminating articles that not address the ototoxicity of ototopical ear drops. RESULTS: Most of these articles were in the level 3 to 3b category. Two of the articles were in the 1b category, evaluating evidence-based studies. An article that reviewed case reports of ototopical ototoxicity and a survey article are included in this study, as case reports of ototopical ototoxicity and survey articles. CONCLUSION: We found a total of 54 cases of gentamicin vestibular toxicity and, in 24 of these patients, cochlear toxicity was also documented. Our review also found 11 cases of cochlear and 2 cases of vestibular toxicity in neomycin-based ear drops.

Administration, Topical↗
PubMed2004

Animal ototoxicity of topical antibiotics and the relevance to clinical treatment of human subjects.

OBJECTIVE: The objective of this study was to systematically review the literature on animal ototoxicity from ototopical medications. A secondary objective was to assess the relevance of animal data to the use of ototopical drops in clinical situations involving humans. STUDY DESIGN: We performed a MEDLINE search of the published literature using appropriate search terms to identify pertinent articles, which were reviewed, summarized, and tabulated. RESULTS: One hundred seventy-three articles were reviewed; 61 articles were appropriate to the study question and were further analyzed. CONCLUSIONS: Virtually all studies demonstrate that aminoglycoside antibiotics, when applied topically into the middle ear space, are ototoxic in experimental animals.

Administration, Topical↗
PubMed2004

The development of antibiotic resistant organisms with the use of ototopical medications.

OBJECTIVE: There is growing concern over the use of systemic antibiotics and the development of bacterial resistance. The question remains as to whether ototopical medications may also promote antibiotic-resistant organisms, either on a local level (in the ear) or in other areas of the aerodigestive tract. We performed an evidence-based review to answer the following clinical question, "Do antibiotic ototopical medications induce antibiotic resistant organisms?" STUDY DESIGN: We performed a MEDLINE search of the published literature from 1966 to the present. We used appropriate search terms such as "ototopical antibiotics," "ototopical drops," "antibiotic resistance," "topical antibiotics and otitis externa," "otitis externa and treatment," "otitis externa and antibiotic drops," "otitis externa and ototopical drops," "otitis media," "otitis media and treatment," "otitis media and antibiotic drops," "chronic suppurative otitis media," "chronic suppurative otitis media and treatment," "chronic suppurative otitis media and antibiotic drops," " otitis externa and resistant organisms," "otitis media and resistant organisms," "chronic suppurative otitis media and resistant organisms," "ophthalmic antibiotic drops," "draining ear," "P.E. tube otorrhea," "pressure equalizing tube otorrhea," "pressure equalizing tube otorrhea and treatment," and "pressure equalizing tube otorrhea and ototopical therapy" to identify pertinent articles. These articles were reviewed and graded according to the evidence quality. RESULTS: After an initial screening of over 2,500 articles, 38 articles were analyzed further; of these, 11 were determined to warrant extensive review. Eight articles evaluated chronic suppurative otitis media; 2, otitis externa; and 1, post-tympanostomy tube otorrhea, whereas 3 others studied systemic absorption. Of the 8 chronic suppurative otitis media studies, there were thought to be 5 grade 2B studies, 1 grade 1B study, and 1 grade 2C study. These studies did not demonstrate a propensity for the development of resistant organisms. No study answered the question as to whether resistance to systemic antibiotics might occur in otitis externa. CONCLUSIONS: Overall grade B evidence seems to indicate that no significant antibiotic resistance develops from the use of ototopical antibiotic treatment.

Acute Disease↗