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Biomedical subjects

Michael Wall

Publications and source records attributed to Michael Wall.

At least 19 recordsLinked to original sources
PubMed2024

Myoferlin: A Potential Marker of Response to Radiation Therapy and Survival in Locally Advanced Rectal Cancer.

PURPOSE: Patients with locally advanced rectal cancer often require neoadjuvant chemoradiation therapy to downstage the disease, but the response is variable with no predictive biomarkers. We have previously revealed through proteomic profiling that myoferlin is associated with response to radiation therapy. The aims of this study were to further validate this finding and explore the potential for myoferlin to act as a prognostic and/or therapeutic target. METHODS AND MATERIALS: Immunohistochemical analysis of a tissue microarray (TMA) for 111 patients was used to validate the initial proteomic findings. Manipulation of myoferlin was achieved using small interfering RNA, a small molecular inhibitor (wj460), and a CRISPR-Cas9 knockout cell line. Radiosensitization after treatment was assessed using 2-dimensional clonogenic assays, 3-dimensional spheroid models, and patient-derived organoids. Underlying mechanisms were investigated using electrophoresis, immunofluorescence, and immunoblotting. RESULTS: Analysis of both the diagnostic biopsy and tumor resection samples confirmed that low myoferlin expression correlated with a good response to neoadjuvant long-course chemoradiation therapy. High myoferlin expression was associated with spread to local lymph nodes and worse 5-year survival (P = .01; hazard ratio, 3.5; 95% CI, 1.27-10.04). This was externally validated using the Stratification in Colorectal Cancer database. Quantification of myoferlin using immunoblotting in immortalized colorectal cancer cell lines and organoids demonstrated that high myoferlin expression was associated with increased radioresistance. Biological and pharmacologic manipulation of myoferlin resulted in significantly increased radiosensitivity across all cell lines in 2-dimensional and 3-dimensional models. After irradiation, myoferlin knockdown cells had a significantly impaired ability to repair DNA double-strand breaks. This appeared to be mediated via nonhomologous end-joining. CONCLUSIONS: We have confirmed that high expression of myoferlin in rectal cancer is associated with poor response to neoadjuvant therapy and worse long-term survival. Furthermore, the manipulation of myoferlin led to increased radiosensitivity in vitro. This suggests that myoferlin could be targeted to enhance the sensitivity of patients with rectal cancer to radiation therapy, and further work is required.

Humans↗
PubMed2006

Prevalence of a normal C-reactive protein with an elevated erythrocyte sedimentation rate in biopsy-proven giant cell arteritis.

OBJECTIVE: The erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are laboratory tests that have been said to have a strong correlation with a positive temporal artery biopsy in patients with suspected giant cell arteritis (GCA). Published reports suggest that the CRP is a more sensitive diagnostic indicator of GCA and can be elevated when the ESR is normal. It is also clear that the CRP and ESR can both be normal or both be elevated in patients with biopsy-proven GCA and that the CRP can be elevated when the ESR is normal. The purpose of this study was to ascertain if the CRP can be normal when the ESR is elevated in biopsy-proven GCA. DESIGN: Retrospective, longitudinal, comparative study. PARTICIPANTS: One hundred nineteen patients from 6 major tertiary-care university-affiliated medical centers. METHODS: The charts from 119 patients with temporal artery biopsies positive for GCA were reviewed for age, gender, pretreatment ESR, and pretreatment CRP. MAIN OUTCOME MEASURES: The ESR in millimeters per hour Westergren was graded as normal or abnormal based on 2 validated formulas. The CRP was graded as normal or abnormal based on established criteria set forth in the literature as well as at The Johns Hopkins Hematology laboratory. RESULTS: In this study, the ESR had a sensitivity of 76% to 86%, depending on which of 2 formulas were used, whereas an elevated CRP had a sensitivity of 97.5%. The sensitivity of the ESR and CRP together was 99%. Only 1 of the 119 patients (0.8%) presented with a normal ESR and normal CRP (double false negative); 2 patients (1.7%) had a normal CRP despite an elevated ESR according to both formulas. CONCLUSION: Although most patients with GCA have both an elevated ESR and CRP, there can be nonconcordance of the 2 blood tests. Although such nonconcordance is most often a normal ESR but an elevated CRP, the finding of an elevated ESR and a normal CRP also is consistent with GCA. The use of both tests provides a slightly greater sensitivity for the diagnosis of GCA than the use of either test alone.

Aged↗
PubMed2006

Topical ciprofloxacin/dexamethasone superior to oral amoxicillin/clavulanic acid in acute otitis media with otorrhea through tympanostomy tubes.

OBJECTIVE: This study was a comparison of topical ciprofloxacin/dexamethasone otic suspension to oral amoxicillin/clavulanic acid suspension in children with acute otitis media with otorrhea through tympanostomy tubes. METHODS: This was a randomized, observer-masked, parallel-group, multicenter trial of topical ciprofloxacin/dexamethasone otic suspension versus amoxicillin/clavulanic acid suspension in 80 children aged 6 months to 12 years with acute otitis media with otorrhea through tympanostomy tubes of < or = 3 weeks' duration and visible otorrhea. Patients were randomly assigned to receive either 4 drops of topical ciprofloxacin 0.3%/dexamethasone 0.1% (Ciprodex Sterile Otic Suspension) into the affected ear(s) twice daily for 7 days or 600 mg of amoxicillin/42.9 mg of clavulanic acid oral suspension (Augmentin ES-600 Oral Suspension) every 12 hours for 10 days. Clinical signs and symptoms of acute otitis media with otorrhea through tympanostomy tubes were evaluated on days 1 (baseline), 3, 11 (end-of-therapy), and 18 (test-of-cure), and twice-daily assessments of otorrhea were recorded in patient diaries. RESULTS: The median time to cessation of otorrhea was significantly shorter with ciprofloxacin/dexamethasone otic suspension than with amoxicillin/clavulanic acid suspension (4.0 vs 7.0 days; n = 79). This resulted in significantly more clinical cures at the test-of-cure visit (85% vs 59%, respectively). Frequent adverse events (> 3%) related to ciprofloxacin/dexamethasone otic suspension included ear pain (5.1%) and related to amoxicillin/clavulanic acid suspension included diarrhea (19.5%), dermatitis (7.3%), and gastroenteritis (4.9%). CONCLUSIONS: Topical otic treatment with ciprofloxacin/dexamethasone otic suspension is superior to treatment with oral amoxicillin/clavulanic acid suspension and results in more clinical cures and earlier cessation of otorrhea with fewer adverse effects in children with acute otitis media with otorrhea through tympanostomy tubes.

Acute Disease↗
PubMed2006

IM interferon beta-1a delays definite multiple sclerosis 5 years after a first demyelinating event.

BACKGROUND: The Controlled High Risk Subjects Avonex Multiple Sclerosis Prevention Study (CHAMPS) showed that IM interferon beta-1a (IFNbeta-1a) significantly slows the rate of development of clinically definite multiple sclerosis (CDMS) over 2 years in high-risk patients who experience a first clinical demyelinating event. This report highlights the primary results of a 5-year, open-label extension of CHAMPS (the Controlled High Risk Avonex Multiple Sclerosis Prevention Study in Ongoing Neurologic Surveillance [CHAMPIONS Study]). OBJECTIVE: To determine if the benefits of IFNbeta-1a observed in CHAMPS are sustained for up to 5 years. METHODS: CHAMPS patients at participating CHAMPIONS sites were enrolled in the study. All patients were offered, but not required to take, IFNbeta-1a 30 microg IM once weekly for up to 5 years (from CHAMPS randomization). Patients who received placebo in CHAMPS were considered the delayed treatment (DT) group, and patients who received IFNbeta-1a in CHAMPS were considered the immediate treatment (IT) group. The primary outcome measure was the rate of development of CDMS. Additional outcomes included disease state classification at 5 years, annualized relapse rates, disability level at 5 years (Expanded Disability Status Scale), and MRI measures at 5 years. RESULTS: Fifty-three percent (203/383) of patients enrolled in CHAMPIONS (n = 100, IT group; n = 103, DT group) and 64% (32/50) of CHAMPS study sites participated in CHAMPIONS. The median time to initiation of IFNbeta-1a therapy in the DT group was 29 months. The cumulative probability of development of CDMS was significantly lower in the IT group compared with the DT group (5-year incidence 36 +/- 9 vs 49 +/- 10%; p = 0.03). Multivariate analysis suggested that the only factors independently associated with an increased rate of development of CDMS were randomization to the DT group and younger age at onset of neurologic symptoms. Few patients in either group developed major disability within 5 years. CONCLUSIONS: These results support the use of IM interferon beta-1a after a first clinical demyelinating event and indicate that there may be modest beneficial effects of immediate treatment compared with delayed initiation of treatment.

Adjuvants, Immunologic↗
PubMed2006

Subretinal neovascular membrane in idiopathic intracranial hypertension.

PURPOSE: To define the prevalence, natural history, treatment, and prognosis of papilledema-related juxtapapillary subretinal neovascular membranes (SRNVMs). DESIGN: Retrospective observational case series. METHODS: We conducted a retrospective chart review. RESULTS: Of 1140 cases of idiopathic intracranial hypertension, six patients had juxtapapillary SRNVM. Three patients were observed, and their final visual acuities were 20/20, 20/50, and 20/200. Three SRNVM involved the fovea; two of the cases were treated with argon laser therapy, and one case was treated with photodynamic therapy. CONCLUSION: SRNVM in idiopathic intracranial hypertension is rare (0.53%). Most cases of juxtapapillary SRNVM are self-limited and regress, can be observed, and have a favorable visual prognosis. The progression of the SRNVM ophthalmoscopically or angiographically toward the fovea, however, might be an indication for laser treatment. Once subfoveal extension occurs, the visual outcome tends to be unfavorable. No patients had recurrence of SRNVM after the resolution of the papilledema.

Acetazolamide↗
PubMed2006

Effects of ototopic steroid and NSAIDS in clearing middle ear effusion in an animal model.

OBJECTIVE: A model of otitis media with effusion (OME) has been developed in the Sprague-Dawley (SD) rat. This model was used to study the effects of an ototopic steroid and nonsteroidal anti-inflammatory drug (NSAID) on lipopolysaccharide (LPS)-induced OME. STUDY DESIGN: Twenty-six rats were randomized into 4 groups: saline solution, LPS, NSAID + LPS, and steroids + LPS. Test substance was injected into the middle ear at 0, 2, and 4 hours. The effusion was collected at 2, 4, and 6 hours. Statistical analysis of effusion volume and albumin concentration was performed. RESULTS: The LPS group demonstrated statistically significant increase in both effusion volume and albumin concentration compared with saline solution. Intergroup comparison revealed significantly less effusion volume in the steroid group and less albumin concentration in the NSAID group when compared with the LPS group. CONCLUSIONS: Transtympanic steroid reduced LPS induced middle ear effusion while NSAID reduced albumin concentration in the rat model. SIGNIFICANCE: Our results lend support to the current use of anti-inflammatory ototopicals in the treatment of inflammatory middle ear disease.

Animals↗
PubMed2006

Safety and efficacy of Sofenz ceruminolytic solution.

We conducted an open-label study of 109 untreated patients who had excessive or impacted cerumen. Our goal was to evaluate the safety and efficacy of Sofenz Cerumenolytic Solution, a methyltrypsin-containing earwax removal solution. Each patient's external auditory canal was filled with Sofenz for 15 minutes. The primary measure of efficacy--visibility of the tympanic membrane--was assessed after the solution had been drained from the canal and again after the canal had been irrigated with lukewarm water. If the tympanic membrane was not completely visible following either application, the procedure was repeated. A safety examination was conducted 1 to 3 days after treatment. Secondary outcomes measures included relief of otologic symptoms (e.g., hearing loss, tinnitus, etc.) and patients'overall satisfaction with treatment. Immediately after treatment, we found that the external auditory canal was completely visible in 81 patients (74.3%) after 1 application of Sofenz and subsequent irrigation, and in 98 patients (89.9%) after 2 applications of each. At the safety follow-up visit, we determined that the number of otologic symptoms had declined by 93.2%. A self-reported assessment completed by each patient following the procedure revealed a high degree of satisfaction with treatment. A total of 58 adverse events were reported, but only 16 were directly related to treatment, and all were transient and either mild or moderate. We conclude that 1 or 2 applications of Sofenz followed by irrigation with lukewarm water is a safe, well-tolerated, and effective treatment for excessive or impacted cerumen in the external auditory canal.

Administration, Topical↗
PubMed2005

Do female garter snakes evade males to avoid harassment or to enhance mate quality?

Females of many species behave in ways that make it difficult for males to locate, court, and inseminate them. Two hypotheses have been advanced to explain such behavior: either a female thereby minimizes costs of harassment (sexual conflict model) or by playing "hard to get" she discourages inferior suitors (indirect mate choice model). Our studies of garter snakes (Thamnophis sirtalis parietalis) at a communal den in Manitoba support an interpretation of sexual conflict rather than indirect mate choice. Female snakes dispersed rapidly from the den through areas with relatively few males rather than waiting for additional courtship. Many females dispersed without mating. Experimental (pheromonal) manipulation of the intensity of courtship accelerated rates of female dispersal rather than delaying dispersal, as would be predicted if females wait to obtain matings. The behaviors of females escaping from courting groups were maximally effective in losing their suitors regardless of the number of courting males or whether or not the female was capable of mating (recently mated females cannot mate again because of a mating plug). In total, our data are most consistent with the hypothesis that female garter snakes at communal dens evade males to escape harassment rather than to enhance mate quality.

Animals↗
PubMed2005

Salvia columbariae contains tanshinones.

Salvia columbariae (chia) was examined and found to contain miltionone II, cryptotanshinone and tanshinone IIA. These compounds may be of interest in the treatment of stroke and heart attack.

Journal Article↗
PubMed2005

The use of acetazolamide in idiopathic intracranial hypertension during pregnancy.

PURPOSE: To describe the pregnancy outcomes after the use of acetazolamide in pregnant patients with idiopathic intracranial hypertension (IIH). DESIGN: Observational case series. METHODS: setting: Two tertiary care academic neuro-ophthalmology units. patient population: Patients with IIH treated with acetazolamide. observation procedure: Documentation of pregnancy outcome. main outcome measures: Normal pregnancy, fetal loss, or congenital malformation. RESULTS: Twelve patients were treated with acetazolamide for IIH during pregnancy, and there were no adverse pregnancy outcomes. A critical review of the English language literature on the subject failed to demonstrate any convincing evidence for any adverse effect on pregnancy for acetazolamide. CONCLUSIONS: Acetazolamide at high doses may produce birth defects in animals, but there is little clinical or experimental evidence to support any adverse effect of the drug on pregnancy outcomes in humans. If the clinical situation warrants the use of acetazolamide in IIH, then the drug probably can be offered after appropriate informed consent.

Acetazolamide↗
PubMed2005

The diagnostic yield of the evaluation for isolated unexplained optic atrophy.

PURPOSE: To report the diagnostic yield for the evaluation of isolated and unexplained optic atrophy. SETTING: Two tertiary care academic neuroophthalmology clinics. DESIGN: Retrospective case series. PARTICIPANTS: Patients with optic atrophy. METHODS: Retrospective review of all charts with the diagnosis of optic atrophy. Included patients were adults with isolated, but unexplained, optic atrophy. Patients were excluded if they were children, had incomplete or inadequate documentation of the findings, had nonneurologically isolated optic atrophy (e.g., other localizing findings), or had a history (e.g., prior neuroimaging study showed a compressive lesion, prior ischemic optic neuropathy) or examination (e.g., central retinal artery occlusion) evidence for an etiology for the optic atrophy. MAIN OUTCOME MEASURE: Results of diagnostic evaluation. RESULTS: A total of 1110 charts with the diagnosis of optic atrophy were reviewed from the 2 participating institutions (368 from the University of Cincinnati and 742 from the University of Iowa). Of these 1110 charts, 91 (8%) with isolated unexplained optic atrophy were included, and 1019 charts (92%) were excluded. Of 91 included patients, 18 (20%) had a compressive lesion causing optic atrophy, and 73 (80%) cases had no etiology for the optic atrophy on neuroimaging. Of the 18 patients with abnormal imaging (e.g., meningioma, pituitary adenoma, craniopharyngioma) studies, 11 had bilateral and 7 had unilateral optic atrophy. Five of the 18 patients had progressive visual loss, 3 had hemianopic visual field loss, and 11 were younger than 50 years old. CONCLUSIONS: Patients with optic atrophy in our study typically had historical or examination findings that led to an etiologic diagnosis. Neuroimaging showed an etiology in 20% of patients. Other laboratory testing did not produce an etiologic diagnosis in the absence of a suggestive history or examination. On the basis of our results, we recommend neuroimaging for all patients with unexplained optic atrophy and consideration for directed laboratory studies only.

Brain Neoplasms↗
PubMed2005

Characteristics of the normative database for the Humphrey matrix perimeter.

PURPOSE: The Humphrey Matrix (Carl Zeiss Meditec, Dublin CA; Welch-Allyn, Skaneateles, NY) is a high-spatial-resolution perimeter that uses frequency-doubling stimuli. It incorporates an efficient test strategy that assumes that age, eccentricity, and test procedure type have only small effects on sensitivity. The results used to create the normative database for the perimeter were examined, to see whether these assumptions were met and to examine the form of the normative data. METHOD: Visual fields were measured (Matrix 30-2, 24-2, 10-2 and Macula patterns) in >275 subjects judged to be normal by a battery of clinical procedures. The right eye was always tested first. RESULTS: Sensitivity decreased by approximately 0.7 dB per age decade across all eccentricities; sensitivity decreased with eccentricity, typically by <5 dB at the most peripheral points tested. Although there was no systematic difference in sensitivity between the 30-2 and 24-2 tests, the Macula test sensitivities were typically 1 dB higher than for the 10-2 test. Sensitivity in the left eye was slightly lower than in the right, with the difference being significantly greater in the temporal visual field. In most test locations, the 95% confidence interval of normal sensitivity was approximately 6 dB below the median sensitivity. CONCLUSIONS: The performance of the test strategy in the Matrix perimeter is appropriately matched to the response characteristics of the normal population. The finding of a spatially nonuniform difference in sensitivity between left and right eyes is attributable to light-adaptation differences between the eyes. This effect is accounted for in the perimeter's normative database.

Adolescent↗
PubMed2004

Neurologic impairment 10 years after optic neuritis.

BACKGROUND: Participants enrolled in the Optic Neuritis Treatment Trial have been observed for more than a decade to assess the relationship between optic neuritis and the development of clinically definite multiple sclerosis. OBJECTIVE: To assess neurologic disability 10 to 12 years after an initial episode of optic neuritis. DESIGN: Longitudinal follow-up of a clinical trial. SETTING: Fourteen Optic Neuritis Treatment Trial clinical centers performed standardized neurologic examinations, including an assessment of neurologic disability. PARTICIPANTS: One hundred twenty-seven patients who had developed clinically definite multiple sclerosis. MAIN OUTCOME MEASURES: Functional Systems Scale and Expanded Disability Status Scale. RESULTS: The disability of most patients was mild, with 65% of patients having an Expanded Disability Status Scale score lower than 3.0. The degree of disability appeared to be unrelated to whether the baseline magnetic resonance imaging scan was lesion-free or showed lesions (P =.51). Among patients with baseline lesions, the degree of disability was unrelated to the number of lesions that were present on the scan (P =.14). Two patients died owing to severe multiple sclerosis, one of whom had no lesions revealed on the baseline scan. CONCLUSION: Most patients who develop clinically definite multiple sclerosis following an initial episode of optic neuritis will have a relatively benign course for at least 10 years.

Adult↗
PubMed2004

Presumed "sulfa allergy" in patients with intracranial hypertension treated with acetazolamide or furosemide: cross-reactivity, myth or reality?

PURPOSE: To determine whether acetazolamide or furosemide produce allergic cross-reactions in patients with self-reported "sulfa allergy." DESIGN: Retrospective case series. METHODS: A retrospective review included patients with intracranial hypertension and a self-reported sulfa allergy treated with either acetazolamide or furosemide seen at the University of Iowa Hospitals and Clinics from 1972 to 2003. All presumed medication-related side effects were collected, including both predictable adverse effects (for example, paresthesias, fatigue) and unpredictable adverse reactions (for example, cutaneous fixed eruptions, urticaria, Stevens-Johnson syndrome, toxic epidermal necrolysis, angioedema, anaphylaxis). RESULTS: We reviewed 363 charts. Of these, 329 patients (91%) were excluded. Of the remaining 34 cases that did report a so-called sulfa allergy, 13 (38%) received acetazolamide alone, 7 (21%) received furosemide alone, and 14 (41%) received both acetazolamide and furosemide. Of the 27 patients who received acetazolamide, 10 (37%) had no documented allergic cross-reaction to sulfa, and 2 (7%) cases had urticaria. The remaining 15 (56%) of acetazolamide-treated patients experienced predictable adverse reactions for this drug (for example, paresthesias). No patient experienced a severe allergic cross-reaction to sulfa. Of 21 patients who received furosemide, no unpredictable adverse reactions or allergic cross-reactions to sulfa were noted. CONCLUSIONS: We find little clinical or pharmacological evidence to suggest that a self-reported sulfa allergy is likely to produce a life-threatening cross-reaction with acetazolamide or furosemide. These medications should be considered for intracranial hypertension if the risk-to-benefit ratio warrants their use.

Acetazolamide↗
PubMed2004

Visual function more than 10 years after optic neuritis: experience of the optic neuritis treatment trial.

PURPOSE: To assess visual function more than 10 years after an episode of optic neuritis in patients enrolled in the Optic Neuritis Treatment Trial. DESIGN: Longitudinal follow-up of a randomized clinical trial. METHODS: Vision testing included measures of visual acuity, contrast sensitivity, and visual field. Quality of life was assessed with the National Eye Institute Visual Function Questionnaire. RESULTS: Examinations were completed on 319 patients. In most patients, visual function test results in the eyes that experienced optic neuritis at study entry ("affected eyes") were normal or only slightly abnormal after 9.9 to 13.7 years. Visual acuity in the affected eyes was >or=20/20 in 74%, 20/25 to 20/40 in 18%, <20/40 to 20/200 in 5%, and <20/200 in 3%. On average, visual function was worse in patients with multiple sclerosis (MS) than in those without MS. Recurrent optic neuritis in either eye occurred in 35% of patients. Such attacks were more frequent in patients with MS (P <.001). The National Eye Institute Visual Function Questionnaire scores were lower when visual acuity was abnormal and when MS was present. CONCLUSIONS: Most patients retained good to excellent vision more than 10 years after an attack of optic neuritis. Recurrences were more frequent in patients with MS.

Adolescent↗
PubMed2004

What's new in perimetry.

Despite important refinements that have improved quantitation and shortened test time, modern perimetry remains relatively insensitive and plagued by high test-retest variability. Some novel methods, though not yet fully vetted, offer the promise of improving sensitivity and reducing variability.

Evoked Potentials, Visual↗