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Biomedical subjects

D M Wingerchuk

Publications and source records attributed to D M Wingerchuk.

17 recordsLinked to original sources
PubMed2002

Is there a neurologist on this flight?

OBJECTIVE: To analyze the frequency of neurologic events during commercial airline flights and to assess whether onboard emergency medical kits are adequate for in-flight neurologic emergencies. METHODS: Collaboration of the Mayo Clinic's Departments of Emergency Medicine and Medical Transportation Service and the Division of Aerospace Medicine to provide real-time in-flight consultation to a major US airline that flies approximately 10% of all US passengers. We analyzed all medical events reported from 1995 to 2000 in a database that catalogs the air-to-ground medical consultations. All cases with potential neurologic symptoms were reviewed and classified into various neurologic symptom categories. The cost of diversion for each neurologic symptom was calculated and then extrapolated to assess the cost of neurologic symptoms to the US airline industry. RESULTS: A total of 2,042 medical incidents led to 312 diversions. Neurologic symptoms were the single largest category of medical incidents, prompting 626 air-to-ground medical calls (31%). They caused 34% of all diversions. Dizziness/vertigo was the most common neurologic symptom followed by seizures, headaches, pain, and cerebrovascular symptoms. Whereas seizures and dizziness/vertigo were the most common reasons for diversion, loss of consciousness/syncope was the complaint most likely to lead to a diversion. The estimated annual cost of diversions due to neurologic events is almost 9,000,000 dollars. CONCLUSION: Neurologic symptoms are the most common medical complaint requiring air-to-ground medical support and are second only to cardiovascular problems for emergency diversions and their resultant costs to the US airline industry. Adding antiepileptic drugs to the onboard medical kit and greater emergency medical training for in-flight personnel could potentially reduce the number of diversions for in-flight neurologic incidents.

Aircraft↗
PubMed2001

A randomized trial of intravenous immunoglobulin in inflammatory demyelinating optic neuritis.

OBJECTIVE: To determine whether IV immunoglobulin (IVIg) reverses chronic visual impairment in MS patients with optic neuritis (ON). METHODS: In this double-blind, placebo-controlled Phase II trial, 55 patients with persistent acuity loss after ON were randomized to receive either IVIg 0.4 g/kg daily for 5 days followed by three single infusions monthly for 3 months, or placebo. RESULTS: The trial was terminated by the National Eye Institute because of negative results when 55 of the planned 60 patients had been enrolled. Fifty-two patients completed the scheduled infusions, and 53 patients completed 12 months of follow-up. Analysis of this data indicated that a difference between treatment groups was not observed for the primary outcome measure, improvement in logMAR visual scores at 6 months (p = 0.766). Exploratory secondary analyses suggested that IVIg treatment was associated with improvement in visual function (including logMAR visual scores at 6 months and visual fields at 6 and 12 months) in patients with clinically stable MS during the trial. CONCLUSIONS: IVIg administration does not reverse persistent visual loss from ON to a degree that merits general use.

Adult↗
PubMed2001

Early versus late antiepileptic drug withdrawal for people with epilepsy in remission.

BACKGROUND: Antiepileptic drugs ( AEDs) are used to prevent seizures but are associated with both short and long term adverse effects. When epilepsy is in remission, it may be in the patient's best interest to discontinue medication. However, the optimal timing of AED discontinuation is not known. OBJECTIVES: To quantify seizure relapse risk after early (less than two seizure free years) versus late (more than two seizure free years) AED withdrawal in adult and pediatric epilepsy patients. To assess which variables modify the risk of seizure recurrence. SEARCH STRATEGY: We searched the Cochrane Epilepsy Group trials register, the Cochrane Controlled trials register (Cochrane Library Issue 4, 2000), MEDLINE (January 1996 to January 2001), EMBASE, Index Medicus, CINAHL, as well as hand-searching of journals. SELECTION CRITERIA: Randomized controlled trials that evaluate withdrawal of AEDs after varying periods of seizure remission in adult and pediatric epilepsy patients with or without blinding were included. Included studies compared an early versus late AED discontinuation. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data and assessed trial quality. Relative risks with 95% confidence intervals were calculated for each trial. Summary relative risks and 95% confidence intervals for dichotomous data were calculated using a random effects model. A test of statistical heterogeneity was conducted for each pooled relative risk calculation. MAIN RESULTS: Seven eligible controlled trials were included in the analysis representing 924 randomized pediatric patients. There were no eligible trials evaluating adult seizure free patients. The pooled relative risk for seizure relapse in early versus late AED withdrawal was 1.32 (95% confidence interval 1.02 to 1.70). On the basis of this estimate, the number needed to harm, that is expose an individual to a higher risk of seizure relapse because of early withdrawal of AED, is 10. Early discontinuation was associated with greater relapse rates in patients with partial seizures[pooled RR = 1.52; 95% confidence interval 0.95 to 2.41] or an abnormal EEG [pooled RR=1.67; 95% confidence interval 0.93 to 3.00]. REVIEWER'S CONCLUSIONS: There is evidence to support waiting for at least two or more seizure free years before discontinuing AEDs in children, particularly if individuals have an abnormal EEG and partial seizures. There is insufficient evidence to establish when to withdraw AEDs in pediatric patients with generalized seizures. There is no evidence to guide the timing of withdrawal of AEDs in adult seizure free patients. Further blinded randomized controlled trials are needed to identify the optimal timing of AED withdrawal and risk factors predictive of relapse.

Adult↗
PubMed2001

Multiple sclerosis: current pathophysiological concepts.

Multiple sclerosis (MS) is an often disabling disease primarily affecting young adults that exhibits extraordinary clinical, radiological, and pathological heterogeneity. We review the following: (a) known environmental and genetic factors that contribute to MS susceptibility; (b) current knowledge regarding fundamental pathophysiological processes in MS, including immune cell recruitment and entry into the central nervous system (CNS), formation of the plaque, and orchestration of the immune response; (c) descriptive and qualitative distinct pathological patterns in MS and their implications; (d) the evidence supporting the causative role of direct toxins, cell-mediated and humorally mediated immune mechanisms, and the concept of a "primary oligodendrogliopathy" in demyelination and axonal injury; (e) the potential benefits of inflammation; (f) the prospects for remyelination; and (g) therapeutic implications and approaches suggested by putative pathophysiological mechanisms.

Humans↗
PubMed2000

The natural history of multiple sclerosis: a geographically based study: 8: familial multiple sclerosis.

We have examined the demographics and long-term outcome of 1044 patients with sporadic and familial multiple sclerosis in a population-based cohort from London, Ontario. The mean follow-up was 25 years in duration, and by this time most patients had reached the unambiguous endpoint scores of the Kurtzke disability status scale (DSS), DSS 6, 8 or 10. An affected family member was identified in 19.8% of the total population, and this subgroup was further divided arbitrarily into the following three groups by the type and number of relatives affected: (i) first degree only; (ii) first degree plus others; (iii) second or third degree. The outcome in these groups was compared with that for those patients who, at a mean 25 year follow-up, had no relatives known to be affected. Familial cases closely resembled those remaining sporadic in both demographics and outcome, although onset in the most heavily loaded families was earlier and male/female ratio was greater. The times to DSS 6, 8 and 10 did not differ significantly when sporadic, familial and familial subgroups were compared. These results provide no clinical support for viewing familial multiple sclerosis as distinct from the sporadic form. The observed recurrence rate for siblings in a strictly defined epidemiological sample was 3.5%, much as projected. These results validate the recurrence risks which have previously been derived from age-corrected data for these first-degree relatives.

Adult↗
PubMed2000

Multiple sclerosis: epidemiology, genetics, classification, natural history, and clinical outcome measures.

Advances in MR imaging and randomized controlled-trial methodology have fundamentally altered the diagnosis and investigation of multiple sclerosis (MS). Further progress in epidemiology and classification will provide clues toward identification of the genetic and environmental factors that predispose to MS and dictate its course. More detailed understanding of the descriptive natural (untreated) history of the disease and development of intermediate and surrogate outcome measures, with better validity and reliability, will increase the likelihood that future clinical trials will identify beneficial treatments to reduce disability. This article reviews the current state of knowledge of MS epidemiology, genetics, disease classification, natural history, and outcome measures.

Cross-Sectional Studies↗
PubMed1999

The clinical course of neuromyelitis optica (Devic's syndrome).

OBJECTIVES: To evaluate the spectrum of neuromyelitis optica (NMO), including characteristics of the index events (optic neuritis [ON]) and myelitis), neuroimaging, CSF, and serologic studies, and to evaluate the long-term course. METHODS: Review of 71 patients with NMO evaluated at the Mayo Clinic between 1950 and 1997. RESULTS: NMO was either monophasic or relapsing. Patients with a monophasic course (n = 23) usually presented with rapidly sequential index events (median 5 days) with moderate recovery. Most with a relapsing course (n = 48) had an extended interval between index events (median 166 days) followed within 3 years by clusters of severe relapses isolated to the optic nerves and spinal cord. Most relapsing patients developed severe disability in a stepwise manner, and one-third died because of respiratory failure. Features of NMO distinct from "typical" MS included >50 cells/mm3 in CSF (often polymorphonuclear), normal initial brain MRI, and lesions extending over three or more vertebral segments on spinal cord MRI. CONCLUSIONS: Clinical, laboratory, and imaging features generally distinguish neuromyelitis optica from MS. Patients with relapsing optic neuritis and myelitis may have neuromyelitis optica rather than MS. Patients with a relapsing course of neuromyelitis optica have a poor prognosis and frequently develop respiratory failure during attacks of cervical myelitis.

Adolescent↗
PubMed1999

Genetic variants in the tumor necrosis factor receptor 1 gene in patients with MS.

We scanned for all genetic variants in functionally important regions of the tumor necrosis factor receptor 1 gene (TNF-R1) in 100 to 111 MS patients from Olmsted County, MN, and analyzed selected variants for an association with disease course and severity. Ten genetic variants were uncovered. Only one variant, a silent substitution, was found in coding sequence. One intronic variant may generate a novel splice-junction sequence. We did not find an association between either this intronic variant or another common promoter variant and the course or severity of MS.

Chromosome Mapping↗
PubMed1999

The natural history of multiple sclerosis: implications for trial design.

The understanding of the natural history of multiple sclerosis has many implications for the design and interpretation of randomized controlled trials. Selection criteria, patient stratification, outcome measurements, and definitions of treatment failure can influence randomized controlled trial results and limit comparisons among trials. The focus of future studies should shift from short-term determinations of efficacy to definitive evaluations of long-term effectiveness. This will require novel investigative strategies such as the use of historic controls derived from natural history studies.

Disease Progression↗
PubMed1998

Paraneoplastic encephalomyelitis and seminoma: importance of testicular ultrasonography.

We report two patients with paraneoplastic limbic and brainstem encephalitis associated with occult nonmetastatic testicular seminoma. In each patient, the neoplasm was detectable only by testicular ultrasonography. Male patients with this syndrome in whom lung cancer is not found should undergo testicular ultrasonography as part of the search for an extrapulmonary neoplasm. A normal clinical testicular examination is insufficient to exclude an occult seminoma.

Adult↗
PubMed1998

Denaturation fingerprinting: two related mutation detection methods especially advantageous for high G + C regions.

Two versions of denaturation fingerprinting (dnF2R and dnF1R are described for detecting mutations. DnF2R is a sensitive screening method in which fingerprints are generated by performing denaturing gel electrophoresis on bidirectional "cycle-sequencing" reactions with each of two dideoxy terminators, e.g. ddATP and ddCTP. When the fingerprints generated by ddATP and ddCTP are combined, all sequence changes are expected to result in one extra and one absent segment. DnF2R was performed on 246- and 318-bp segments of the human factor IX gene, and the products were electrophoresed through a 6% Long Ranger gel with 7 M urea. All 32 single-base mutations were detected in hemizygous males with hemophilia B. DnF2R has been applied to detect a total of seven heterozygous sequence changes in large-scale screening and was found to be especially suitable for high G+C regions. In a blinded analysis, all of twenty-four additional single-base mutations were detected, but 7 of 31 heterozygous mutations were missed (23%). To reduce the effort of dnF2R by almost twofold while retaining the ability to detect all types of single-base changes, one fingerprint (dnF1R) was generated by performing a single reaction with ddATP and a second chemically modified terminator (e.g., ROX-conjugated ddCTP), which retards the mobility of the same termination products. The sensitivity and specificity of dnF1R equaled that of dnF2R, with the exception that the blinded analysis of heterozygotes in the 318-bp segment, which revealed the presence of an additional mutation. DnF under partially denaturing conditions may have optimal sensitivity for the detection of heterozygotes.

DNA Fingerprinting↗
PubMed1997

Genetic variation in the tumor necrosis factor alpha gene and the outcome of multiple sclerosis.

The objective of this study was to determine whether sequence variation in the tumor necrosis factor alpha (TNF alpha) gene is associated with MS course and severity in Olmsted County, MN. The severity and temporal course of MS are heterogeneous. Genetic factors may play a role in determining the course of MS. TNF alpha expression is temporally associated with exacerbations of MS and is increased in individuals with progressive disease. The entire TNF alpha gene was amplified by polymerase chain reaction in 78 MS patients and in 39 patients with schizophrenia. Denaturation finger-printing, a modification of direct sequencing that detects virtually all genetic polymorphisms, was performed for four regions spanning the functionally significant portions of the gene, including the promoter region. Polymorphisms were confirmed by complete sequencing. The severity and temporal course of MS were compared in those with wild-type versus variant alleles. Four sequence changes were detected, three of which occurred in MS patients. None occurred in a protein-encoding sequence. Neither of the two most common sequence variants were associated with disease severity or temporal course. Genetic variation of the TNF alpha gene is not associated with variation in the course or long-term outcome of MS in this population-based sample.

Alleles↗
PubMed1997

Multifocal brain MRI artifacts secondary to embolic metal fragments.

We report a patient with unusual MRI abnormalities that had the physical characteristics of ferromagnetic artifact. We believe that the MRI artifacts were due to microscopic embolic metal fragments, most likely from a mechanical heart valve prosthesis. Potential sources of metal emboli should be considered in patients with MRI abnormalities compatible with ferromagnetic artifact.

Adult↗
PubMed1997

Clinical outcome measures and rating scales in multiple sclerosis trials.

In this review, we analyzed clinical outcome measures used in multiple sclerosis (MS) clinical trials in which the primary goal is to slow or arrest progression of disease. In addition, we examined rating scales that quantify symptomatic complications of MS (for example, spasticity) and the current role of magnetic resonance imaging in MS treatment trials. Each proposed scale has advantages and deficiencies, and none meets all the criteria for an ideal outcome measure. The validity of trial design may be improved by using combinations of selected components of current scales as well as new instruments targeted to specific variables (such as motor strength). Symptom-specific rating scales are most appropriately used in trials of symptomatic therapeutic strategies for MS. Until serial magnetic resonance imaging changes are definitely known to predict long-term impairment and disability in patients with MS, clinical outcome measures will remain the primary means of assessing therapeutic efficacy in phase III clinical trials.

Clinical Trials, Phase III as Topic↗
PubMed1994

The effects of monoamine oxidase B inhibition on dopamine metabolism in rats with nigro-striatal lesions.

The purpose of this study was to examine whether monoamine oxidase type B (MAO-B) has a role in striatal dopamine metabolism in animals with a unilateral lesion of the medial forebrain bundle, and whether 2-phenylethylamine (PE) could have a role in amplification of dopamine (DA) responses in DA depleted striatum. Inhibition of MAO-B did not alter DA metabolism in lesioned striata. PE accumulation decreased with loss of DA as long as there was no DA dysfunction. In lesioned striata with dysfunction of DA transmission at the synaptic level, PE accumulation increased, suggesting a compensatory increase in PE synthesis. This increase in PE levels does not appear to be mediated by an increase in the total striatal aromatic L-amino acid decarboxylase (AADC) activity. We conclude that inhibition of MAO-B has no effect on DA metabolism in the hemi-parkinsonian rat striatum and that PE could be involved in the antiparkinsonian action of MAO-B inhibitors.

Animals↗
PubMedDate not supplied

Cerebral venous thrombosis complicated by hemorrhagic infarction: factors affecting the initiation and safety of anticoagulation.

BACKGROUND AND PURPOSE: Anticoagulation (AC) may improve outcome in cerebral venous thrombosis (CVT), even when complicated by pretreatment hemorrhagic infarction (HI). The HI characteristics which affect the decision to initiate AC therapy and its outcome are unknown. We reviewed our experience with AC treatment for patients with CVT and HI. METHODS: Retrospective study. RESULTS: Two groups of patients were compared: those who received AC (n = 6) and those who did not (n = 6). Hemorrhage volumes ranged from petechial to large (93 cm3) hematoma with mass effect. Anticoagulated patients received treatment a mean of 11.3 days after symptom onset. Each had exclusively extratemporal HI without midline shift and had stable hemorrhage volumes and clinical status for at least 24 h prior to AC. AC did not increase HI volume or worsen clinical outcome. All 6 non-AC patients had enlarging hematomas. Four of these 6 patients had temporal HI; and two required hematoma resection. CONCLUSIONS: AC therapy was avoided in CVT patients with HI that were located in the temporal lobe, caused midline shift or were enlarging. AC was safely initiated within several days in clinically stable patients with non-temporal-lobe HI of unchanging volume. We suggest that the location and unchanged volume on serial CT may be important factors influencing the safety of AC therapy in patients with CVT and HI.

Adolescent↗