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Biomedical subjects

P C O'Brien

Publications and source records attributed to P C O'Brien.

At least 19 recordsLinked to original sources
PubMed2007

Chromosome painting and molecular dating indicate a low rate of chromosomal evolution in golden moles (Mammalia, Chrysochloridae).

Golden moles (Chrysochloridae) are poorly known subterranean mammals endemic to Southern Africa that are part of the superordinal clade Afrotheria. Using G-banding and chromosome painting we provide a comprehensive comparison of the karyotypes of five species representing five of the nine recognized genera: Amblysomus hottentotus, Chrysochloris asiatica, Chrysospalax trevelyani, Cryptochloris zyli and Eremitalpa granti. The species are karyotypically highly conserved. In total, only four changes were detected among them. Eremitalpa granti has the most derived karyotype with 2n = 26 and differs from the remaining species (all of whom have 2n = 30) by one centric and one telomere:telomere fusion. In addition, two intrachromosomal rearrangements were detected in A. hottentotus. The painting probes also suggest the presence of a unique satellite DNA family located on chromosomes 11 and 12 of both C. asiatica and C. zyli. This represents a synapomorphy linking these two sympatric species as sister taxa. A molecular clock was calibrated adopting a relaxed Bayesian approach for multigene data sets comprising publicly available sequences derived from five gene fragments representative of three golden moles and 39 other eutherian species. The data suggest that golden moles diverged from a common ancestor approximately 28.5 mya (95% credibility interval = 21.5-36.5 mya). Based on an inferred chrysochlorid ancestral karyotype of 2n = 30, the estimated rate of 0.7 rearrangements per 10 my (95% Credibility Interval = 0.54-0.93) differs from the 'default rate' of mammalian chromosomal evolution which has been estimated at one change per 10 million years, thus placing the Chrysochloridae among the slower-evolving chromosomal lineages thus far recorded.

Animals↗
PubMed2005

Brain atrophy rates predict subsequent clinical conversion in normal elderly and amnestic MCI.

OBJECTIVE: To test the hypothesis that the atrophy rate measured from serial MRI studies is associated with time to subsequent clinical conversion to a more impaired state in both cognitively healthy elderly subjects and in subjects with amnestic mild cognitive impairment (MCI). METHODS: Ninety-one healthy elderly patients and 72 patients with amnestic MCI who met inclusion criteria were identified from the Mayo Alzheimer's Disease Research Center and Alzheimer's Disease Patient Registry. Atrophy rates of four different brain structures--hippocampus, entorhinal cortex, whole brain, and ventricle--were measured from a pair of MRI studies separated by 1 to 2 years. The time of the second scan marked the beginning of the clinical observation period. RESULTS: During follow-up, 13 healthy patients converted to MCI or Alzheimer disease (AD), whereas 39 MCI subjects converted to AD. Among those healthy at baseline, only larger ventricular annual percent volume change (APC) was associated with a higher risk of conversion (hazard ratio for a 1-SD increase 1.9, p = 0.03). Among MCI subjects, both greater ventricular volume APC (hazard ratio for a 1-SD increase 1.7, p < 0.001) and greater whole brain APC (hazard ratio for a 1-SD increase 1.4, p = 0.007) increased the risk of conversion to AD. Both ventricular APC (hazard ratio for a 1-SD increase 1.59, p = 0.001) and whole brain APC (hazard ratio for a 1-SD increase 1.32, p = 0.009) provided additional predictive information to covariate-adjusted cross-sectional hippocampal volume at baseline about the risk of converting from MCI to AD. DISCUSSION: Higher whole brain and ventricle atrophy rates 1 to 2 years before baseline are associated with an increased hazard of conversion to a more impaired state. Combining a measure of hippocampal volume at baseline with a measure of either whole brain or ventricle atrophy rates from serial MRI scans provides complimentary predictive information about the hazard of subsequent conversion from mild cognitive impairment to Alzheimer disease. However, overlap among those who did vs those who did not convert indicate that these measures are unlikely to provide absolute prognostic information for individual patients.

Age Factors↗
PubMed2005

A randomized controlled crossover trial of aspirin for fatigue in multiple sclerosis.

Pharmacotherapeutic options for multiple sclerosis (MS)-related fatigue are limited. Thirty patients were randomly assigned to aspirin (ASA) 1,300 mg/day or placebo in a double-blind crossover study. Results favored ASA for the main clinical outcomes: Modified Fatigue Impact Scale scores (p = 0.043) and treatment preference (p = 0.012). There were no significant adverse effects. The results warrant further study and support a role for ASA-influenced mechanisms, perhaps immunologic, in the generation of MS-related chronic fatigue.

Administration, Oral↗
PubMed2005

DWI predicts future progression to Alzheimer disease in amnestic mild cognitive impairment.

The authors assessed whether measures of hippocampal water diffusivity at baseline can predict future progression to Alzheimer disease (AD) in amnestic mild cognitive impairment (aMCI). Higher baseline hippocampal diffusivity was associated with a greater risk of progression to AD in aMCI (p = 0.002). Magnetic resonance diffusion-weighted imaging may help identify patients with aMCI who will progress to AD as well as or better than structural MRI measures of hippocampal atrophy.

Age Factors↗
PubMed2005

Sudden cardiac death in diabetes mellitus: risk factors in the Rochester diabetic neuropathy study.

OBJECTIVES: To determine risk factors for sudden cardiac death and the role of diabetic autonomic neuropathy (DAN) in the Rochester diabetic neuropathy study (RDNS). METHODS: Associations between diabetic and cardiovascular complications, including DAN, and the risk of sudden cardiac death were studied among 462 diabetic patients (151 type 1) enrolled in the RDNS. Medical records, death certificates, and necropsy reports were assessed for causes of sudden cardiac death. RESULTS: 21 cases of sudden cardiac death were identified over 15 years of follow up. In bivariate analysis of risk covariates, the following were significant: ECG 1 (evolving and previous myocardial infarctions): hazard ratio (HR) = 4.4 (95% confidence interval (CI), 1.6 to 12.1), p = 0.004; ECG 2 (bundle branch block or pacing): HR = 8.6 (2.9 to 25.4), p<0.001; ECG 1 or ECG 2: HR = 4.2 (1.3 to 13.4), p = 0.014; and nephropathy stage: HR = 2.1 (1.3 to 3.4), p = 0.002. Adjusting for ECG 1 or ECG 2, autonomic scores, QTc interval, high density lipoprotein (HDL) cholesterol, 24 hour microalbuminuria, and 24 hour total proteinuria were significant. However, adjusting for nephropathy, none of the autonomic indices, QTc interval, HDL cholesterol, microalbuminuria, or total proteinuria was significant. At necropsy, all patients with sudden cardiac death had coronary artery or myocardial disease. CONCLUSIONS: Sudden cardiac death was correlated with atherosclerotic heart disease and nephropathy, and to a lesser degree with DAN and HDL cholesterol. Although DAN is associated with sudden cardiac death, it is unlikely to be its primary cause.

Aged↗
PubMed2004

Injuries due to seizures in persons with epilepsy: a population-based study.

BACKGROUND: Previous studies of injuries due to epileptic seizures predominantly involved patients with intractable epilepsy. These studies may have overestimated the risk of injuries in persons with epilepsy. METHODS: Patients consisted of 247 Rochester, MN, residents who were diagnosed with epilepsy between 1975 and 1984. Seizure-related injuries were defined as any injury, other than orolingual trauma, resulting from a seizure, sufficient for the patient to seek medical attention or for injury occurrence to be determined during the course of medical care. To identify risk factors for injury, characteristics of patients with seizure-related injury were compared with those without injury. RESULTS: During a total of 2,714 patient-years of follow-up, 62 seizure-related injuries were identified in 39 patients (16%, one injury in every 44 person-years). Most injuries involved cranial soft tissue contusions or lacerations (79%). The majority of seizure-related injuries (82%) occurred during generalized convulsive seizures. Univariate analyses identified five potential risk factors for seizure-related injury: greater number of antiepileptic drugs used, less independent living situation, higher Rankin score, history of generalized convulsive seizures or drop attacks, and higher seizure frequency score. Seizure frequency, however, was the only significant risk factor identified by multivariate analysis (p < 0.001; relative risk, 1.33). CONCLUSIONS: This population-based study shows that seizure-related injuries are infrequent and generally of minor severity. In most epilepsy patients, excessive restriction of daily activities to avoid injury is unnecessary. Effective seizure control reliably reduces the risk of seizure-related injuries.

Adolescent↗
PubMed2004

1H MR spectroscopy in common dementias.

OBJECTIVE: To determine the 1H MR spectroscopic (MRS) findings and intergroup differences among common dementias: Alzheimer disease (AD), vascular dementia (VaD), dementia with Lewy bodies (DLB), and frontotemporal lobar degeneration (FTLD). METHODS: The authors consecutively recruited 206 normal elderly subjects and 121 patients with AD, 41 with FTLD, 20 with DLB, and 8 with VaD. The 1H MRS metabolite ratio changes in common dementias were evaluated with respect to normal and also differences among the common dementias. RESULTS: N-acetylaspartate (NAA)/creatine (Cr) was lower than normal in patients with AD, FTLD, and VaD. Myo-inositol (mI)/Cr was higher than normal in patients with AD and FTLD. Choline (Cho)/Cr was higher than normal in patients with AD, FTLD, and DLB. There were no metabolite differences between patients with AD and FTLD or between patients with DLB and VaD. NAA/Cr was lower in patients with AD and FTLD than DLB. MI/Cr was higher in patients with AD and FTLD than VaD. MI/Cr was also higher in patients with FTLD than DLB. CONCLUSIONS: NAA/Cr levels are decreased in dementias that are characterized by neuron loss, such as AD, FTLD, and VaD. MI/Cr levels are elevated in dementias that are pathologically characterized by gliosis, such as AD and FTLD. Cho/Cr levels are elevated in dementias that are characterized by a profound cholinergic deficit, such as AD and DLB.

Acetylcholine↗
PubMed2004

Comparison of different MRI brain atrophy rate measures with clinical disease progression in AD.

OBJECTIVE: To correlate different methods of measuring rates of brain atrophy from serial MRI with corresponding clinical change in normal elderly subjects, patients with mild cognitive impairment (MCI), and patients with probable Alzheimer disease (AD). METHODS: One hundred sixty subjects were recruited from the Mayo Clinic Alzheimer's Disease Research Center and Alzheimer's Disease Patient Registry Studies. At baseline, 55 subjects were cognitively normal, 41 met criteria for MCI, and 64 met criteria for AD. Each subject underwent an MRI examination of the brain at the time of the baseline clinical assessment and then again at the time of a follow-up clinical assessment, 1 to 5 years later. The annualized changes in volume of four structures were measured from the serial MRI studies: hippocampus, entorhinal cortex, whole brain, and ventricle. Rates of change on several cognitive tests/rating scales were also assessed. Subjects who were classified as normal or MCI at baseline could either remain stable or convert to a lower-functioning group. AD subjects were dichotomized into slow vs fast progressors. RESULTS: All four atrophy rates were greater among normal subjects who converted to MCI or AD than among those who remained stable, greater among MCI subjects who converted to AD than among those who remained stable, and greater among fast than slow AD progressors. In general, atrophy on MRI was detected more consistently than decline on specific cognitive tests/rating scales. With one exception, no differences were found among the four MRI rate measures in the strength of the correlation with clinical deterioration at different stages of the disease. CONCLUSIONS: These data support the use of rates of change from serial MRI studies in addition to standard clinical/psychometric measures as surrogate markers of disease progression in AD. Estimated sample sizes required to power a therapeutic trial in MCI were an order of magnitude less for MRI than for change measures based on cognitive tests/rating scales.

Aged↗
PubMed2003

Comparison of memory fMRI response among normal, MCI, and Alzheimer's patients.

OBJECTIVE: To determine whether an fMRI memory encoding task distinguishes among cognitively normal elderly individuals, patients with mild cognitive impairment (MCI), and patients with early Alzheimer's disease (AD). METHODS: Twenty-nine subjects (11 normal, 9 MCI, 9 AD) were studied with an fMRI memory encoding task. A passive sensory task was also performed to assess potential intergroup differences in fMRI responsiveness. Activation in the medial temporal lobe for the memory task and in the anatomic rolandic area for the sensory task was studied. Intergroup comparisons were performed using receiver operating characteristic (ROC) analyses. The ROC method provides rigorous control of artifactual false-positive "activation." Subjects were tested for recall and recognition of the encoding task stimuli following the fMRI study. RESULTS: Medial temporal lobe activation was greater in normal subjects than MCI and AD patients (p = 0.03 and p = 0.04). There was no difference between AD and MCI patients in fMRI memory performance [corrected]. There was an association between fMRI memory activation (area under the ROC curve) and post-fMRI performance on recognition and free recall. There was no difference among the three groups on the sensory task. CONCLUSIONS: MCI and AD patients had less medial temporal lobe activation on the memory task than the normal subjects but similar activation as normal subjects on the sensory task. These findings suggest decreased medial temporal activation may be a specific marker of limbic dysfunction due to the neurodegenerative changes of AD. In addition, fMRI is sufficiently sensitive to detect changes in the prodromal, MCI, phase of the disease.

Aged↗
PubMed2003

MRI as a biomarker of disease progression in a therapeutic trial of milameline for AD.

OBJECTIVE: To assess the feasibility of using MRI measurements as a surrogate endpoint for disease progression in a therapeutic trial for AD. METHODS: A total of 362 patients with probable AD from 38 different centers participated in the MRI portion of a 52-week randomized placebo-controlled trial of milameline, a muscarinic receptor agonist. The therapeutic trial itself was not completed due to projected lack of efficacy on interim analysis; however, the MRI arm of the study was continued. Of the 362 subjects who underwent a baseline MRI study, 192 subjects underwent a second MRI 1 year later. Hippocampal volume and temporal horn volume were measured from the MRI scans. RESULTS: The annualized percent changes in hippocampal volume (-4.9%) and temporal horn volume (16.1%) in the study patients were consistent with data from prior single-site studies. Correlations between the rate of MRI volumetric change and change in behavioral/cognitive measures were greater for the temporal horn than for the hippocampus. Decline over time was more consistently seen with imaging measures, 99% of the time for the hippocampus, than behavioral/cognitive measures (p < 0.001). Greater consistency in MRI than behavioral/clinical measures resulted in markedly lower estimated sample size requirements for clinical trials. The estimated number of subjects per arm required to detect a 50% reduction in the rate of decline over 1 year are: AD Assessment Scale-cognitive subscale 320; Mini-Mental Status Examination 241; hippocampal volume 21; temporal horn volume 54. CONCLUSION: The consistency of MRI measurements obtained across sites, and the consistency between the multisite milameline data and that obtained in prior single-site studies, demonstrate the technical feasibility of using structural MRI measures as a surrogate endpoint of disease progression in therapeutic trials. However, validation of imaging as a biomarker of therapeutic efficacy in AD awaits a positive trial.

Adolescent↗
PubMed2002

Antemortem MRI findings correlate with hippocampal neuropathology in typical aging and dementia.

OBJECTIVES: To assess the diagnostic specificity of MRI-defined hippocampal atrophy for AD among individuals with a variety of pathologically confirmed conditions associated with dementia as well as changes attributable to typical aging, and to measure correlations among premortem MRI measurements of hippocampal atrophy, mental status examination performance, and the pathologic stage of AD. METHODS: An unselected series of 67 individuals participating in the Mayo Alzheimer's Disease Research Center/Alzheimer's Disease Patient Registry who had undergone a standardized antemortem MRI study and also postmortem examination were identified. Hippocampal volumes were measured from antemortem MRI. Each postmortem specimen was assigned a pathologic diagnosis and in addition, the severity of AD pathology was staged using the method of Braak and Braak. RESULTS: Individuals with an isolated pathologic diagnosis of AD, hippocampal sclerosis, frontotemporal degeneration, and neurofibrillary tangle--only degeneration usually had substantial hippocampal atrophy, while those with changes of typical aging did not. Among all 67 subjects, correlations (all p < 0.001) were observed between hippocampal volume and Braak and Braak stage (r = -0.39), between hippocampal volume and Mini-Mental State Examination (MMSE) score (r = 0.60), and between MMSE score and Braak and Braak stage (r = -0.41). CONCLUSIONS: Hippocampal atrophy, while not specific for AD, was a fairly sensitive marker of the pathologic AD stage (particularly among subjects with isolated AD pathology [r = -0.63, p = 0.001]) and consequent cognitive status.

Aged↗
PubMed2002

Cytogenetic analysis of California condor (Gymnogyps californianus) chromosomes: comparison with chicken (Gallus gallus) macrochromosomes.

The California condor is the largest flying bird in North America and belongs to a group of New World vultures. Recovering from a near fatal population decline, and currently with only 197 extant individuals, the species remains listed as endangered. Very little genetic information exists for this species, although sexing methods employing chromosome analysis or W-chromosome specific amplification is routinely applied for the management of this monomorphic species. Keeping in mind that genetic conditions like chondrodystrophy have been identified, preliminary steps were undertaken in this study to understand the genome organization of the condor. This included an extensive cytogenetic analysis that provided (i) a chromosome number of 80 (with a likelihood of an extra pair of microchromosomes), and (ii) information on the centromeres, telomeres and nucleolus organizer regions. Further, a comparison between condor and chicken macrochromosomes was obtained by using individual chicken chromosome specific paints 1-9 and Z and W on condor metaphase spreads. Except for chromosomes 4 and Z, each of the chicken (GGA) macrochromosomes painted a single condor (GCA) macrochromosome. GGA4 paint detected complete homology with two condor chromosomes, viz., GCA4 and GCA9 providing additional proof that the latter are ancestral chromosomes in the birds. The chicken Z chromosome showed correspondence with both Z and W in the condor. The homology suggests that the condor sex chromosomes have not completely differentiated during evolution, which is unlike the majority of the non-ratites studied up till now. Overall, the study provides detailed cytogenetic and basic comparative information on condor chromosomes. These findings significantly advance the effort to study the chondrodystrophy that is responsible for over ten percent mortality in the condor.

Animals↗
PubMed2001

Feasibility of an affected sibling pair study in ischemic stroke: results of a 2-center family history registry.

BACKGROUND AND PURPOSE: We sought to determine pedigree availability for a concordant sibling pair study of genetic risk factors in ischemic stroke. METHODS: Probands with confirmed ischemic stroke were prospectively enrolled. Family histories were obtained by systematic interview. A study neurologist prospectively assigned stroke subtype. RESULTS: Of 310 probands (median age, 75 years; range, 26 to 97 years; 48% women), 75% had at least 1 living sibling; 10%, at least 1 concordant living sibling; 2%, at least 1 concordant sibling living in the same city; and 7%, at least 1 concordant living and 1 discordant living sibling. Likelihood of having a concordant sibling increased significantly with proband age, even after adjustment for sibship size (P=0.002). Positive family history of stroke was not related to either proband stroke subtype or risk factor profile. CONCLUSIONS: Approximately 10 probands were screened to find 1 potentially concordant living sibling. A concordant sibling pair study should be multicentered and enable enrollment of siblings from diverse geographic areas.

Adult↗
PubMed2001

Increased weakness after pancreas and kidney transplantation.

BACKGROUND: Already there is evidence that simultaneous pancreas and kidney (SPK), or pancreas after kidney (PAK) transplantation, in patients with type 1 diabetes mellitus and end-stage kidney disease prevents worsening of diabetic polyneuropathy, but neuropathic improvement is delayed and incomplete. METHODS: In 85 patients with type 1 diabetes mellitus who underwent SPK or PAK transplantations, we performed sequential neuromuscular evaluations before, every 3 months after, and yearly after transplantation, quantitating muscle weakness separately from overall severity of polyneuropathy. RESULTS: We found that, on average, the weakness subscore of the Neuropathy Impairment Score of the lower limbs [NIS(LL)-W] was significantly worse at 3, 6, 9, and 12 months (by about 5 points) than at baseline. By contrast, for these times after transplantation, a composite score of nerve conduction abnormalities, an independent measure of severity of polyneuropathy, was not significantly worse and, in fact, was significantly improved. In multivariate analysis, length of hospital stay correlated with the increased weakness. CONCLUSIONS: We conclude that: (1) increased neuromuscular impairment after transplantation is mainly due to muscle weakness and not to worsening polyneuropathy; (2) in multivariate analysis, duration of hospitalization after transplantation was significantly associated with this increased weakness; (3) increased weakness is probably due to development of myopathy, which may be related to graft rejection, immunosuppression, sepsis, and intercurrent infections; (4) in future transplantation trials, weakness should be evaluated separately from neuropathic status, and the lowest efficacious dosages of immunotherapy should be used; and (5) essentially all diabetic patients reported that SPK or PAK transplantation was worthwhile because it freed them from diabetic lifestyle concerns.

Adolescent↗
PubMed2001

Prospective analysis of risk factors for nursing home placement of dementia patients.

OBJECTIVE: To examine risk factors for nursing home placement in a community-based dementia cohort. METHODS: Cognitively normal participants and cognitively impaired patients from a large AD Patient Registry were followed from diagnosis to placement, death, or last follow-up. This included over 3,600 person-years of surveillance. The normal group included 473 participants who did not, at any point, meet Diagnostic and Statistical Manual of Mental Disorders, 3rd ed., revised (DSM-III-R) criteria for dementia. The patient group included 512 patients who met DSM-III-R criteria for dementia or criteria for mild cognitive impairment at diagnosis. Demographic, medical, social, cognitive, behavioral, and functional predictors of time to placement were examined using Cox modeling. RESULTS: In the normal group, only 21 people (4%) required nursing home placement. With subjects, enrollment year, age at initial evaluation, being widowed, and living in a retirement community were associated with time to placement in separate univariate analyses. Of 512 cognitively impaired patients, 203 (39.6%) were placed in nursing homes. Median time from diagnosis to placement was 5.3 years. Within the patient sample, four predictors were determined to be associated with time to nursing home placement. These included gender, enrollment year, functional status, and cognitive score. Interactions were present for functional status with cognitive score and enrollment year. CONCLUSION: In patients with dementia who are within 5 years of diagnosis, placement rates of approximately 10% per year can be expected. Disease severity indices including degree of cognitive and functional impairment are primary risk factors for placement.

Activities of Daily Living↗
PubMed2001

Diagnostic accuracy and certainty from sequential evaluations in peripheral neuropathy.

Three masked neuromuscular experts analyzed the contribution of the data from sequential evaluations in predicting specific varieties of peripheral neuropathy in 72 patients. The largest improvement (16%) in diagnostic accuracy resulted from presentation of neurologic history. By contrast, diagnostic confidence increased gradually with presentation of additional medical information. Therefore, the authors conclude that for diagnostic accuracy and certainty, expert neuromuscular judgment and extensive characterizing or discriminative testing are needed.

Cohort Studies↗