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Biomedical subjects

P C O'Brien

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

At least 109 records · Page 6Linked to original sources

Health care utilization in multiple sclerosis: a population-based study in Olmsted County, MN.

OBJECTIVE: The authors sought to determine acute ambulatory- and hospital-billed charges for the Olmsted County, Minnesota Multiple Sclerosis (MS) Disability Prevalence Cohort and compare them to those incurred by the general population. METHODS: Billed charges for 155 people with clinically definite or laboratory-supported MS were compared with those of age- and gender-matched non-MS controls. Billing data, including all inpatient and outpatient acute and rehabilitative medical care charges over a 5-year period surrounding a December 1, 1991 prevalence date, were analyzed. Data were correlated with level of disability using the Minimal Record of Disability for MS. RESULTS: Median total annual billed charges for most individuals with MS, including those with less severe ($1,277) and relapsing-remitting illness ($1,348), did not differ from those for controls ($1,327, p=0.075). Only those with severe MS (22.6%) had median annual medical charges higher than controls ($5,440, p < 0.001). Male patients with MS had higher median annual total charges ($2,353) than male controls ($762, p=0.003). Total charges for female patients with MS ($1,440) were not different from those for female controls ($1469). Median annual outpatient charges were 15% more for the MS group ($1,418) than for controls ($1,231). Patients with MS had a mean of 0.2 hospital admissions annually compared with 0.1 annual admissions per control patient. Among variables collected on persons with MS, the Expanded Disability Status Scale was the strongest predictor of level of charges (p < 0.001). CONCLUSION: Acute ambulatory- and hospital-billed charges for most patients with MS do not differ from those of the general population.

Cohort Studies↗

Predictors of outcome of anterior temporal lobectomy for intractable epilepsy: a multivariate study.

OBJECTIVE: To identify presurgical and postsurgical factors that are independently predictive of the outcome of anterior temporal lobectomy (ATL) for intractable epilepsy. BACKGROUND: There have been reports of prognostic factors in epilepsy surgery, but little is known about factors that independently predict outcome of ATL. METHODS: We studied 175 consecutive ATL patients who had at least 2 years of postsurgical follow-up. Significant factors on univariate analyses were subjected to stepwise logistic regression analysis. RESULTS: On univariate analyses, two presurgical conditions were significantly associated with excellent seizure control at last follow-up: (1) unilateral hippocampal formation atrophy as detected on MRI and (2) all scalp interictal epileptiform discharges concordant with the location of ictal onset (p < 0.05). Three postsurgical factors that occurred during the first year were associated with excellent seizure outcome: the absence of interictal epileptiform discharges at 3 months, complete seizure control, and having only nondisabling seizures for those who did not become seizure free. Logistic regression analysis revealed the following to be independently predictive of excellent seizure control: MRI-detected unilateral hippocampal formation atrophy, concordant interictal epileptiform discharges, complete seizure control during the first postsurgical year, and having only nondisabling seizures during the first postsurgical year for those who did not become seizure free. CONCLUSIONS: Presurgical identification of unilateral hippocampal formation atrophy, or of interictal epileptiform discharges that are all concordant with the location of ictal onset, predict excellent outcome of ATL. However, the probability of excellent outcome is highest (94%) when both factors are present.

Adolescent↗

Rate of medial temporal lobe atrophy in typical aging and Alzheimer's disease.

OBJECTIVES: To determine the annual rates of volumetric change of the hippocampus and temporal horn in cognitively normal elderly control subjects and individually matched patients with AD, and to test the hypothesis that these rates were different. BACKGROUND: Cross-sectional studies consistently reveal cerebral atrophy in elderly nondemented subjects compared with healthy young adults, and greater atrophy in patients with AD relative to elderly control subjects. However, rates of atrophy are estimated most accurately by performing serial measurements in the same individuals. METHODS: MRI-based volumetric measurements of the hippocampi and temporal horns were performed in 24 cognitively normal subjects aged 70 to 89 years who were individually matched with respect to gender and age with 24 patients with AD. Each subject underwent an MRI protocol twice, separated by 12 months or more. RESULTS: The mean annual rate of hippocampal volume loss among control subjects was -1.55+/-1.38% and the temporal horns increased in volume by 6.15+/-7.69% per year. These rates were significantly greater among AD patients: hippocampus, -3.98+/-1.92% per year, p < 0.001; temporal horn, 14.16+/-8.47% per year, p = 0.002. CONCLUSION: A statistically significant yearly decline in hippocampal volume and an increase in temporal horn volume was identified in elderly control subjects who represent typical aging individuals. These rates were approximately 2.5 times greater in patients with AD than in individually age- and gender-matched control subjects.

Aged↗

Population-based study of the incidence of sudden unexplained death in epilepsy.

OBJECTIVE: To determine the population-based incidence of sudden unexplained death in epilepsy (SUDEP) and to determine the risk of SUDEP compared with the general population. BACKGROUND: Prior studies of SUDEP have described a wide range of incidence and have suffered from selection bias and other methodologic limitations. A population-based study of the incidence of SUDEP has never been performed. Furthermore, the risk of sudden death in the epilepsy population has not been compared with that of the general population. METHODS: All deaths in persons whose epilepsy was diagnosed between 1935 and 1994 in Rochester, MN, were reviewed. The rate of SUDEP was compared with the expected rate of sudden death in the general population for patients age 20 to 40 years to determine the standardized mortality ratio (SMR). RESULTS: We identified nine cases of SUDEP. SUDEP accounted for 8.6% (7 of 81) of the deaths in persons 15 to 44 years of age. The incidence of SUDEP was 0.35 per 1,000 person-years. SMR for SUDEP was 23.7 (95% confidence interval, 7.7 to 55.0) compared with the general population. CONCLUSIONS: The incidence of SUDEP in our study was 0.35 per 1,000 person-years. SUDEP was responsible for 1.7% of deaths in our cohort. SUDEP is a rare cause of death in the epilepsy population but exceeds the expected rate of sudden death in the general population by nearly 24 times.

Adolescent↗

Olfactory dysfunction in Guamanian ALS, parkinsonism, and dementia.

OBJECTIVES: To assess whether olfactory deficits are present in the general Guamanian Chamorro population and to evaluate olfaction in each of the four neurodegenerative disease syndromes of Guam: ALS, pure parkinsonism, pure dementia, and the combined parkinsonism-dementia complex (PDC). BACKGROUND: Olfactory dysfunction was previously reported in patients with PDC of Guam. METHODS: We developed a culturally adjusted olfactory test battery, derived from the original University of Pennsylvania Smell Identification Test (UPSIT), and administered this to Chamorro residents with ALS (n=9), pure parkinsonism (n=9), pure dementia (n=11), PDC (n=31), and 53 neurologically normal Chamorro and 25 North American control subjects. RESULTS: Similar, marked olfactory dysfunction was found in all four syndromes of Guamanian neurodegenerative disease. This correlated poorly with measures of parkinsonism and cognition. In the neurologically normal Chamorro control group, six subjects (11%) had very low olfactory scores; these were less than the lowest North American score, raising a question of subclinical neurodegenerative disease. CONCLUSIONS: Marked olfactory deficits are common to all four Guamanian neurodegenerative syndromes, and suggest the possibility of similar central neuropathologic substrates. The deficit in the Guamanian ALS group contrasts with idiopathic ALS, in which olfactory function has been reported to be only slightly compromised.

Adult↗

Nonsteroidal anti-inflammatory drug use and Alzheimer's disease: a case-control study in Rochester, Minnesota, 1980 through 1984.

OBJECTIVE: To compare the frequency of use of nonsteroidal anti-inflammatory drugs (NSAIDs) among 302 incident cases of Alzheimer's disease (AD) and age- and sex-matched control subjects. DESIGN: We undertook a retrospective case-control study, using the resources of the Rochester Epidemiology Project. MATERIAL AND METHODS: In ongoing studies of dementia in Rochester, Minnesota, we identified all incident cases of AD with onset between 1980 and 1984. From among all Rochester residents who received care at Mayo Clinic Rochester during those years, we selected one age- (within 3 years) and sex-matched control subject. For this study, exposure to a prescription NSAID was defined as prescribed use for 7 or more days during the 2-year window of time encompassing the year of onset and the year before onset among cases and the corresponding index year and the year prior for control subjects. RESULTS: The odds ratio (OR) for exposure, as described, to a prescription NSAID versus no exposure to any NSAID was 0.79 (95% confidence interval [CI], 0.45 to 1.38); the OR was 1.00 (95% CI, 0.52 to 1.92) for women and 0.40 (95% CI, 0.13 to 1.29) for men. Similarly, the overall OR for aspirin exposure versus no NSAID exposure was 0.90 (95% CI, 0.54 to 1.50). CONCLUSION: These data are suggestive but not confirmatory of a protective effect of NSAIDs for AD.

Aged↗

Clinical and laboratory indices that enhance the diagnosis of postural tachycardia syndrome.

OBJECTIVE: To identify clinical and laboratory indices that improve the diagnosis of the postural tachycardia syndrome (POTS). DESIGN: We assessed associations of orthostatic intolerance by using multivariate regression analysis. MATERIAL AND METHODS: We evaluated autonomic symptoms and autonomic function in 30 patients with POTS, 30 patients with mild orthostatic intolerance, and 19 age- and gender-matched control subjects. Indices of parasympathetic and sympathetic functions were analyzed on the basis of (1) autonomic function tests (head-up tilt), (2) oscillations at respiratory and nonrespiratory frequencies (0.01 to 0.09 Hz) in R-R interval and blood pressure (Wigner distribution), and (3) deterministic component (rescaled range analysis). RESULTS: The four clinical and laboratory indices that independently supported the diagnosis of POTS are as follows: (1) orthostatic heart rate during the first minute of head-up tilt, (2) autonomic deficit (adrenergic autonomic score), (3) loss of spectral powers in R-R interval during head-up tilt at the fifth minute, and (4) severity of orthostatic dizziness, fatigue, palpitations, and shortness of breath. CONCLUSION: Enhancing the sensitivity and specificity of the diagnosis of POTS should be possible by using these four indices. A hyperadrenergic state and distal neuropathy, affecting adrenergic sympathetic cardiovagal fibers, seem to be involved in the pathophysiology of POTS. Certain features suggest brain-stem dysregulation.

Adult↗

Drug-induced parkinsonism as a risk factor for Parkinson's disease: a historical cohort study in Olmsted County, Minnesota.

OBJECTIVE: To investigate whether subjects who experienced a reversible episode of drug-induced parkinsonism have an increased risk of subsequent Parkinson's disease. DESIGN: We undertook a historical cohort study based on the medical records-linkage system of the Rochester Epidemiology Project in Olmsted County, Minnesota. MATERIAL AND METHODS: All subjects in whom drug-induced parkinsonism developed between 1955 and 1990 and was indexed in the medical records-linkage system were identified. In the 24 eligible subjects, follow-up for the subsequent development of Parkinson's disease consisted of a total of 192.7 person-years. The observed number of cases of Parkinson's disease was compared with the expected number of cases in an age- and sex-matched cohort from the general population. RESULTS: In 2 of 24 subjects with drug-induced parkinsonism, Parkinson's disease later developed. A comparison with the expected number of cases in the general population (0.08) yielded a relative risk of 24.3 (95% confidence interval, 2.9 to 87.5; P = 0.006). CONCLUSION: Our findings suggest that drug-induced parkinsonism is associated with an increased risk of Parkinson's disease. Clarification of the mechanisms of this association may have preventive implications.

Adult↗

Relative contributions of incidence and survival to increasing prevalence of adult-onset diabetes mellitus: a population-based study.

This population-based retrospective study investigates temporal trends in adult-onset diabetes mellitus prevalence, incidence, and survival. The complete community-based medical records, including laboratory results, of all Rochester, Minnesota, residents with a clinical diagnosis of diabetes or diabetes-like condition were reviewed to identify incidence cases aged 30 years or more from 1945 to 1989 (n = 1,847) and prevalence cases aged 45 years or more on January 1, 1970 (n = 465), January 1, 1980 (n = 689), or January 1, 1990 (n = 973). Glucose values and case definitions were standardized throughout. Observed 10-year survival for 1970 and 1980 prevalence cases was compared with that expected for Minnesota white populations in 1970 and 1980, respectively. Age-adjusted prevalence rose 65% for men and 37% for women between 1970 and 1990. There were marked differences among prevalence groups in treatment type, the proportion diagnosed using glucose tolerance tests, and the proportion categorized as obese. Relative survival for 1980 prevalence cases was not greater than that for 1970 prevalence cases. Age-adjusted incidence rates rose 47% for men and 26% for women between 1960 and 1965 and 1985 and 1989. These findings emphasize the need for heightened surveillance and intervention to reduce the burden of illness from adult-onset diabetes mellitus in the population.

Age Distribution↗

Risk of dementia among persons with diabetes mellitus: a population-based cohort study.

It is unclear whether persons with diabetes are at increased risk for dementia, including Alzheimer's disease. Existing studies are limited by small sample size, selection bias, and case-control designs. This population-based historical cohort study provides estimates of the risk of dementia and Alzheimer's disease associated with adult onset diabetes mellitus (AODM). The sample included all persons with AODM residing in Rochester, Minnesota, on January 1, 1970, plus all persons diagnosed in Rochester or who moved to Rochester with the diagnosis between January 1, 1970, and December 31, 1984. Individuals were followed through review of their complete medical records from AODM diagnosis until dementia onset, emigration, death, or January 1, 1985. Standardized morbidity ratios for dementia and Alzheimer's disease were calculated, using an expected incidence based on age- and sex-specific rates for the Rochester population. Poisson regression was used to estimate risks for persons with AODM relative to those without. Of the 1,455 cases of AODM followed for 9,981 person-years, 101 developed dementia, including 77 who met criteria for Alzheimer's disease. Persons with AODM exhibited significantly increased risk of all dementia (Poisson regression relative risk (RR) = 1.66, 95% confidence interval (CI) 1.34-2.05). Risk of Alzheimer's disease was also elevated (for men, R = 2.27, 95% CI 1.55-3.31; for women, RR = 1.37, 95% CI 0.94-2.01). These findings emphasize the importance of AODM prevention and prompt additional investigation of the relation between AODM and dementia.

Age Distribution↗

Effect of age and gender on sudomotor and cardiovagal function and blood pressure response to tilt in normal subjects.

Normative data are limited on autonomic function tests, especially beyond age 60 years. We therefore evaluated these tests in a total of 557 normal subjects evenly distributed by age and gender from 10 to 83 years. Heart rate (HR) response to deep breathing fell with increasing age. Valsalva ratio varied with both age and gender. QSART (quantitative sudomotor axon-reflex test) volume was consistently greater in men (approximately double) and progressively declined with age for all three lower extremity sites but not the forearm site. Orthostatic blood pressure reduction was greater with increasing age. HR at rest was significantly higher in women, and the increment with head-up tilt fell with increasing age. For no tests did we find a regression to zero, and some tests seem to level off with increasing age, indicating that diagnosis of autonomic failure was possible to over 80 years of age.

Adolescent↗

Evaluation of heart rate changes: electrocardiographic versus photoplethysmographic methods.

The heart rate (HR) variation to forced deep breathing (HRDB) and to the Valsalva maneuver (Valsalva ratio; VR) are the two most widely used tests of cardiovagal function in human subjects. The HR is derived from a continuously running electrocardiographic (ECG) recording. Recently, HR derived from the arterial waveform became available on the Finapres device (FinapHR), but its ability to detect rapid changes in HR remains uncertain. We therefore evaluated HRDB and VR derived from FinapHR using ECG-derived HR (ECGHR) recordings as the standard. We also compared the averaged HR on Finapres (Finapav) with beat-to-beat Finapres (FinapBB) values. Studies were undertaken in 12 subjects with large HR variations: age, 34.5 +/- 9.3 (SD) years; six males and six females. FinapBB values were superimposable upon ECGHR for both HRDB and VR. In contrast, Finapav failed to follow ECGHR for HRDB and followed HRECG with a lag for the VR. To evaluate statistically how closely FinapHR approximated ECGHR, we undertook regression analysis, using mean values for each subject. To compare the two methods, we evaluated the significance of the difference between test and standard values. For HRDB, FinapBB reproducibly recorded HR (R2 = 0.998), and was significantly (p = 0.001) better than Finapav (R2 = 0.616; p < 0.001). For VR, HRBB generated a VR that was not significantly different from the correct values, while HRav generated a value that was slightly but consistently lower than the correct values (p < 0.001). We conclude that FinapHR reliably records HR variations in the beat-to-beat mode for cardiovascular HR tests.

Adult↗

Comparative chromosome painting between two marsupials: origins of an XX/XY1Y2 sex chromosome system.

Cross-species chromosome painting was used to investigate genome rearrangements between tammar wallaby Macropus eugenii (2n = 16) and the swamp wallaby Wallabia bicolor (2n = 10female symbol/11male symbol), which diverged about 6 million years ago. The swamp wallaby has an XX female:XY1Y2 male sex chromosome system thought to have resulted from a fusion between an autosome and the small original X, not involving the Y. Thus, the small Y1 should represent the original Y and the large Y2 the original autosome. DNA paints were prepared from flow-sorted and microdissected chromosomes from the tammar wallaby. Painting swamp wallaby spreads with each tammar chromosome-specific probe gave extremely strong and clear signals in single-, two-, and three-color FISH. These showed that two tammar wallaby autosomes are represented unchanged in the swamp wallaby, two are represented by different centric fusions, and one by a tandem fusion to make the very long arms of swamp wallaby Chromosome (Chr) 1. The large swamp wallaby X comprises the tammar X as its short arm, and a tandemly fused 7 and 2 as the long arm. The acrocentric swamp wallaby Y2 is a 2/7 fusion, homologous with the long arm of the X. The small swamp wallaby Y1 is confirmed as the original Y by its painting with the tammar Y. However, the presence of sequences shared between the microdissected tammar Xp and Y on the swamp wallaby Y2 implies that the formation of the compound sex chromosomes involved addition of autosome(s) to both the original X and Y. We propose that this involved fusion with an ancient pseudoautosomal region followed by fission proximal to this shared region.

Animals↗

Chromosomal evolution of the Chinese muntjac (Muntiacus reevesi).

The aim of this study was to test the validity of the hypothesis that the 2n=46 karyotype of the Chinese muntjac (Muntiacus reevesi) could have evolved through 12 tandem fusions from a 2n=70 hypothetical ancestral karyotype, which is still retained in Chinese water deer (Hydropotes inermis) and brown-brocket deer (Mazama gouazoubira). Combining fluorescence-activated chromosomal sorting and degenerate oligonucleotide-primed polymerase chain reaction, we generated chromosome-specific DNA paint probes for 13 M. gouazoubira chromosomes and most of the M. reevesi chromosomes with the exception of 18, 19 and X. These paint probes were used for fluorescence in situ hybridisation to chromosomal preparations of M. reevesi, H. inermis and M. gouazoubira. Chromosome-specific paint probes from M. reevesi chromosomes 1-5 and 11 each delineated more than one homologous pair (18 pairs in total) on the metaphases of H. inermis and M. gouazoubira. All the other probes from M. reevesi and probes from M. gouazoubira each hybridised to one pair of homologous chromosomes or regions. The C5 probe, derived from centromeric satellite sequences of M. reevesi, hybridised to the centromeric regions of all chromosomes of these three species. Most interestingly, several non-random interstitial signals, which are apparently localised to the putative fusion points, were found on chromosomes 1-5 and 11 of M. reevesi. Both the reciprocal painting patterns and localisation of the C5 probe demonstrate that M. reevesi chromosomes 1-5 and 11 could have evolved from 18 different ancestral chromosomes through 12 tandem fusions, thus providing direct molecular cytogenetic support for the tandem fusion hypothesis of karyotype evolution in M. reevesi.

Animals↗

Shared DNA sequences between the X and Y chromosomes in the tammar wallaby - evidence for independent additions to eutherian and marsupial sex chromosomes.

Marsupial sex chromosomes are smaller than their eutherian counterparts and are thought to reflect an ancestral mammalian X and Y. The gene content of this original X is represented largely by the long arm of the human X chromosome. Genes on the short arm of the human X are autosomal in marsupials and monotremes, and represent a recent addition to the eutherian X and Y. The marsupial X and Y apparently lack a pseudoautosomal region and show only end-to-end pairing at meiosis. However, the sex chromosomes of macropodid marsupials (kangaroos and wallabies) are larger than the sex chromosomes of other groups, and a nucleolus organizer is present on the X and occasionally the Y. Chromosome painting using DNA from sorted and microdissected wallaby X and Y chromosomes reveals homologous sequences on the tammar X and Y chromosomes, concentrated on the long arm of the Y chromosome and short arm of the X. Ribosomal DNA sequences were detected by fluorescence in situ hybridization on the wallaby Xp but not the Y. Since no chiasmata have been observed in marsupial sex chromosomes, it is unlikely that these shared sequences act as a pseudoautosomal region within which crossing over may occur, but they may be required for end-to-end associations. The shared region of wallaby X and Y chromosomes bears no homology with the recently added region of the eutherian sex chromosomes, so we conclude that independent additions occurred to both sex chromosomes in a eutherian and macropodid ancestor, as predicted by the addition-attrition hypothesis of sex chromosome evolution.

Animals↗

A novel source of highly specific chromosome painting probes for human karyotype analysis derived from primate homologues.

We have established a series of highly specific painting probes for human acrocentric chromosomes. These chromosomes are involved in the formation of the nucleolar organizer region (NOR) and show DNA sequence homologies within their pericentric heterochromatin. To date, these chromosomes have shown considerable cross hybridization in chromosome painting experiments. Our probe set has been established from primate homologues that are not involved in the NOR in that particular species or from species in which highly repetitive sequences have undergone rapid sequence divergence. The new painting probes should be of particular value for automated microscopy, for which highly specific signals are required as they are recorded at low magnification, e.g. when scoring chromosome 21 domains in interphase nuclei.

Animals↗

Response of human hair cortical cells to fractionated radiotherapy.

Hair cortical cell counting (HCCC) represents a non-invasive, in-vivo measure of cell kill in the human integument. Sixty-six patients undergoing conventionally fractionated, external beam radiotherapy for early stage carcinoma of the prostate had groin hair samples counted. This technique is a sensitive and reproducible measure of radiation effect and may have applicability as an in-vivo prediction tool or in the field of biological dosimetry. A repopulative follicular response occurring at 3-4 weeks may explain flattening of the dose response curve.

Dose-Response Relationship, Radiation↗