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P C O'Brien

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

At least 37 records · Page 2Linked to original sources
PubMed2001

Defining the breakpoints of proximal chromosome 14q rearrangements in nine patients using flow-sorted chromosomes.

The breakpoints of deletions and translocations in the proximal chromosome 14q region were defined in nine patients, four of whom have not been reported previously. The aberrant chromosomes were isolated by flow cytometry and used to map the chromosome 14 deletion or translocation breakpoints. The parental origins of deletions were ascertained as paternal in five cases and maternal in one. With the draft genomic sequence for human chromosome 14 available, gene searches were performed on selected intervals of the 14q11.2-q21 region to identify candidate genes for the observed phenotype in some of those affected. Gain of function of the gene PAX9 on chromosome 14 is a possible candidate for a t(14;18) patient affected with mesomelic bone dysplasia. Furthermore, a compilation of other human chromosome 14q proximal deletion and translocation cases was obtained from a search on cytogenetic databases. These findings suggest a locus for myelofibrosis at chromosome 14q13. This study contributes to useful information for identifying disease genes in this region.

Child↗
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

Use and costs of medical care for children and adolescents with and without attention-deficit/hyperactivity disorder.

CONTEXT: A shortage of data exists on medical care use by persons with attention-deficit/hyperactivity disorder (ADHD). OBJECTIVE: To compare medical care use and costs among persons with and without ADHD. DESIGN AND SETTING: Population-based cohort study conducted in Rochester, Minn. SUBJECTS: All children born in 1976-1982 were followed up through 1995, using school and medical records to identify those with ADHD. The 4880 birth cohort members (mean age, 7. 3 years) still residing in Rochester in 1987 were followed up in medical facility-linked billing databases until death, emigration, or December 31, 1995. MAIN OUTCOME MEASURES: Clinical diagnoses, likelihood and frequency of inpatient and outpatient hospitalizations, emergency department (ED) visits, and total medical costs (including ambulatory care), compared among individuals with and without ADHD. RESULTS: Among the 4119 birth cohort members who remained in the area through 1995 (mean age, 15.3 years), 7.5% (n = 309) had met criteria for ADHD. Compared with persons without ADHD, those with ADHD were more likely to have diagnoses in multiple categories, including major injuries (59% vs 49%; P<.001) and asthma (22% vs 13%; P<.001). The proportion with any hospital inpatient, hospital outpatient, or ED admission was higher for persons with ADHD vs those without ADHD (26% vs 18% [P<. 001], 41% vs 33% [P =.006], and 81% vs 74% [P =.005], respectively). The 9-year median costs for persons with ADHD compared with those without ADHD were more than double ($4306 vs $1944; P<.001), even for the subset with no hospital or ED admissions (eg, median 1987 costs, $128 vs $65; P<.001). The differences between individuals with and without ADHD were similar for males and females and across all age groups. CONCLUSION: In our cohort, compared with persons without ADHD, those with ADHD exhibited substantially greater use of medical care in multiple care delivery settings.

Adolescent↗
PubMed2001

Hippocampal atrophy correlates with clinical features of Alzheimer disease in African Americans.

CONTEXT: Imaging measurements may aid in the characterization and diagnosis of patients with Alzheimer disease (AD). Most research studies, however, have been performed on predominantly white study groups despite the fact that there may be biological differences in AD between African American and white patients. OBJECTIVE: To measure hippocampal volume in African American patients with AD and to correlate these measurements with the presence of AD and neuropsychological test performance. DESIGN: Survey study. SETTING: Academic center. PARTICIPANTS: Fifty-four healthy African American subjects and 32 African American patients with AD were studied. Hippocampal volumes were measured in all subjects from magnetic resonance images using established methods. MAIN OUTCOME MEASURE: Correlations were assessed between hippocampal volume and demographic variables, clinical group membership, and neuropsychological performance. RESULTS: The hippocampi of patients were atrophic with respect to those of healthy subjects (P<.01). Significant direct correlations were present between hippocampal volumes and performance on several different neuropsychological tests (r>0.5 and P<.01 for every test evaluated) when patients and healthy subjects were combined. CONCLUSIONS: Hippocampal atrophy is a feature of AD in African Americans as it is in white subjects. The neuropsychological-hippocampal volume correlations indicate that hippocampal volume measurements do represent a measure of the structural substrate of functional impairment in AD.

Black or African American↗
PubMed2001

Cross-species color banding in ten cases of myeloid malignancies with complex karyotypes.

Cross-species color banding is a multiple-color fluorescence in situ hybridization (FISH) technique using probes developed from other animal species. Hybridization to human metaphases produces color banding patterns specific for each homologous chromosome pair. The technique has been evaluated in a complementary manner with G-banding and chromosome painting in a series of 10 myeloid malignancies with complex or unresolved karyotypes. Color banding detected the majority of chromosomal abnormalities, which had been identified by G-banding and in each case revealed chromosomal changes that G-banding had not identified. Painting was necessary to confirm these abnormalities due to the limitation of only seven colors in the color-banded karyotype. At the same time, painting fortuitously uncovered cryptic abnormalities in 6 of 10 cases that had not been detected by color banding. Insertions were visible by painting only. This study has demonstrated that in the analysis of complex karyotypes, the application of color banding revealed the involvement of the long arm of chromosome 3, indicating a poor risk, in two cases not identified by G-banding. Therefore, these techniques applied together have revealed cryptic chromosomal abnormalities with prognostic significance, which in some cases may have implications for patient management.

Adolescent↗
PubMed2001

A classification efficiency test of spectral karyotyping and multiplex fluorescence in situ hybridization: identification of chromosome homologies between Homo sapiens and Hylobates leucogenys.

Two digital fluorescence microscopy systems, spectral karyotyping (SKY) and multiplex fluorescence in situ hybridisation (M-FISH), are used with multicolour probe sets to assist in the detection of chromosome aberrations. We have compared the resolution of the two methods in their ability to identify karyotype rearrangements, which have occurred during the divergence of Homo sapiens and Hylobates leucogenys in evolution. A 24-color human paint kit distinguishes 74 conserved autosomal segments in H. leucogenys, some of which are difficult to resolve. We examined the extent to which the SKY and M-FISH techniques are able to detect the smallest of these bands. We have found this to be a rigorous test of multicolour chromosome classification systems. We conclude from our results that both systems are able invariably to classify the majority of conserved segments but differ in the efficiency of detection of small inserts.

Animals↗
PubMed2001

FLAIR histogram segmentation for measurement of leukoaraiosis volume.

The purposes of this study were to develop a method to measure brain and white matter hyperintensity (leukoaraiosis) volume that is based on the segmentation of the intensity histogram of fluid-attenuated inversion recovery (FLAIR) images and to assess the accuracy and reproducibility of the method. Whole-head synthetic image phantoms with manually introduced leukoaraiosis lesions of varying severity were constructed. These synthetic image phantom sets incorporated image contrast and anatomic features that mimicked leukoaraiosis found in real life. One set of synthetic image phantoms was used to develop the segmentation algorithm (FLAIR-histoseg). A second set was used to measure its accuracy. Test retest reproducibility was assessed in 10 elderly volunteers who were imaged twice. The mean absolute error of the FLAIR-histoseg method was 6.6% for measurement of leukoaraiosis volume and 1.4% for brain volume. The mean test retest coefficient of variation was 1.4% for leukoaraiosis volume and 0.3% for brain volume. We conclude that the FLAIR-histoseg method is an accurate and reproducible method for measuring leukoaraiosis and whole-brain volume in elderly subjects.

Aged↗
PubMed2001

The relation of glycaemia to the risk of development and progression of retinopathy in the Diabetic Control and Complications Trial.

AIMS/HYPOTHESIS: We have assessed the relation between the quarterly capillary glucose profile and the risk of the development and progression of retinopathy in the DCCT. METHODS: Seven point (preprandial and 90-min postprandial for each meal and bedtime) capillary glucose data were analysed from volunteers whose collections were complete in 80 %, or more, of quarterly periods and who were in the study longer than 4 years (n = 296, conventional therapy; n = 269, intensive therapy). The study cohort differed from excluded patients in having more women and lower HbA(1c) at baseline and fewer adolescents, older age and lower baseline mean blood glucose in the intensive therapy group. RESULTS: Univariate analysis showed significant (p < 0.01) associations to sustained 3-step change in retinopathy of each updated glycaemic parameter: mean blood glucose, mean preprandial glucose, mean postprandial glucose, each preprandial, postprandial and bedtime glucose; range glucose, standard deviation glucose; M-value of Schlichtkrull and mean amplitude of glycaemic excursions, albeit with relatively small hazard ratios. Multivariate analyses showed updated mean blood glucose to be the primary risk factor (p < 0.001) with a weak contribution of mean amplitude of glycaemic excursions at baseline (p < 0.005); no other variables added significantly to the model. The association between updated mean blood glucose and risk for retinopathy was nonlinear: risk progressively increased above updated mean blood glucose of 8.3 mmol/l. A gradient of risk could not be determined below this level because events were few. CONCLUSION/INTERPRETATION: Within the limitations provided by quarterly 7-point capillary glucose measurements as an expression of overall glycaemic behaviour, the major risk for progression of retinopathy is conveyed by updated mean blood glucose especially above 8.3 mmol/l.

Adolescent↗
PubMed2001

Reciprocal chromosome painting between a New World primate, the woolly monkey, and humans.

We employed fluorescence-activated chromosome sorting (FACS) to construct chromosome paint sets for the woolly monkey (Lagothrix lagotricha) and then FISH to reciprocally paint human and woolly monkey metaphases. Reciprocal chromosome painting between humans and the woolly monkey allowed us to assign subchromosomal homologies between these species. The reciprocal painting data between humans and the woolly monkey also allow a better interpretation of the chromosomal difference between humans and platyrrhines, and refine hypotheses about the genomic rearrangements that gave origin to the genome of New World monkeys. Paints of woolly monkey chromosomes were used to paint human metaphases and forty-five clear signals were detected. Paints specific to each human chromosome were used to paint woolly monkey metaphases. The 23 human paints gave 39 clear signals on the woolly monkey karyotype. The woolly monkey chromosomes painted by human paints produced 7 associations of segments homologous to human chromosomes or human chromosome segments: 2/16, 3/21, 4/15, 5/7, 8/18, 10/16 and 14/15. A derived translocation between segments homologous to human chromosomes 4 and 15 is a synapomorphic marker linking all Atelines. These species may also be linked by fragmentation of homologs to human 1, 4, and 15.

Animals↗
PubMed2001

Molecular cytogenetic characterization of the EBV-producing cell line B95-8 (Saguinus oedipus, Platyrrhini) by chromosome sorting and painting.

The cell line B95-8 releases Epstein-Barr virus (EBV) with high titres of transforming activity and is widely used as a model in cancer research and virology. There are, however, controversial reports about the species of origin, cell line stability and karyotype. To address these questions, B95-8 chromosomes were analysed by chromosome sorting and painting by multicolour fluorescence in-situ hybridization. Reciprocal painting was performed between B95-8, 'wildtype' New World monkey and human chromosomes. Saguinus oedipus was revealed as the species of origin. A further five cell-line-specific marker chromosomes, resulting from translocations, deletions and an insertion were found. Although human chromosome 6 or 13 homologues were always involved in these rearrangements, co-hybridization of an EBV-specific DNA probe did not reveal site-specific hybridization to marker chromosomes or at translocation breakpoints. The multicolour probe set described here will be of special value for further evolutionary studies in New World monkeys.

Animals↗
PubMed2001

Karyotype relationships between distantly related marsupials from South America and Australia.

Reciprocal chromosome painting and G-banding were used to compare the karyotypes of three Australian marsupials (Sminthopsis crassicaudata, Macropus eugenii, Trichosurus vulpecula) and one South American marsupial (Monodelphis domestica). The results revealed only a limited number of rearrangements between these species and that the four karyotypes can be described as different combinations of fifteen conserved segments. Five chromosomes are totally conserved between M. domestica (pairs 1, 2, 5, 8 and the X) and the presumed 2n = 14 Australian ancestral karyotype, while M. domestica pairs 3 and 6 and 4 and 7 would have been involved in fusion/fission rearrangements. Chromosome comparisons are presented in a chromosome homology map. Although the species studied diverged 70 million years ago, the karyotype of Monodelphis domestica is highly conserved in relation to those of Australian marsupials.

Animals↗
PubMed2001

Chromosomal painting detects non-random chromosome arrangement in dasyurid marsupial sperm.

Chromosome arrangements have been studied in metaphase and interphase somatic cells and in sperm of many animal species, but there are conflicting data and it is still not clear whether chromosomes are arranged randomly or non-randomly. We used chromosome painting to reveal the positions of chromosomes in marsupial sperm. Marsupials are ideally suited for these studies because they have only a few large chromosomes. Here, we show that chromosomes occupy fixed positions in the immature and mature sperm of Sminthopsis crassicaudata. We suggest that the non-random arrangement of chromosomes in marsupial sperm may be important in establishing chromosome arrangement and patterns of gene activity within the developing embryo.

Animals↗
PubMed2001

Mild cognitive impairment and Alzheimer disease: regional diffusivity of water.

PURPOSE: To compare the regional diffusivity of water in the brains of normally aging elderly people and patients with mild cognitive impairment (MCI) or Alzheimer disease. MATERIALS AND METHODS: Magnetic resonance images were obtained in 21 patients with Alzheimer disease, 19 patients with MCI, and 55 normally aging elderly control subjects without evidence of cognitive impairment. Regions of interest were drawn to compare the apparent diffusion coefficient (ADC) and the anisotropy index (AI) in frontal, parietal, temporal, occipital, anterior, and posterior cingulate white matter (WM), and the thalami and hippocampi. RESULTS: Hippocampal ADC was higher in MCI and Alzheimer disease patients than in control subjects. ADC of the temporal stem and posterior cingulate, occipital, and parietal WM was higher in Alzheimer disease patients than in control subjects. Except for occipital AI, which was lower in MCI patients than in control subjects, there were no differences in AI among the three groups for any of the regions. CONCLUSION: Hippocampal ADC was significantly different between control subjects and MCI patients, many of whom likely have preclinical Alzheimer disease. Elevation in hippocampal ADC may reflect early ultrastructural changes in the progression of Alzheimer disease.

Aged↗
PubMed2001

Phylogenetic implications of the 38 putative ancestral chromosome segments for four canid species.

Chromosome homologies between the Japanese raccoon dog (Nectereutes procyonoides viverrinus, 2n = 39 + 2-4 B chromosomes) and domestic dog (Canis familiaris, 2n = 78) have been established by hybridizing a complete set of canine paint probes onto high-resolution G-banded chromosomes of the raccoon dog. Dog chromosomes 1, 13, and 19 each correspond to two raccoon dog chromosome segments, while the remaining 35 dog autosomes each correspond to a single segment. In total, 38 dog autosome paints revealed 41 conserved segments in the raccoon dog. The use of dog painting probes has enabled integration of the raccoon dog chromosomes into the previously established comparative map for the domestic dog, Arctic fox (Alopex lagopus), and red fox (Vulpes vulpes). Extensive chromosome arm homologies were found among chromosomes of the red fox, Arctic fox, and raccoon dog. Contradicting previous findings, our results show that the raccoon dog does not share a single biarmed autosome in common with the Arctic fox, red fox, or domestic cat. Comparative analysis of the distribution patterns of conserved chromosome segments revealed by dog paints in the genomes of the canids, cats, and human reveals 38 ancestral autosome segments. These segments could represent the ancestral chromosome arms in the karyotype of the most recent ancestor of the Canidae family, which we suggest could have had a low diploid number, based on comparisons with outgroup species.

Animals↗
PubMed2001

Lymph node-positive prostate cancer: evaluation of the results of the combination of androgen deprivation therapy and radiation therapy.

OBJECTIVE: To evaluate the outcome of patients with pathologic stage IV prostate cancer treated with androgen ablation plus external-beam radiation therapy. PATIENTS AND METHODS: Sixty consecutive patients treated between August 1986 and February 1995 with androgen ablation plus radiation therapy for stage IV (T1-4 N1 M0) adenocarcinoma of the prostate were selected for outcome analysis in this retrospective study. Bilateral pelvic lymphadenectomy was performed in 56 patients (93%). The 4 remaining patients had pelvic adenopathy on computed tomography, which was confirmed histologically in all patients. The median pretreatment prostate-specific antigen (PSA) level was 28.8 ng/mL (mean, 55 ng/ mL; range, 0.1-428 ng/mL). All patients received radiation therapy to the prostate, and 29 (48%) had pelvic node radiation. Biochemical failure was defined according to the American Society for Therapeutic Radiology and Oncology criteria of 3 successive increases in the PSA level. RESULTS: The median follow-up duration for surviving patients was 101.1 months (range, 20-134 months). Biochemical failure with (in 2 patients) or without (in 10 patients) clinically evident disease relapse was noted in 12 patients (20%). Four additional patients (7%) had clinical relapse without biochemical failure. Local recurrences were observed in 6 patients (10%), and this clinical impression was confirmed by biopsy in 4 patients. Thirteen patients (22%) died of causes related to prostate cancer. The biochemical relapse-free, clinical disease-free, overall, and cause-specific survival rates at 5 years were 82%, 84%, 76%, and 80%, respectively. CONCLUSIONS: This observational case series of patients treated with the combination of external-beam radiation therapy and permanent androgen ablation for pathologic stage IV prostate cancer suggests that the addition of androgen deprivation therapy to radiation therapy may improve disease outcome. In the absence of randomized trial results, these observations may be beneficial in clinical decision making.

Adenocarcinoma↗
PubMed2001

Elevated gonadotropin levels in patients with Alzheimer disease.

OBJECTIVE: To determine whether gonadotropin levels are elevated in patients with Alzheimer disease (AD). PATIENTS AND METHODS: We measured luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels from stored plasma samples from 284 patients seen at a tertiary care center. We also reviewed their medical charts to record age and estrogen use in the women. The primary aim of our study was to determine whether gonadotropin levels were elevated in 134 patients with AD compared with levels from 45 patients with frontotemporal dementia (FTD) and 105 cognitively normal controls. RESULTS: Although overlap between LH and FSH levels was considerable, LH (P=.046) and FSH (P=.007) were significantly elevated in estrogen-free women with AD (LH: median, 26.3 IU/L; interquartile range, 14.9-34.6 IU/ L; FSH: median, 62.0 IU/L; interquartile range, 45.9-78.5 IU/L) compared with normal controls (LH: median, 20.1 IU/L; interquartile range, 13.7-25.3 IU/L; FSH: median, 47.7 IU/L; interquartile range, 34.1-57.5 IU/L). Levels of LH were also significantly higher (P=.03) in estrogen-free women with AD compared with women with FTD (LH: median, 20.7 IU/L; interquartile range, 19.0-28.5 IU/L; FSH: median, 53.3 IU/L; interquartile range, 27.6-77.9 IU/ L). When we controlled for age, no differences in LH and FSH were observed in men with AD compared with normal controls. CONCLUSIONS: Gonadotropin levels are elevated in some patients with AD, ie, women not taking estrogen. Elevated gonadotropin levels may have a role in the production of amyloid-beta protein, which is related to formation of senile plaques. Therefore, elevated gonadotropin levels may be involved in the pathogenesis of AD.

Aged↗