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M Casey

Publications and source records attributed to M Casey.

At least 37 records · Page 2Linked to original sources

A t(2;19)(p13;p13.2) in a giant invasive cardiac lipoma from a patient with multiple lipomatosis.

Cardiac lipomas occur infrequently but account for a significant portion of rare cardiac tumors. Common cutaneous lipomas have previously been associated with rearrangements of chromosome band 12q15, which often disrupt the high-mobility-group protein gene HMGIC. In this report, we describe the cytogenetic analysis of an unusual giant cardiac lipoma that exhibited myocardial invasion in a patient with a history of multiple lipomatosis (cutaneous lipoma, lipomatous gynecomastia, lipomatous hypertrophy of the interatrial septum, and dyslipidemia). Cytogenetic studies of cells derived from the cardiac lipoma demonstrated no abnormalities of chromosome 12, but did reveal a t(2;19)(p13;p13.2). A liposarcoma-derived oncogene (p115-RhoGEF) previously mapped to chromosome 19 and the low-density lipoprotein receptor gene (LDLR) previously mapped to chromosome band 19p13 were evaluated to determine whether they were disrupted by this translocation. Fluorescence in situ hybridization analyses assigned p115-RhoGEF to chromosome 19 in bands q13.2-q13.3 and mapped the LDLR to chromosome arm 19p in segment 13.2, but centromeric to the t(2;19) breakpoint. Thus, these genes are unlikely to be involved in the t(2;19)(p13;p13.2). Further studies of the regions of chromosomes 2 and 19 perturbed by the translocation in this unusual infiltrating cardiac lipoma will identify gene(s) that participate in adipocyte growth and differentiation and may provide insight into syndromes of multiple lipomatosis.

Chromosomes, Human, Pair 19↗

Remediation of memory disorders in schizophrenia.

BACKGROUND: Memory deficits are commonly experienced by patients with schizophrenia, often persist even after effective psychotropic treatment of psychotic symptoms and have been demonstrated to interfere with many aspects of successful psychiatric rehabilitation. Because of significant impact on functional outcome, effective remediation of cognitive deficits has been increasingly cited as an essential component of comprehensive treatment. Efforts to remediate memory deficits have met with circumscribed success, leaving uncertain whether schizophrenia patients can be taught, without experimental induction, independently to employ semantic encoding or a range of other mnemonic techniques. METHOD: We examined the feasibility of using memory and problem solving teaching techniques developed within educational psychology--techniques which promote intrinsic motivation and task engagement through contextualization and personalization of learning activities--to remediate memory deficits in a group of in-patients with chronic schizophrenia spectrum disorders. RESULTS: Although our memory remediation group significantly improved on the memory remediation task, they did not make greater gains on measures of immediate paragraph recall or list learning than the control groups. CONCLUSIONS: Targeted remediation of memory appears to yield task specific improvement but the gains do not generalize to other memory tasks. Subjects receiving memory remediation failed to independently activate mnemonic encoding strategies learned and used successfully within training tasks to other general measures of verbal learning and memory.

Adult↗

Mutations in the protein kinase A R1alpha regulatory subunit cause familial cardiac myxomas and Carney complex.

Cardiac myxomas are benign mesenchymal tumors that can present as components of the human autosomal dominant disorder Carney complex. Syndromic cardiac myxomas are associated with spotty pigmentation of the skin and endocrinopathy. Our linkage analysis mapped a Carney complex gene defect to chromosome 17q24. We now demonstrate that the PRKAR1alpha gene encoding the R1alpha regulatory subunit of cAMP-dependent protein kinase A (PKA) maps to this chromosome 17q24 locus. Furthermore, we show that PRKAR1alpha frameshift mutations in three unrelated families result in haploinsufficiency of R1alpha and cause Carney complex. We did not detect any truncated R1alpha protein encoded by mutant PRKAR1alpha. Although cardiac tumorigenesis may require a second somatic mutation, DNA and protein analyses of an atrial myxoma resected from a Carney complex patient with a PRKAR1alpha deletion revealed that the myxoma cells retain both the wild-type and the mutant PRKAR1alpha alleles and that wild-type R1alpha protein is stably expressed. However, in this atrial myxoma, we did observe a reversal of the ratio of R1alpha to R2beta regulatory subunit protein, which may contribute to tumorigenesis. Further investigation will elucidate the cell-specific effects of PRKAR1alpha haploinsufficiency on PKA activity and the role of PKA in cardiac growth and differentiation.

Abnormalities, Multiple↗

HMOs serving rural areas: experiences with HMO accreditation and HEDIS reporting.

This article explores the reasons why two groups of health maintenance organizations (HMOs) that serve rural areas have chosen to apply or not to apply for National Committee for Quality Assurance (NCQA) accreditation, and their future plans regarding accreditation. It also describes the challenges faced by HMOs serving rural areas in meeting NCQA accreditation standards and collecting Health Plan Employer Data and Information Set (HEDIS) data. A number of accredited HMOs cited positive benefits of the accreditation process, and most HMOs plan to apply or reapply for accreditation in the near future. Several HMOs identified challenges with accreditation standards, and the majority reported difficulty collecting some HEDIS measures. The HMOs identified a number of accreditation and HEDIS issues that are more problematic in rural areas.

Accreditation↗

Molecular genetic diagnosis of the familial myxoma syndrome (Carney complex).

We describe an individual in whom molecular genetic testing provided a diagnosis of the Carney complex, an autosomal dominant syndrome comprising cutaneous and cardiac myxomas, spotty pigmentation of the skin, and endocrinopathy. Recently, we localized the Carney complex disease gene to chromosome region 17q2. Our patient was a member of a family segregating the Carney complex, but was not, himself, initially thought to be affected. Haplotype analysis based on genotyping studies with 17q2 microsatellites predicted that this individual was, in fact, affected by Carney complex and was at risk for development of myxomas. Further clinical evaluation and re-review of prior pathologic studies, then, confirmed the DNA-based diagnosis. This report highlights the difficulty in establishing a diagnosis of Carney complex based on clinical and pathologic findings alone, and we suggest that molecular genetic analyses provide an important diagnostic method for this familial myxoma syndrome.

Adult↗

Network stability from activity-dependent regulation of neuronal conductances.

Activity-dependent plasticity appears to play an important role in the modification of neurons and neural circuits that occurs during development and learning. Plasticity is also essential for the maintenance of stable patterns of activity in the face of variable environmental and internal conditions. Previous theoretical and experimental results suggest that neurons stabilize their activity by altering the number or characteristics of ion channels to regulate their intrinsic electrical properties. We present both experimental and modeling evidence to show that activity-dependent regulation of conductances, operating at the level of individual neurons, can also stabilize network activity. These results indicate that the stomatogastric ganglion of the crab can generate a characteristic rhythmic pattern of activity in two fundamentally different modes of operation. In one mode, the rhythm is strictly conditional on the presence of neuromodulatory afferents from adjacent ganglia. In the other, it is independent of neuromodulatory input but relies on newly developed intrinsic properties of the component neurons.

Afferent Pathways↗

Activation of tyrosine receptor kinase plays a role in expression of long-term potentiation in the rat dentate gyrus.

Long-term potentiation (LTP) in perforant path-granule cell synapses has been shown to be accompanied by an increase in glutamate release. The objective of this study was to examine the possibility that nerve growth factor (NGF), by activating tyrosine kinase, modulates glutamate release and, therefore, contributes to expression of LTP in dentate gyrus. The data indicate that NGF, in the presence of trans-1-aminocyclopentyl-1,3-dicarboxylate (ACPD), enhanced KCI-stimulated release and KCI-stimulated calcium influx in vitro and that these effects were blocked by the tyrosine receptor kinase (trk) inhibitor tyrphostin AG879. The data also indicate that NGF increased phosphorylation of trkA and the mitogen-activated protein kinase extracellular signal-regulated kinase (ERK) in dentate gyrus in vitro. In addition to its effects in vitro, tyrphostin AG879 inhibited the expression of LTP in perforant path-granule cell synapses and the accompanying increase in transmitter release. Analysis of phosphorylation of the two tyrosine kinase substrates trkA and ERK in synaptosomes prepared from untetanized and tetanized dentate gyrus revealed that LTP was associated with increased phosphorylation of both proteins; no evidence of such a change was observed in either tetanized or untetanized tissue prepared from tyrphostin-pretreated rats. These findings are consistent with the hypothesis that NGF, by interacting with trkA, triggers a sequence of tyrosine kinase-dependent phosphorylation steps that modulate glutamate release and calcium influx and impact on expression of LTP in dentate gyrus.

Animals↗

The rural health care workforce implications of practice guideline implementation.

BACKGROUND: Rural health care workforce forecasting has not included adjustments for predictable changes in practice patterns, such as the introduction of practice guidelines. PURPOSE: To estimate the impact of a practice guideline for a single health condition on the needs of a rural health professional workforce. METHODS: The current care of a cohort of rural Medicare recipients with diabetes mellitus was compared with the care recommended by a diabetes practice guideline. The additional tests and visits that were needed to comply with the guideline were translated into additional hours of physician services and total physician full-time equivalents. RESULTS: The implementation of a practice guideline for Medicare recipients with diabetes in rural Minnesota would require over 30,000 additional hours of primary care physician services and over 5,000 additional hours of eye care professionals' time per year. This additional need represents a 1.3% to 2.4% increase in the number of primary care physicians and a 1.0% to 6.6% increase in the number of eye-care clinicians in a state in which the rural medical provider to population ratios already meet some recommended workforce projections. CONCLUSIONS: The implementation of practice guidelines could result in an increased need for rural health care physicians or other providers. That increase, caused by guideline implementation, should be accounted for in future rural health care workforce predictions.

Aged↗

Identification of a novel genetic locus for familial cardiac myxomas and Carney complex.

BACKGROUND: Intracardiac myxomas are significant causes of cardiovascular morbidity and mortality through embolic stroke and heart failure. In the autosomal dominant syndrome Carney complex, intracardiac myxomas arise in the setting of lentiginosis and other lesions associated with cutaneous hyperpigmentation, extracardiac myxomas, and nonmyxomatous tumors. Genetic factors that regulate cardiac tumor growth remain unknown. METHODS AND RESULTS: We used the molecular genetic techniques of linkage analysis to study 4 kindreds affected by Carney complex to determine the genetic basis of this syndrome. Our investigation confirmed genetic heterogeneity of Carney complex. Moreover, genetic linkage analysis with polymorphic short tandem repeats on the long arm of chromosome 17 revealed maximal pairwise LOD scores of 5.9, 1.5, 1.8, and 2.9 for families YA, YB, YC01, and YC11, respectively. Haplotype analysis excluded a founder effect at this locus. These data identify a major 17 cM locus on chromosome 17q2 that contains the Carney complex disease gene. CONCLUSIONS: The ultimate identification and analysis of the Carney complex disease gene at this human chromosome 17q2 locus will facilitate diagnosis and treatment of cardiac myxomas and will foster new concepts in regulation of cardiac cell growth and differentiation.

Chromosomes, Human, Pair 17↗

Regence HMO Oregon.

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Health Maintenance Organizations↗

Missouri Advantage.

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Health Maintenance Organizations↗

Commentary: Medicaid reform issues affecting the Indian health care system.

Substantial numbers of Indian people rely on Medicaid for their primary health insurance coverage. When state Medicaid programs enroll Indians in managed care programs, several unintended consequences may ensue. This paper identifies some of the perverse consequences of Medicaid reform for Indians and the Indian health care system and suggests strategies for overcoming them. It discusses the desire of Indian people to receive culturally appropriate services, the need to maintain or improve Indian health care system funding, and the duty of state governments to respect tribal sovereignty. Because of their relatively small numbers, Indians may be treated differently under Medicaid managed care systems without significantly endangering anticipated program savings. Failure of Medicaid programs to recognize the uniqueness of Indian people, however, may severely weaken the Indian health care system.

Eligibility Determination↗