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J Grigsby

Publications and source records attributed to J Grigsby.

At least 19 recordsLinked to original sources
PubMed2006

Molecular and imaging correlates of the fragile X-associated tremor/ataxia syndrome.

OBJECTIVES: To assess changes in regional brain volumes associated with the fragile X-associated tremor/ataxia syndrome (FXTAS) and the molecular correlates of these changes. METHODS: We administered molecular, MRI, and neurocognitive tests to 36 male premutation carriers (ages 51 to 79), 25 affected and 11 unaffected with FXTAS, and to 21 control subjects of similar age and education. RESULTS: We found differences among the three groups in whole brain, cerebrum, cerebellum, ventricular volume, and whole-brain white matter hyperintensity, with the affected group showing significantly more pathology than the control and unaffected groups. Brainstem volume was significantly smaller in the unaffected group vs controls but did not differ from the affected group. Within the premutation sample, CGG repeat length correlated with reductions in IQ and cerebellar volume and increased ventricular volume and whole-brain white matter hyperintensity. CONCLUSIONS: The current findings, coupled with recent evidence linking the degree of neuropathology (numbers of intranuclear inclusions) to the size of the premutation allele, provide evidence that the neurodegenerative phenotype in the fragile X-associated tremor/ataxia syndrome is a consequence of the CGG repeat expansion.

Aged↗
PubMed2005

Neuropathology of fragile X-associated tremor/ataxia syndrome (FXTAS).

Fragile X-associated tremor/ataxia syndrome (FXTAS) is an adult-onset neurodegenerative disorder that affects carriers, principally males, of premutation alleles (55-200 CGG repeats) of the fragile X mental retardation 1 (FMR1) gene. Clinical features of FXTAS include progressive intention tremor and gait ataxia, accompanied by characteristic white matter abnormalities on MRI. The neuropathological hallmark of FXTAS is an intranuclear inclusion, present in both neurons and astrocytes throughout the CNS. Prior to the current work, the nature of the associations between inclusion loads and molecular measures (e.g. CGG repeat) was not defined. Post-mortem brain and spinal cord tissue has been examined for gross and microscopic pathology in a series of 11 FXTAS cases (males, age 67-87 years at the time of death). Quantitative counts of inclusion numbers were performed in various brain regions in both neurons and astrocytes. Inclusion counts were compared with specific molecular (CGG repeat, FMR1 mRNA level) and clinical (age of onset, age of death) parameters. In the current series, the three most prominent neuropathological characteristics are (i) significant cerebral and cerebellar white matter disease, (ii) associated astrocytic pathology with dramatically enlarged inclusion-bearing astrocytes prominent in cerebral white matter and (iii) the presence of intranuclear inclusions in both brain and spinal cord. The pattern of white matter pathology is distinct from that associated with hypertensive vascular disease and other diseases of white matter. Spongiosis was present in the middle cerebellar peduncles in seven of the eight cases in which those tissues were available for study. There is inclusion formation in cranial nerve nucleus XII and in autonomic neurons of the spinal cord. The most striking finding is the highly significant association between the number of CGG repeats and the numbers of intranuclear inclusions in both neurons and astrocytes, indicating that the CGG repeat is a powerful predictor of neurological involvement in males, both clinically (age of death) and neuropathologically (number of inclusions).

Age of Onset↗
PubMed2004

Fragile-X-associated tremor/ataxia syndrome (FXTAS) in females with the FMR1 premutation.

We describe five female carriers of the FMR1 premutation who presented with symptoms of tremor and ataxia and who received a diagnosis of definite or probable fragile-X-associated tremor/ataxia syndrome (FXTAS). Unlike their male counterparts with FXTAS, none of the women had dementia. Females had not been reported in previous studies of FXTAS, suggesting that they may be relatively protected from this disorder. Brain tissue was available from one of the five subjects, a women who died at age 85 years; microscopic examination revealed intranuclear neuronal and astrocytic inclusions, in accord with the findings previously reported in males with FXTAS. The work-up of families with the FMR1 mutation should include questions regarding neurological symptoms in both older male and female carriers, with the expectation that females may also manifest the symptoms of FXTAS, although more subtly and less often than their male counterparts.

Adult↗
PubMed2004

Aging in individuals with the FMR1 mutation.

Individuals with fragile X mental retardation 1 (FMR1) premutation (55 to 200 CGG repeats) are typically unaffected by fragile X syndrome. However, a subgroup of older males with the premutation have developed a neurological syndrome, which usually begins between 50 and 70 years and is associated with a progressive intention tremor and/or ataxia manifested by balance problems, frequent falling, and Parkinsonian symptoms, such as masked facies, intermittent resting tremor, and mild rigidity. This finding has been termed the fragile X-associated tremor/ataxia syndrome (FXTAS) and has brought focus to the aging process in individuals with the FMR1 mutation. The premutation is associated with elevated messenger RNA levels leading to the formation of intranuclear inclusions in neurons and astrocytes associated with FXTAS. This review is a summary of our experience with FXTAS in male carriers of the premutation.

Aged↗
PubMed2001

Intention tremor, parkinsonism, and generalized brain atrophy in male carriers of fragile X.

The authors report five elderly men with the fragile X premutation who had a progressive action tremor associated with executive function deficits and generalized brain atrophy. These individuals had elevated fragile X mental retardation 1 gene (FMR1) messenger RNA and normal or borderline levels of FMR1 protein. The authors propose that elevations of FMR1 messenger RNA may be causative for a neurodegenerative syndrome in a subgroup of elderly men with the FMR1 premutation.

Aged↗
PubMed2000

Osteoblast numbers after calcitonin therapy: a retrospective study of paired biopsies obtained during long-term calcitonin therapy in postmenopausal osteoporosis.

The present study is a retrospective examination of osteoblast indices in human iliac crest bone biopsies from a study on the long-term efficacy of calcitonin. Paired baseline and 2-year biopsies were examined from eight control subjects and 10 treated subjects; treated subjects received 100 MRC units synthetic salmon calcitonin (Calcimar, Armour Pharmaceutical Co, Scottsdale, AZ) injected i.m. sub Q at bedtime. Control patients did not receive a placebo injection. All subjects received 400 units vitamin D(2) p.o. q.d. and 1200 mg CaCO(3) p.o. q.d. When the differences in baseline and 2-year values were analyzed, subjects receiving calcitonin showed no decrease compared with control subjects for the fraction of osteoid surface lined by osteoblasts (ObS/OS) (but were in fact significantly greater, P = 0.04). There was no difference from control subjects in the number of osteoblasts/mm bone surface (NOb/BPm), or mean mineral apposition rate (MAR). Since calcitonin is receiving renewed interest for osteoporosis therapy, these data (derived from paired human biopsies) are valuable since they show that no decrease in osteoblast cell number resulted from long-term calcitonin therapy. Results point to the need for renewed investigation concerning the effect of calcitonin on osteoblast-osteoclast interactions.

Biopsy↗
PubMed2000

Outcome and utilization differences for older persons with stroke in HMO and fee-for-service systems.

OBJECTIVES: To compare treatment and outcomes for older persons with stroke in Medicare health maintenance organizations (HMOs) and fee-for-service (FFS) systems. DESIGN: Inception cohort stratified by payer and followed for 1 year. SETTING: Six HMOs and five FFS systems with large Medicare populations in the West, Midwest, and Eastern United States. PARTICIPANTS: A total of 429 randomly selected stroke patients receiving rehabilitation in nursing homes or rehabilitation hospitals (RHs) from June 1993 to June 1995. MEASUREMENTS: Improvement in activities of daily living (ADLs) during rehabilitation, and ADL recovery, community residence, and utilization until 12 months after stroke. Outcomes were adjusted for premorbid function, marital status, comorbid illness, posthospital function, cognition, psychological problems, and stroke deficits. RESULTS: At baseline, HMO patients were more likely to be married, and less likely to be blind or have psychiatric diagnoses. HMO patients had shorter hospitalizations (P < .001), were less likely to be admitted to RHs (13% vs 85%, P < .001), and received fewer therapy and physician specialist visits (P < .001) but more home health visits (P < .001). During rehabilitation, FFS patients made greater improvement in ADLs (difference, 0.73 ADLs; 95% CI, .37-1.09). At 1 year, there was no difference in ADL recovery (difference, -0.24 ADL; 95% CI, -0.64-0.16), but FFS patients were more likely to reside in the community (adjusted OR, 1.8; 95% CI, 1.1-3.1), and HMO patients were more likely to reside in nursing homes (adjusted OR, 2.4; 95% CI, 1.1-5.5). CONCLUSION: Study findings suggest that short-term functional outcomes and eventual community residence rates are poorer for Medicare HMO patients with stroke than for stroke patients receiving FFS care, consistent with the lower intensity of rehabilitation (in nursing homes vs RHs) and less specialty physician care.

Aged↗
PubMed2000

Results of a meta-analysis of cost-benefit research: is this a question worth asking?

We attempted a meta-analysis of telemedicine research studies of the costs associated with telemedicine. First, we performed a search of six well known databases with a variety of relevant keywords. After discarding non-English publications, books and duplicate publications resulting from the same study, we were left with 551 articles for analysis. Our second step was to separate the articles into two groups: those with and those without quantitative cost data. Only 38 articles contained any type of real data. Because many of these 38 studies proved to be inadequately designed or conducted, we were unable to perform a traditional meta-analysis. Furthermore, there were a number of disturbing features common to these studies, including the omission of the number of consultations or patients, almost non-existent longitudinal data collection and lack of uniformity in cost analyses. We conclude that it is premature for any statements to be made, either positive or negative, regarding the cost-effectiveness of telemedicine in general.

Cost-Benefit Analysis↗
PubMed1998

Telemedicine: where it is and where it's going.

The term telemedicine encompasses a wide range of telecommunications and information technologies and many clinical applications, although interactive video may be the most common medium. The first telemedicine programs were established almost 40 years ago, but the technology has grown considerably in the past decade. Despite the expansion of telemedicine, the volume of patients receiving services that use the technology remains relatively low (about 21000 in 1996). In part, this reflects the lack of a consistent coverage and payment policy and concerns about licensure, liability, and other issues. A considerable amount of federal funding has supported telemedicine in recent years, and legislators and federal, regional, and state policymakers are struggling with several crucial policy matters. Research on the effectiveness of telemedicine is somewhat limited, although the work that has been done thus far supports the hypothesis that, in general, the technology is medically effective. The cost-effectiveness of specific telemedicine applications has not yet been rigorously demonstrated.

Humans↗
PubMed1998

Higher instrumental activities of daily living disability in Hispanics compared with non-Hispanic whites in rural Colorado. The San Luis Valley Health and Aging Study.

This study examined Hispanic versus non-Hispanic white patterns of needing assistance with instrumental activities of daily living (IADL). The authors interviewed 798 Hispanic and 614 non-Hispanic white residents of rural Colorado, who were aged 60 years and older between 1993 and 1995. Seventy-five participants were nursing home residents at the time of the interview. Community-dwelling Hispanics were 1.6 times as likely as non-Hispanic whites to need assistance with at least one IADL task (95% confidence interval 1.25-2.13). A larger proportion of disabled non-Hispanic whites were in nursing homes but, after including nursing home residents, Hispanics remained significantly more likely to need assistance on at least one IADL task (odds ratio = 1.49, 95% confidence interval 1.16-1.93). Hispanics were also more likely to have difficulty on observed performance tasks. The Hispanic excess was not removed by adjusting for chronic disease, reported difficulty walking, or income. English language proficiency adjustment lowered the Hispanic excess, but adjusting for years of education or Mini-Mental State Examination scores more completely removed the ethnic differences. Higher education was protective for both Hispanic and non-Hispanic white elderly. Efforts to further investigate what facets or correlates of education are operating may offer useful insights into limiting IADL difficulties in future cohorts.

Activities of Daily Living↗
PubMed1998

Telephones, telemedicine, and a technologically neutral coverage policy.

Health care must be understood in a way that facilitates a rational, consistent coverage and payment policy. Telephone care, telemedicine care, and in-person consultation are all useful ways of providing health care services. Because improved health and reasonable costs are the universally desired outcomes of medical consultations, reimbursement policies should favor the most efficient means of providing care. This view suggests that health care reimbursement should be made technologically neutral. That is, a covered service should produce the best clinical outcome at the lowest possible cost, irrespective of the technology used. The logic and implications of technological neutrality and its application to telemedicine are discussed.

Centers for Medicare and Medicaid Services, U.S.↗
PubMed1998

Predicting outcome of anterior temporal lobectomy using simulated neural networks.

PURPOSE: Anterior temporal lobectomy (ATL) is an important option for treatment of medically refractory seizures. Patient selection is not always clear-cut, and there is inherent morbidity and mortality associated with the invasive and expensive surgical protocols. To determine whether patient selection might be facilitated by application of artificial intelligence, we developed a model that predicted seizure outcome after ATL, using a simulated neural network (SNN). METHODS: Predictions of the model were compared with predictions derived from conventional discriminant function analysis. Neural networks and discriminant functions were devised that would predict the occurrence of both Class 1 outcomes (totally seizure-free), and Class 1 or Class 2 outcomes (nearly or totally seizure-free), using data from 87 patients from three surgical centers. The SNNs and discriminant functions were developed using data from a randomly selected subsample of 65 patients, and both models were cross-validated, using the remaining 22 patients. RESULTS: The discriminant functions showed overall predictive accuracy of 78.5% and 72.7%, while the neural networks demonstrated overall accuracy of 81.8% and 95.4%. CONCLUSIONS: Simulated neural networks show promise as adjuncts to decision-making in the selection of epilepsy surgery patients.

Adolescent↗
PubMed1998

Executive cognitive abilities and functional status among community-dwelling older persons in the San Luis Valley Health and Aging Study.

OBJECTIVES: The purpose of this study was to evaluate the contribution of the executive cognitive functions to self-reported and observed performance of activities of daily living and instrumental activities of daily living. DESIGN: These data were collected as part of a cross-sectional survey of community-dwelling older persons, using statistical sampling, in a two-county area of southern Colorado. SETTING: Participants were interviewed and administered measures of general cognition, depression, executive functioning, and performance of self-care and instrumental activities, either in their homes or at the study clinic. PARTICIPANTS: A total of 1158 community-dwelling persons between the ages of 60 and 99 participated. Of these, 657 were female, 501 were male, 637 were Hispanic, and 521 were non-Hispanic whites. MEASUREMENTS: Subjects were administered the Mini-Mental State Exam (MMSE), a measure of executive functioning (the Behavioral Dyscontrol Scale), the Center for Epidemiologic Studies Depression scale (CES-D), and the Structured Assessment of Independent Living Skills (SAILS, a measure of observed performance of daily tasks). They also were interviewed regarding their reported ADL and IADL status using measures from the Longitudinal Study on Aging. RESULTS: Both general mental status and executive functioning demonstrated statistically significant univariate associations with all seven functional status measures (both self-report and observed performance). In a series of ordinary least squares regression models, executive functioning was a predictor for self-reported ADLs and observed performance of complex IADL tasks such as managing money and medications. Mental status did not predict self-reported functioning but was a predictor of observed performance. Depression was a significant variable for self-report measures but not for observed performance. Executive functioning and general mental status demonstrated some degree of independence from one another. CONCLUSION: Executive functioning is an important determinant of functional status for both self-reported and observed ADLs and IADLs and should be assessed routinely when evaluating the mental status and functional abilities of older people. These results replicate and extend previous research on executive functioning among older persons by examining these factors in a large bi-ethnic community sample.

Activities of Daily Living↗
PubMed1998

Failure by design.

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Attitude of Health Personnel↗