| 41. |
- Almqvist, E, et al.
(author)
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Ancestral differences in the distribution of the delta 2642 glutamic acid polymorphism is associated with varying CAG repeat lengths on normal chromosomes : insights into the genetic evolution of Huntington disease.
- 1995
-
In: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 4:2, s. 207-14
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Journal article (peer-reviewed)abstract
- This study addresses genetic factors associated with normal variation of the CAG repeat in the Huntington disease (HD) gene. To achieve this, we have studied patterns of variation of three trinucleotide repeats in the HD gene including the CAG and adjacent CCG repeats as well as a GAG polymorphism at residue 2642 (delta 2642). We have previously demonstrated that variation in the CCG repeat is associated with variation of the CAG repeat length on normal chromosomes. Here we show that differences in the GAG trinucleotide polymorphism at residue 2642 is also significantly correlated with CAG size on normal chromosomes. The B allele which is associated with higher CAG repeat lengths on normal chromosomes is markedly enriched on affected chromosomes. Furthermore, this glutamic acid polymorphism shows significant variation in different ancestries and is absent in chromosomes of Japanese, Black and Chinese descent. Haplotype analysis of both the CCG and delta 2642 polymorphisms have indicated that both are independently associated with differences in CAG length on normal chromosomes. These findings lead to a model for the genetic evolution of new mutations for HD preferentially occurring on normal chromosomes with higher CAG repeat lengths and a CCG repeat length of seven and/or a deletion of the glutamic acid residue at delta 2642. This study also provides additional evidence for genetic contributions to demographic differences in prevalence rates for HD.
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| 42. |
- Almqvist, E, et al.
(author)
-
Geographical distribution of haplotypes in Swedish families with Huntington's disease.
- 1994
-
In: Human Genetics. - 0340-6717 .- 1432-1203. ; 94:2, s. 124-8
-
Journal article (peer-reviewed)abstract
- This study was planned to determine the number of origins of the mutation underlying Huntington's disease (HD) in Sweden. Haplotypes were constructed for 23 different HD families, using six different polymorphisms [(CCG)n, GT70, 674, BS1, E2 and 4.2], including two within the gene. In addition, extensive genealogical investigations were performed, and the geographical origin of the haplotypes was studied. Ten different haplotypes were observed suggesting multiple origins for the HD mutation in Sweden. Analysis of the two polymorphic markers within the HD gene (the CCG repeat and GT70) indicates that there are at least three origins for the HD mutation in Sweden. One of these haplotypes (7/A) accounts for 89% of the families, suggesting that the majority of the Swedish HD families are related through a single HD mutation of ancient origin. Furthermore, three of the families that were previously considered to be unrelated could be traced to a common ancestor in the 15th century, a finding that is consistent with this hypothesis.
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| 43. |
- Almqvist, E, et al.
(author)
-
Risk reversals in predictive testing for Huntington disease.
- 1997
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In: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 61:4, s. 945-52
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Journal article (peer-reviewed)abstract
- The first predictive testing for Huntington disease (HD) was based on analysis of linked polymorphic DNA markers to estimate the likelihood of inheriting the mutation for HD. Limits to accuracy included recombination between the DNA markers and the mutation, pedigree structure, and whether DNA samples were available from family members. With direct tests for the HD mutation, we have assessed the accuracy of results obtained by linkage approaches when requested to do so by the test individuals. For six such individuals, there was significant disparity between the tests. Three went from a decreased risk to an increased risk, while in another three the risk was decreased. Knowledge of the potential reasons for these changes in results and impact of these risk reversals on both patients and the counseling team can assist in the development of strategies for the prevention and, where necessary, management of a risk reversal in any predictive testing program.
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| 44. |
- Almqvist, E, et al.
(author)
-
Screening of amyloid precursor protein gene mutation (APP 717 Val-->Ile) in Swedish families with Alzheimer's disease.
- 1993
-
In: Journal of neural transmission. Parkinson's disease and dementia section. - 0936-3076. ; 6:2, s. 151-6
-
Journal article (peer-reviewed)abstract
- Screening for the APP 717 Val-->Ile mutation in the amyloid precursor protein (APP) gene in 34 Swedish families with familial Alzheimer's disease (FAD), 16 sporadic cases of Alzheimer's disease and five patients with Down's syndrome (DS) failed to identify further cases of the mutation. These results suggests that the mutation is rare among Swedish families with Alzheimer's disease. In addition, we summarize present reports of the frequency of the mutation.
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| 45. |
- Almqvist, Elisabeth W., 1958-
(author)
-
A randomized, placebo-controlled trial of coenzyme Q10 and remacemide in Huntington's disease
- 2001
-
In: Neurology. - : Ovid Technologies (Wolters Kluwer Health). - 0028-3878 .- 1526-632X. ; 57:3, s. 397-404
-
Journal article (peer-reviewed)abstract
- OBJECTIVES: To determine whether chronic treatment with coenzyme Q10 or remacemide hydrochloride slows the functional decline of early Huntington's disease (HD).METHODS: The authors conducted a multicenter, parallel group, double-blind, 2 x 2 factorial, randomized clinical trial. Research participants with early HD (n = 347) were randomized to receive coenzyme Q10 300 mg twice daily, remacemide hydrochloride 200 mg three times daily, both, or neither treatment, and were evaluated every 4 to 5 months for a total of 30 months on assigned treatment. The prespecified primary measure of efficacy was the change in total functional capacity (TFC) between baseline and 30 months. Safety measures included the frequency of clinical adverse events.RESULTS: Neither intervention significantly altered the decline in TFC. Patients treated with coenzyme Q10 showed a trend toward slowing in TFC decline (13%) over 30 months (2.40- versus 2.74-point decline, p = 0.15), as well as beneficial trends in some secondary measures. There was increased frequency of nausea, vomiting, and dizziness with remacemide and increased frequency of stomach upset with coenzyme Q10.CONCLUSIONS: Neither remacemide nor coenzyme Q10, at the dosages studied, produced significant slowing in functional decline in early HD.
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| 46. |
- Almqvist, E W, et al.
(author)
-
A worldwide assessment of the frequency of suicide, suicide attempts, or psychiatric hospitalization after predictive testing for Huntington disease.
- 1999
-
In: American Journal of Human Genetics. - 0002-9297 .- 1537-6605. ; 64:5, s. 1293-304
-
Journal article (peer-reviewed)abstract
- Prior to the implementation of predictive-testing programs for Huntington disease (HD), significant concern was raised concerning the likelihood of catastrophic events (CEs), particularly in those persons receiving an increased-risk result. We have investigated the frequency of CEs-that is, suicide, suicide attempt, and psychiatric hospitalization-after an HD predictive-testing result, through questionnaires sent to predictive-testing centers worldwide. A total of 44 persons (0.97%) in a cohort of 4,527 test participants had a CE: 5 successful suicides, 21 suicide attempts, and 18 hospitalizations for psychiatric reasons. All persons committing suicide had signs of HD, whereas 11 (52.4%) of 21 persons attempting suicide and 8 (44.4%) of 18 who had a psychiatric hospitalization were symptomatic. A total of 11 (84.6%) of 13 asymptomatic persons who experienced a CE during the first year after HD predictive testing received an increased-risk result. Factors associated with an increased risk of a CE included (a) a psychiatric history
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| 47. |
- Almqvist, Elisabeth W., 1958-
(author)
-
Dosage effects of riluzole in Huntington's disease : a multicenter placebo-controlled study.
- 2003
-
In: Neurology. - : Ovid Technologies (Wolters Kluwer Health). - 0028-3878 .- 1526-632X. ; 61:11, s. 1551-6
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Riluzole retards striatal glutamate release and pathologic consequences in neurotoxic animal models of Huntington's disease (HD).OBJECTIVE: To determine the dosage-related impact of riluzole on chorea in HD.METHODS: An 8-week double-blind dose-ranging multicenter study of riluzole was conducted in 63 subjects (32 women, 31 men) with HD who were randomized to receive placebo, riluzole 100 mg/day, or riluzole 200 mg/day. The prespecified outcome measure was change in the total maximal chorea score of the Unified Huntington's Disease Rating Scale (UHDRS).RESULTS: Fifty-six (89%) subjects completed the study. A reduction (p < 0.01) in chorea at 8 weeks was found using a linear trend test with dose. Comparing the groups individually, the reduction in chorea for the riluzole 200-mg/day group (-2.2 +/- 3.3) was different (p = 0.01) from placebo (+0.7 +/- 3.4), but the riluzole 100-mg/day group (-0.2 +/- 2.9) was not. Riluzole did not improve other motor, cognitive, behavioral, or functional components of the UHDRS. Alanine aminotransferase was elevated in a dosage-dependent fashion (p = 0.01).CONCLUSIONS: Over 8 weeks of treatment, riluzole 200 mg/day ameliorated chorea intensity in HD without improving functional capacity or other clinical features of illness. Riluzole 200 mg/day was attended by reversible liver transaminase abnormalities that would require monitoring in long-term studies.
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| 48. |
- Almqvist, E W, et al.
(author)
-
High incidence rate and absent family histories in one quarter of patients newly diagnosed with Huntington disease in British Columbia.
- 2001
-
In: Clinical Genetics. - 0009-9163 .- 1399-0004. ; 60:3, s. 198-205
-
Journal article (peer-reviewed)abstract
- The advent of the direct mutation test for Huntington disease (HD) has made it possible to identify a previously unrecognized symptomatic population of HD, including those with an atypical presentation or patients without a family history of HD. The present study investigated the uptake of this test in the province of British Columbia (BC), Canada and assessed the incidence rate and rate of identification of new mutations for HD. All symptomatic individuals residing in BC who were referred for the genetic test for HD between 1993 and 2000 (n=205) were analyzed for CAG expansion, baseline demographics and clinical data, and a family history of HD. A total of 141 (or 68.8%) had a CAG expansion > or =36. Of these, almost one-quarter (24.1%) did not have a family history of HD. An extensive chart review revealed that 11 patients (or 7.8%) had reliable information on both parents (who lived well into old age) and therefore possibly could represent new mutations for HD. This indicates a three to four times higher new mutation rate than previously reported. Our findings also show that the yearly incidence rate for HD was 6.9 per million, which is two times higher than previous incidence studies performed prior to the identification of the HD mutation. We also identified five persons with a clinical presentation of HD but without CAG expansion (genocopies) (2.4%).
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| 49. |
- Almqvist, E W, et al.
(author)
-
Psychological consequences and predictors of adverse events in the first 5 years after predictive testing for Huntington's disease.
- 2003
-
In: Clinical Genetics. - : Wiley. - 0009-9163 .- 1399-0004. ; 64:4, s. 300-9
-
Journal article (peer-reviewed)abstract
- The promise of genetic medicine is to provide information, based on genotype, to persons not yet sick about their risk of future illness. However, little is known of the long-term psychological effects for asymptomatic persons learning their risk of having a serious disease. Predictive genetic testing for Huntington's disease (HD) has been offered for the longest time for any disease. In the present study, the psychological consequences of predictive testing were assessed prospectively in individuals at risk for HD during seven visits over 5 years. Questionnaires of standard measures of psychological distress (the General Severity Index of the Symptom Check List-90-Revised), depression (the Beck Depression Inventory), and general well-being (the General Well-Being Scale) were administered to the participants. A significant reduction in psychological distress was observed for both result groups throughout 2 years (p < 0.001) and at 5 years (p = 0.002). Despite the overall improvement of the psychological well-being, 6.9% (14 of 202) of the participants experienced an adverse event during the first 2 years after predictive testing that was clinically significant. The frequency of all defined adverse events in the participants was 21.8%, with higher frequency in the increased risk group (p = 0.03) and most occurring within 12 months of receiving results.
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| 50. |
- Alvariza, Anette, et al.
(author)
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A person-centred approach in nursing: Validity and reliability of the Carer Support Needs Assessment Tool
- 2018
-
In: European Journal of Oncology Nursing. - : Elsevier BV. - 1462-3889 .- 1532-2122. ; 35, s. 1-8
-
Journal article (peer-reviewed)abstract
- Purpose: The Carer Support Needs Assessment Tool (CSNAT) was developed for use among family caregivers in palliative care for assessment of their support needs. The purpose of this study was to translate and evaluate the validity and reliability of the CSNAT in a sample of Swedish family caregivers and nurses in a palliative care context. Methods: Data for this validation study was collected during 2016 in the context of palliative home care in two larger Swedish cities. The study was conducted in three stages to reach conceptual, semantic, operational and measurement equivalence between the original UK version and the Swedish version. Stage I consisted of translation to Swedish. In Stage II, cognitive interviews were performed with 8 family caregivers and 10 nurses. Data were analyzed based on relevance, clarity and sensitivity. In Stage III, the CSNAT and related self-rating measures (caregiver burden, preparedness for caregiving and quality of life) were completed by 118 family caregivers. Data quality, construct validity and test-retest reliability were evaluated. Results: The CSNAT items were considered relevant and useful to identify areas of support needs. The Swedish CSNAT showed sound psychometric properties with satisfactory data quality and few problems with missing data across items (1.8%-6.1%). All items except one correlated as expected (rho>0.3) with caregiver burden, supporting construct validity. All items had satisfactory test-retest reliability (κw=0.45-0.75). Conclusions: This study further adds to the validity of the CSNAT and shows in addition that it is reliable and stable for use among family caregivers in palliative care. © 2018 Elsevier Ltd
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