| 1. |
- Abdulle, Sahra, 1970, et al.
(författare)
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CSF neurofilament protein (NFL) - a marker of active HIV-related neurodegeneration.
- 2007
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Ingår i: Journal of neurology. - : Springer Science and Business Media LLC. - 0340-5354 .- 1432-1459. ; 254:8, s. 1026-32
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND METHODS : The light subunit of the neurofilament protein (NFL), a major structural component of myelinated axons, is a sensitive indicator of axonal injury in the central nervous system (CNS) in a variety of neurodegenerative disorders. Cerebrospinal fluid (CSF) NFL concentrations were measured by ELISA (normal < 250 ng/l) in archived samples from 210 HIV-infected patients not taking antiretroviral treatment: 55 with AIDS dementia complex (ADC), 44 with various CNS opportunistic infections/tumours (CNS OIs), 95 without neurological symptoms or signs, and 16 with primary HIV infection (PHI). The effect of highly active antiretroviral treatment (HAART) was studied by repeated CSF sampling in four of the ADC patients initiating treatment. RESULTS : CSF NFL concentrations were significantly higher in patients with ADC (median 2590 ng/l, IQR 780-7360) and CNS OIs (2315 ng/l, 985-7390 ng/l) than in neuroasymptomatic patients (<250 ng/l, <250-300) or PHI (<250 ng/l, <250-280), p < 0.001. Among patients with ADC, those with more severe disease (stage 2-4) had higher levels than those with milder disease (stage 0.5-1), p < 0.01. CSF NFL declined during HAART to the limit of detection in parallel with virological response and neurological improvement in ADC.CSF NFL concentrations were higher in neuroasymptomatic patients with lower CD4-cell strata than higher, p < 0.001. This increase was less marked than in the ADC patients and noted in 26/58 neuroasymptomatic patients with CD4 counts <200/mul compared to 1/37 with CD4-cells >/=200/mul. CONCLUSIONS : The findings of this study support the value of CSF NFL as a useful marker of ongoing CNS damage in HIV infection. Markedly elevated CSF NFL concentrations in patients without CNS OIs are associated with ADC, follow the grade of severity, and decrease after initiation of effective antiretroviral treatment. Nearly all previously suggested CSF markers of ADC relate to immune activation or HIV viral load that do not directly indicate brain injury. By contrast NFL is a sensitive marker of such injury, and should prove useful in evaluating the presence and activity of ongoing CNS injury in HIV infection.
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| 2. |
- Allen, Peter M., et al.
(författare)
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Aberration control and vision training as an effective means of improving accommodation in individuals with myopia.
- 2009
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Ingår i: Investigative Ophthalmology and Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 0146-0404 .- 1552-5783. ; 50:11, s. 5120-5129
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To test the efficacy of a novel dual treatment for improving accommodative accuracy and dynamics in young persons with myopia.METHODS: Ninety-three young persons with myopia (mean spherical equivalent, -3.0 +/- 1.8 D; age 16.8 +/- 2.1 years; spherical aberration +0.06 +/- 0.04 microm) participated in the study. Custom-designed soft contact lenses were used to alter ocular SA to -0.10 microm to improve accommodative accuracy and reduce any lag of accommodation. A vision training regimen was performed for 18 minutes per day for up to 6 weeks to improve speed of dynamic accommodation. Control groups had contact lenses with no added SA and/or no exercises. To avoid any effects of natural levels of negative aberration on the results of the study, all participants who had negative SA were excluded.RESULTS: The treatment contact lenses produced a significant reduction in lag of accommodation (P < 0.05) at all proximal viewing distances measured. The vision training measurement and treatment resulted in a significant increase in distance facility rate for all groups compared with their own baselines (P < 0.05). Near facility rate improved in the vision training treatment group only compared with its baseline (P < 0.05). Both positive and negative response times for distant viewing were significantly shorter in all groups after training compared with their baseline values (P < 0.05). At near, the positive response times were decreased significantly (P < 0.05) in both groups, whereas the negative response times decreased significantly only in the vision training treatment group.CONCLUSIONS: After 3 months, the dual treatments (altering SA and vision training) used in the study were effective in modifying accommodation. The static accommodative response to targets at proximal distances was increased by the altered SA contact lenses and rates of dynamic accommodation improved with vision training.
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| 3. |
- Cinque, Paola, et al.
(författare)
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Cerebrospinal fluid interferon-gamma-inducible protein 10 (IP-10, CXCL10) in HIV-1 infection.
- 2005
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Ingår i: Journal of neuroimmunology. - : Elsevier BV. - 0165-5728. ; 168:1-2, s. 154-63
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Tidskriftsartikel (refereegranskat)abstract
- Interferon-gamma-inducible protein (IP-10 or CXCL10) is a potent chemoattractant and has been suggested to enhance retrovirus infection and mediate neuronal injury. In order to assess this chemokine in central nervous system (CNS) HIV infection, we measured the cerebrospinal fluid (CSF) and plasma concentrations of CXCL10 by immunoassay in samples derived from 97 HIV-infected subjects across a spectrum of immunological progression and CNS complications and from 16 HIV seronegative control subjects studied at three clinical centers between 1994 and 2001. We also examined changes in the CSF and plasma CXCL10 concentrations in 30 subjects starting and three stopping antiretroviral therapy. CSF CXCL10 concentrations: (1) correlated with CSF HIV RNA and white blood cell (WBC) counts, but not with blood CXCL10, HIV RNA, or CD4 counts; (2) were increased in subjects with primary and asymptomatic HIV infections and AIDS dementia complex, but less frequently in those with more advanced infection, with or without CNS opportunistic diseases except cytomegalovirus encephalitis; (3) decreased in subjects starting antiretroviral in association with decreases in CSF and plasma HIV RNA and CSF WBCs; and (4) conversely, increased in subjects stopping treatment in parallel with CSF HIV RNA and WBCs. These results confirm that CSF CXCL10 associates closely with both CSF HIV and WBCs and suggest that this chemokine may be both a response to and contributing determinant of local infection. High CSF levels may be useful in the diagnosis of ADC in subjects with advanced immunosuppression in whom CMV encephalitis has been ruled out, though this issue requires further study.
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| 4. |
- Colleoni, Marco, et al.
(författare)
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Site of primary tumor has a prognostic role in operable breast cancer: the international breast cancer study group experience.
- 2005
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Ingår i: Journal of clinical oncology : official journal of the American Society of Clinical Oncology. - 0732-183X. ; 23:7, s. 1390-400
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Cancer presenting at the medial site of the breast may have a worse prognosis compared with tumors located in external quadrants. For medial tumors, axillary lymph node staging may not accurately reflect the metastatic potential of the disease. PATIENTS AND METHODS: Eight-thousand four-hundred twenty-two patients randomly assigned to International Breast Cancer Study Group clinical trials between 1978 and 1999 were classified as medial site (1,622; 19%) or lateral, central, and other sites (6,800; 81%). Median follow-up was 11 years. RESULTS: A statistically significant difference was observed for patients with medial tumors versus those with nonmedial tumors in disease-free survival (DFS; 10-year DFS, 46% v 48%; HR, 1.10; 95% CI, 1.02 to 1.18; P = .01) and overall survival (10-year OS 59% v 61%; HR, 1.09; 1.01 to 1.19; P = .04). This difference increased after adjustment for other prognostic factors (HR, 1.22; 95% CI, 1.13 to 1.32 for DFS; and HR, 1.24; 95% CI, 1.14 to 1.35 for OS; both P = .0001). The risk of relapse for patients with medial presentation was largest for the node-negative cohort and for patients with tumors larger than 2 cm. In the subgroup of 2,931 patients with negative axillary lymph nodes, 10-year DFS was 61% v 67%, and OS was 73% v 80% for medial versus nonmedial sites, respectively (HR 1.33; 95% CI, 1.15 to 1.54; P = .0001 for DFS; and HR 1.40; 95% CI, 1.17 to 1.67; P = .0003 for OS). CONCLUSION: Tumor site has a significant prognostic utility, especially for axillary lymph node-negative disease, that should be considered in therapeutic algorithms. New staging procedures such as biopsy of the sentinel internal mammary nodes or novel imaging methods should be further studied in patients with medial tumors.
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| 5. |
- Edén, Arvid, 1975, et al.
(författare)
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Immune activation of the central nervous system is still present after >4 years of effective highly active antiretroviral therapy.
- 2007
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Ingår i: The Journal of infectious diseases. - : Oxford University Press (OUP). - 0022-1899 .- 1537-6613. ; 196:12, s. 1779-83
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Tidskriftsartikel (refereegranskat)abstract
- Highly active antiretroviral therapy (HAART) effectively reduces human immunodeficiency virus (HIV) RNA in cerebrospinal fluid (CSF), as well as in plasma. The effect on intrathecal immunoactivation is less well studied. We had earlier found that a substantial number of patients still have evidence of intrathecal immunoactivation after up to 2 years of treatment. We identified 15 patients treated with HAART for > or =4 years who had plasma HIV-RNA levels of <50 copies/mL for > or =3.5 years. CSF samples were available from 10 patients before treatment. We measured white-blood-cell count, HIV-RNA level, neopterin level, and IgG index. During treatment, all patients had HIV-RNA levels of <50 copies/mL in plasma and CSF. In CSF, both neopterin level and IgG index decreased significantly. After 4 years, 9 (60%) of the 15 patients still had neopterin levels in CSF that were above the upper normal reference value (5.8 nmol/L). During HAART, 9 (60%) of the 15 patients had an abnormal IgG index (>0.63). HAART significantly decreases intrathecal immunoactivation, but, despite effective treatment for >4 years, with HIV-RNA levels <50 copies/mL for > or =3.5 years, a substantial proportion of patients continue to show signs of macrophage/microglia activation and intrathecal immunoglobulin production in the CNS.
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| 6. |
- Fleck, Tatjana, et al.
(författare)
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The management of deep sternal wound infections using vacuum assisted closure (V.A.C.) therapy
- 2006
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Ingår i: International Wound Journal. - 1742-481X. ; 3:4, s. 273-280
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Tidskriftsartikel (refereegranskat)abstract
- A group of international experts met in May 2006 to develop clinical guidelines on the practical application of vacuum assisted closure (V.A.C.)+ therapy in deep sternal wound infections. Group discussion and an anonymous interactive voting system were used to develop content. The recommendations are based on current evidence or, where this was not available, the majority consensus of the international group. The principles of treatment for deep sternal wound infections include early recognition and treatment of infection. V.A.C. therapy should be instigated early, following thorough wound irrigation and surgical debridement. V.A.C. therapy in deep sternal wound infections requires specialist surgical supervision and should only be undertaken by clinicians with adequate experience and training in the use of the technique.
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| 7. |
- Giobbie-Hurder, Anita, et al.
(författare)
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Design, conduct, and analyses of Breast International Group (BIG) 1-98: a randomized, double-blind, phase-III study comparing letrozole and tamoxifen as adjuvant endocrine therapy for postmenopausal women with receptor-positive, early breast cancer.
- 2009
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Ingår i: Clinical trials (London, England). - : SAGE Publications. - 1740-7745 .- 1740-7753. ; 6:3, s. 272-87
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Aromatase inhibitors provide superior disease control when compared with tamoxifen as adjuvant therapy for postmenopausal women with endocrine-responsive early breast cancer. PURPOSE: To present the design, history, and analytic challenges of the Breast International Group (BIG) 1-98 trial: an international, multicenter, randomized, double-blind, phase-III study comparing the aromatase inhibitor letrozole with tamoxifen in this clinical setting. METHODS: From 1998-2003, BIG 1-98 enrolled 8028 women to receive monotherapy with either tamoxifen or letrozole for 5 years, or sequential therapy of 2 years of one agent followed by 3 years of the other. Randomization to one of four treatment groups permitted two complementary analyses to be conducted several years apart. The first, reported in 2005, provided a head-to-head comparison of letrozole versus tamoxifen. Statistical power was increased by an enriched design, which included patients who were assigned sequential treatments until the time of the treatment switch. The second, reported in late 2008, used a conditional landmark approach to test the hypothesis that switching endocrine agents at approximately 2 years from randomization for patients who are disease-free is superior to continuing with the original agent. RESULTS: The 2005 analysis showed the superiority of letrozole compared with tamoxifen. The patients who were assigned tamoxifen alone were unblinded and offered the opportunity to switch to letrozole. Results from other trials increased the clinical relevance about whether or not to start treatment with letrozole or tamoxifen, and analysis plans were expanded to evaluate sequential versus single-agent strategies from randomization. LIMITATIONS: Due to the unblinding of patients assigned tamoxifen alone, analysis of updated data will require ascertainment of the influence of selective crossover from tamoxifen to letrozole. CONCLUSIONS: BIG 1-98 is an example of an enriched design, involving complementary analyses addressing different questions several years apart, and subject to evolving analytic plans influenced by new data that emerge over time.
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| 8. |
- Gisslén, Magnus, 1962, et al.
(författare)
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Amyloid and tau cerebrospinal fluid biomarkers in HIV infection.
- 2009
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Ingår i: BMC neurology. - : Springer Science and Business Media LLC. - 1471-2377. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- ABSTRACT: BACKGROUND: Because of the emerging intersections of HIV infection and Alzheimer's disease, we examined cerebrospinal fluid (CSF) biomarkers related of amyloid and tau metabolism in HIV-infected patients. METHODS: In this cross-sectional study we measured soluble amyloid precursor proteins alpha and beta (sAPPalpha and sAPPbeta), amyloid beta fragment 1-42 (Abeta1-42), and total and hyperphosphorylated tau (t-tau and p-tau) in CSF of 86 HIV-infected (HIV+) subjects, including 21 with AIDS dementia complex (ADC), 25 with central nervous system (CNS) opportunistic infections and 40 without neurological symptoms and signs. We also measured these CSF biomarkers in 64 uninfected (HIV-) subjects, including 21 with Alzheimer's disease, and both younger and older controls without neurological disease. RESULTS: CSF sAPPalpha and sAPPbeta concentrations were highly correlated and reduced in patients with ADC and opportunistic infections compared to the other groups. The opportunistic infection group but not the ADC patients had lower CSF Abeta1-42 in comparison to the other HIV+ subjects. CSF t-tau levels were high in some ADC patients, but did not differ significantly from the HIV+ neuroasymptomatic group, while CSF p-tau was not increased in any of the HIV+ groups. Together, CSF amyloid and tau markers segregated the ADC patients from both HIV+ and HIV- neuroasymptomatics and from Alzheimer's disease patients, but not from those with opportunistic infections. CONCLUSIONS: Parallel reductions of CSF sAPPalpha and sAPPbeta in ADC and CNS opportunistic infections suggest an effect of CNS immune activation or inflammation on neuronal amyloid synthesis or processing. Elevation of CSF t-tau in some ADC and CNS infection patients without concomitant increase in p-tau indicates neural injury without preferential accumulation of hyperphosphorylated tau as found in Alzheimer's disease. These biomarker changes define pathogenetic pathways to brain injury in ADC that differ from those of Alzheimer's disease.
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| 9. |
- Gisslén, Magnus, 1962, et al.
(författare)
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Cerebrospinal fluid signs of neuronal damage after antiretroviral treatment interruption in HIV-1 infection.
- 2005
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Ingår i: AIDS research and therapy. - : Springer Science and Business Media LLC. - 1742-6405. ; 2
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The neurofilament is a major structural component of myelinated axons. Increased cerebrospinal fluid (CSF) concentrations of the light chain of the neurofilament protein (NFL) can serve as a sensitive indicator of central nervous system (CNS) injury. To assess whether interrupting antiretroviral treatment of HIV infection might have a deleterious effect on the CNS, we measured NFL levels in HIV-infected subjects interrupting therapy. We identified subjects who had CSF HIV RNA concentrations below 50 copies/mL at the time combination antiretroviral therapy was interrupted, and for whom CSF samples were available before and after the interruption. RESULTS: A total of 8 subjects were studied. The median (range) CSF NFL level at baseline was <125 (<125-220) ng/L (normal <250 ng/L). All 8 subjects exhibited an increase in CSF and plasma HIV RNA after stopping therapy, accompanied by intrathecal immunoactivation as evidenced by CSF lymphocytic pleocytosis (7/8 patients) and increased CSF neopterin concentration (5/6 patients). Three subjects showed a consistent increase in CSF NFL, rising from <125 ng/L to a maximum of 880 (at day 148), 1,010 (day 58) and 10,930 ng/L (day 101). None exhibited new neurological symptoms or signs, or experienced functional deterioration during the period off treatment; of 5 who underwent brief quantitative neurological testing, none showed worsening performance. CONCLUSION: These findings suggest that resurgence of active HIV replication may result in measurable, albeit subclinical, CNS injury. Further studies are needed to define the frequency and pathobiological importance of the increase in CSF NFL.
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| 10. |
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