Changes in plasma HIV-RNA and CD4 lymphocyte counts in patients receiving highly active antiretroviral therapy.
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Adult↗
Biomedical subjects
R Capra
Publications and source records attributed to R Capra.
Disease activity in multiple sclerosis studied by weekly triple-dose magnetic resonance imaging.
This study assessed whether dysfunction of the blood-brain barrier is an obligatory early event in lesion formation in multiple sclerosis. Dual-echo and T1-weighted magnetic resonance imaging after the injection of a triple dose (0.3 mmol/kg) of gadolinium-DTPA were obtained from ten patients with relapsing-remitting multiple sclerosis every week for 2 months. Sixty-four newly active lesions were detected by the two techniques. All the 44 new lesions seen on dual-echo scans enhanced during the early phases of their formation: 33 at their first appearance, 10 1 week before their appearance on the dual-echo scans, and one the week thereafter. When the every fourth (monthly) scan was analyzed, a total of 55 newly active lesions were detected (i.e., 14% active lesions would have been missed compared to the number found on weekly scanning). Thirty-one of them were detected by both dual-echo and triple-dose scans, 15 only by enhanced scans, and nine only by dual-echo scans. This study confirms that with highly sensitive magnetic resonance imaging techniques dysfunction of the blood-brain barrier is an obligatory early event in new lesion formation in relapsing-remitting multiple sclerosis.
Adult↗
Elevated concentrations of plasma alpha-melanocyte stimulating hormone are associated with reduced disease progression in HIV-infected patients.
To determine whether concentrations of the anti-inflammatory peptide alpha-melanocyte stimulating hormone (alpha-MSH) are associated with accelerated or reduced disease progression in patients with HIV infection, plasma concentrations of alpha-MSH and two other anticytokine molecules, interleukin-1 receptor antagonist (IL-1 ra) and soluble tumor necrosis factor receptor (s TNF r), were taken repeatedly from HIV-positive patients over a 1-year period. Samples from 87 patients were collected by using special precautions to ensure accurate measurement of the peptide. Alpha-MSH concentrations were determined by radioimmunoassay; IL-1 ra and s TNF r concentrations were measured by using enzyme-linked immunosorbent assays. Clinical and immunologic variables were recorded to determine whether there is an association between cytokine antagonist concentrations and disease progression. Elevated concentrations of circulating alpha-MSH were associated with reduced progression of the disease. Circulating alpha-MSH was greater in non-progressors than in progressors; the association between elevated alpha-MSH and reduced disease progression was even more pronounced in patients with baseline CD4+ T cell counts less than 200/microL. No such association was observed for the other two anticytokine molecules, and there was no significant correlation between the plasma concentration of either cytokine antagonist and alpha-MSH. The present evidence and previous findings indicate that elevated concentrations of alpha-MSH are associated with reduced disease progression in HIV-infected patients.
Adult↗
Correlation between enhancing lesion number and volume on standard and triple dose gadolinium-enhanced brain MRI scans from patients with multiple sclerosis.
We investigated the correlations between numbers and volumes of multiple sclerosis (MS) lesions enhancing on standard dose (SD) and triple dose (TD) gadolinium (Gd)-enhanced brain magnetic resonance imaging (MRI) scans, to clarify whether the measurement of enhancing lesion volumes or the use of TD MRI give additional information which can not be obtained by counting enhancing lesions on SD scans. SD and TD Gd-enhanced brain MRI scans were obtained every month for three months from 40 MS patients. The numbers of total and new enhancing lesions were counted, and the total volumes of enhancing lesions were measured from each of the four scans obtained with the two techniques. Univariate correlations between enhancing lesion numbers and volumes were assessed. The numbers of total and new enhancing lesions seen either on SD or TD scans were significantly correlated (r = 0.91 and 0.93, respectively). The numbers and volumes of total enhancing lesions were significantly correlated on both SD (r = 0.90), and TD (r = 0.89) scans. Moderate correlations were found between the total number of enhancing lesions on SD scans and the average difference between TD and SD scans for total enhancing lesion number (r = 0.66), and between the number of new enhancing lesions on SD scans and the average difference between TD and SD scans for new enhancing lesion number (r = 0.50). Our findings indicate that, both on SD and TD MRI, the counts and the volumes of total and new enhancing lesions are highly correlated, and that lesion counting may suffice to monitor MS activity. On the contrary, this study confirms the usefulness of TD MRI for a more complete assessment of the acute changes occurring in MS patients.
Brain↗
Internal models in the control of posture.
The aim of the paper is to investigate the application of control schemes based on "internal models" to the stabilization of the standing posture. The computational complexities of the control problems are analyzed, showing that muscle stiffness alone is insufficient to carry out the task. The paper also re-visits the concept of the cerebellum as a Smith's predictor.
Journal Article↗
Interferon beta treatment for multiple sclerosis has a graduated effect on MRI enhancing lesions according to their size and pathology.
OBJECTIVE: The ability of recombinant human interferon beta-1a (rh-IFN beta-1a) to suppress multiple sclerosis activity, evaluated from MRI, was assessed across a range of lesions enhancing at different gadolinium-DTPA (Gd) doses and with different sizes. METHODS: Every 4 weeks, standard dose (Sd; 0.1 mmol/kg Gd) and triple dose (Td; 0.3 mmol/kgGd) MRI were obtained from 18 patients with relapsing-remitting multiple sclerosis for 3 months before and 4 months after starting treatment with 44 microgram rh-IFN beta-1a subcutaneously, once a week. RESULTS: The total numbers of enhancing lesions were 145 and 126 on Sd scans and 278 and 192 on the Td scans obtained before and after treatment. The introduction of treatment decreased, on average, the rate of appearance of new enhancing lesions seen on Sd and Td scans by 37% (p<0.001). Treatment effects on new enhancing lesions seen on Td scans was, on average, 28% higher than on those seen on Sd scans. The distribution of lesion sizes on Td scans changed significantly during the treatment period (p=0.05), due to a marked decrease in the number of small lesions. CONCLUSIONS: The effect of 44 microgram rh-IFN beta-1a in reducing multiple sclerosis disease activity, as monitored by Gd enhanced MRI, is not homogeneous, but graduated according to the pathological characteristics and size of the lesions.
Adult↗
A multi-centre longitudinal study comparing the sensitivity of monthly MRI after standard and triple dose gadolinium-DTPA for monitoring disease activity in multiple sclerosis. Implications for phase II clinical trials.
In this study we assessed the safety, efficacy and cost-effectiveness of the use of triple dose gadolinium-DTPA (Gd) in serial monthly brain MRI of patients with multiple sclerosis, such as could be selected for clinical trials. The number of enhancing lesions, the number of new enhancing lesions and the number of active scans were used to evaluate the sensitivity of the contrast-enhanced MRI to disease activity. The dose of Gd, and the effect of introducing a delay between the contrast injection and the scan were both appraised. Every 4 weeks for 3 months, and in two separate sessions, scans were obtained from 40 patients with relapsing-remitting or secondary progressive multiple sclerosis, 5 min (early) and 20 min (delayed) after a standard dose (0.1 mmol/kg) or triple dose (0.3 mmol/kg) Gd injection. There were 435 enhancing lesions (242 of which were new) on the early standard dose scans, 479 (263 new) on the delayed standard dose, 772 (365 new) on the early triple dose and 827 (404 new) on the delayed triple dose. There were 109 scans revealing active disease on the early standard dose scans, 112 on the delayed standard dose, 119 on the early triple dose and 120 on the delayed triple dose. Statistical simulations indicated that the sample sizes needed for both cross-over and parallel-group trials with similar powers are lower if serial monthly triple dose MRI is used. No side-effects were reported and no significant changes in blood test parameters were found throughout the study. This study shows that the serial use of triple dose Gd is safe, and that it increases the sensitivity of serial monthly enhanced MRI in detecting multiple sclerosis activity significantly. Its use should enable preliminary trials of experimental therapies for multiple sclerosis to be conducted in small patient populations, over a short period of time.
Adult↗
A preliminary study comparing the sensitivity of serial monthly enhanced MRI after standard and triple dose gadolinium-DTPA for monitoring disease activity in primary progressive multiple sclerosis.
We performed this study to evaluate and compare the numbers of total and new enhancing lesions detected on serial monthly brain magnetic resonance imaging (MRI) after the injection of a standard dose (SD) and a triple dose (TD) of gadolinium-DTPA (Gd) in patients with primary progressive multiple sclerosis (PPMS). Every 4 weeks for 3 months and in two separate sessions, MRI scans were obtained from 5 patients with PPMS, 5 (early) and 20 minutes (delayed) after SD (0.1 mmol/kg) or TD (0.3 mmol/kg) Gd injection. In 2 patients, T1-weighted scans with a magnetization transfer pulse (MT) after SD and TD injection were also obtained. There were 13 enhancing lesions (5 of which were new) on the early SD scans, 15 (5 new) on the delayed SD scans, 17 (6 new) on the early TD scans and 18 (7 new) on the delayed TD scans. TD MRI scans detected more enhancing lesions than SD scans in 3 patients (two of them were those with the lowest disability). The application of the MT pulse did not change the numbers of enhancing lesions seen after the injection of SD and TD of Gd in the remaining two patients. No side effects were reported and no significant changes in blood test parameters were found throughout the study. Our results suggest that serial monthly TD MRI, delayed scanning, MT T1-weighted scans or their combination, although safe, have a limited role for monitoring disease evolution in patients with PPMS.
Adult↗
A comparison between the sensitivities of 3-mm and 5-mm thick serial brain MRI for detecting lesion volume changes in patients with multiple sclerosis.
In this longitudinal study the authors evaluated the sensitivity of 3-mm and 5-mm magnetic resonance imaging (MRI) of the brain in the detection of lesion load changes over time in multiple sclerosis (MS). The authors also correlated the changes detected with these two techniques with the changes in disability. Eighteen patients with MS underwent two MRI examinations of the brain--one at entrance into the study and one follow-up examination. At both sessions, images with 24 contiguous slices 5 mm thick and another with 40 contiguous axial slices 3 mm thick were consecutively acquired. On the same occasions, the patients' Expanded Disability Status Scale (EDSS) scores were rated. MR images with slices 3 mm thick showed higher lesion loads than those with slices 5 mm thick at both entrance and follow-up examinations (median, 13.4 vs 12.8 ml and 17.5 vs 17.0 ml, respectively; p < 0.0001). The correlation between MRI and EDSS changes was significant for both MRI acquisition schemes (3 mm, r = 0.64; 5 mm, r = 0.59). The data suggest that acquisition of thinner slices does not significantly increase the sensitivity of MRI of the brain in the detection of lesion load changes in MS.
Adult↗
Detecting new lesion formation in multiple sclerosis: the relative contributions of monthly dual-echo and T1-weighted scans after triple-dose gadolinium.
In this study, we evaluated the frequency of formation of new lesions on brain magnetic resonance imaging (MRI) from patients with relapsing-remitting multiple sclerosis (MS) and defined the relative contributions of unenhanced and enhanced MRI. Every 4 weeks for 3 months, dual-echo and postcontrast T1-weighted (5 min after the injection of 0.3 mmol/kg gadolinium-DTPA) scans were obtained from 28 patients with relapsing-remitting MS. New lesions were defined as those present on dual-echo and/or postcontrast T1-weighted scans but with no corresponding MRI abnormalities on any of the preceding scans. A total of 111 newly formed lesions were detected during the follow-up on dual-echo and postcontrast T1-weighted scans (i.e., an average of 1.3 lesions per patient per month). Ninety-eight (88%) of such lesions were seen on both dual-echo and postcontrast T1-weighted scans, whilst 13 (12%) were seen only with one of the two techniques: 9 only on dual-echo and 4 only on postcontrast scans. Five of the 98 new lesions seen by both techniques were seen by postcontrast scans 1 month before their appearance on dual-echo scans. Our study suggests that both dual-echo and postcontrast T1-weighted scans are useful to detect newly formed lesions in patients with MS. This is of importance when using MRI to monitor the efficacy of treatments which may halt MS lesion formation.
Adult↗
Intraobserver and interobserver variability in measuring changes in lesion volume on serial brain MR images in multiple sclerosis.
PURPOSE: We evaluated the intraobserver and interobserver variability in measuring long-term changes in the volume of brain lesions on 5- and 3-mm-thick MR sections in patients with multiple sclerosis. METHODS: Eighteen 18 patients were scanned on two separate occasions with a mean interval of 16.4 months between the two examinations. In each session, a scan with 24 contiguous 5-mm-thick axial sections and another with 40 contiguous 3-mm-thick axial sections was acquired consecutively without moving the patient. We assessed MR lesion load by using a semiautomated local thresholding technique. RESULTS: Lesion volume was significantly higher on images with 3-mm-thick sections than on those with 5-mm-thick sections both at baseline and at follow up. Significant increases in total lesion volume were observed during the follow-up period on images obtained with both 5- and 3-mm-thick sections. The intra- and interobserver variability in measurements of changes in lesion volume was significantly higher on images with 5-mm-thick sections than on those with 3-mm-thick sections. CONCLUSION: Our data indicate that the acquisition of thinner sections increases the reliability of the assessment of changes in brain lesion load on MR images in patients with multiple sclerosis.
Adult↗
Motor evoked potentials and disability in secondary progressive multiple sclerosis.
BACKGROUND: To investigate the mechanisms underlying disability in multiple sclerosis (MS), 40 patients with the relapsing-remitting form of the disease and 13 patients with secondary progressive MS underwent multimodal evoked potential (EP), motor evoked potential (MEP), and spinal motor conduction time evaluation. Clinical disability was evaluated by the expanded disability status scale (EDSS) and functional system scales. In secondary progressive MS patients, magnetic resonance imaging (MRI) was used to obtain a semiquantitATive estimate of the total lesion load of the brain. RESULTS: Spinal motor conduction time was significantly longer in secondary progressive MS patients than controls (p < 0.001) and relapsing-remitting MS patients (p < 0.05), but did not differ between relapsing-remitting patients and controls. Spinal motor conduction times also correlated directly with EDSS scores (p < 0.001) and pyramidal functional system scores (p < 0.001). Brain lesion load (4960.3 +/- 3719.0 mm2) and the total number of lesions (67.7 +/- 37.0) in secondary progressive MS did not correlate with disability scores. For the following EPs, the frequencies of abnormalities were significantly higher in secondary progressive MS patients than relapsing-remitting patients: visual evoked potentials (p < 0.05), somatosensory evoked potentials and upper limb motor evoked potentials (p < 0.01), and brainstem auditory evoked potentials, lower limb somatosensory evoked potentials and lower limb motor evoked potentials (p < 0.001). CONCLUSIONS: These findings suggest that disability in secondary progressive MS patients is mainly due to progressive involvement of corticospinal tract in the spinal cord.
Adult↗
The effect of imprecise repositioning on lesion volume measurements in patients with multiple sclerosis.
In this study, we evaluated the effect of imprecision in patient repositioning encountered in real life on multiple sclerosis (MS) lesion volumes measured from MRIs. We also evaluated two putative methods for reducing the variability in these lesion volume measurements: first, a reduction of slice thickness (from the conventional 5 mm to 3 mm) and second, the application of a new repositioning technique based on the use of head immobilization shells. We evaluated the errors in lesion volume by scanning 10 patients a total of four times using the two slice thicknesses and two repositioning methods (conventional and using a head immobilization shell). The mean absolute percentage difference between two corresponding scans was 6.8% (range, 1.24 to 11%) using conventional slice thickness and repositioning, 4.1% (range, 0.7 to 5.56%) using conventional slice thickness and head immobilization shells, 2.6% (range, 0.8 to 6.66%) using the conventional repositioning technique and 3-mm slice thickness, and 1.4% (range, 0.2 to 6.14%) using slice thickness of 3 mm and head immobilization shells. These mean absolute differences were significantly different (p = 0.0008). Our results indicate that the effect of repositioning errors of the order of those that can be encountered in the daily life situation of clinical trials affects significantly lesion load measurements in MS and that the combined use of thinner slices and more accurate repositioning techniques can markedly improve the reproducibility of such measurements.
Adult↗
Triple dose of gadolinium-DTPA and delayed MRI in patients with benign multiple sclerosis.
OBJECTIVES: To evaluate whether a triple dose of gadolinium-DTPA (Gd-DTPA) or delayed MRI increase the number, size, and conspicuousness of enhancing lesions in patients with benign multiple sclerosis. METHODS: T1 weighted brain MRI was carried out on 20 patients with benign multiple sclerosis (expanded disability status scale < 3 with a disease duration > 10 years) in two sessions. In the first session, one scan was obtained before and two scans five to seven minutes and 20-30 minutes after the injection of 0.1 mmol/kg Gd-DTPA (standard dose). In the second session, six to 24 hours later, the same procedure was repeated with 0.3 mmol/kg Gd-DTPA (triple dose). RESULTS: Nine enhancing lesions were found in seven patients (35%) using the standard dose of Gd-DTPA. The numbers of enhancing lesions increased to 13 (P = 0.03) and the number of patients with such lesions to eight (40%) on the delayed standard dose scans. On the early triple dose scans, we found 19 enhancing lesions in 10 patients (50%). The number of enhancing lesions was significantly higher (P = 0.01) than that obtained with the early standard dose. The number of enhancing lesions was 18 and the number of "active" patients 11 (55%) on the delayed triple dose scans. The enhancing areas increased progressively from the early standard dose scans to the delayed triple dose scans. The contrast ratios of the lesions detected in early standard dose scans was lower than those of lesions present in the early (P = 0.01) and delayed (P = 0.04) triple dose scans. CONCLUSIONS: More enhancing lesions were detected in patients with benign multiple sclerosis with both delay of MRI and the use of triple dose of Gd-DTPA suggesting that the amount of inflammation in the lesions of such patients is mild and heterogeneous.
Gadolinium DTPA↗
Fragment collapsing and splitting while assembling high-resolution restriction maps.
In the process of constructing high-resolution restriction maps via greedy algorithms, a classical anomaly, known as fragment collapsing, introduces errors into the maps that impedes further map assembly. Fragment collapsing occurs when two different genomic fragments of approximately the same length and occurring in the digestion of two different overlapping clones are incorrectly identified as representative of a single genomic fragment. This introduces a single fragment of commensurate length into an incorrect position in the map. The present work describes techniques for detecting and correcting such anomalies.
Algorithms↗
Limited clinical significance of traditional and quantitative EEG in multiple sclerosis.
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Activities of Daily Living↗
Two sisters with multiple sclerosis, lamellar ichthyosis, beta thalassaemia minor and a deficiency of factor VIII.
Two of four sisters have multiple sclerosis (MS), lamellar ichthyosis, beta thalassaemia minor and a quantitative deficit of factor VIII-von Willebrand complex. The mother and the other sisters have only beta thalassaemia minor. The association of MS and a cluster of genetically determined diseases is rare. Such families could offer a new approach to the investigation of the polygenetic background of MS.
Adult↗
Serial study of neuropsychological performance and gadolinium-enhanced MRI in MS.
Many multiple sclerosis patients show cognitive decline, although no definite correlation between brain demyelination at MRI and neuropsychological performance has been found so far. We submitted a group of nine relapsing-remitting, mildly disabled patients to both serial gadolinium-DTPA enhanced MRI and neuropsychological evaluation in a follow up period of three months. Despite the great variability in acute lesions' load, no overall decline in test, performance was found. Furthermore, in selected cases whose test scores declined at follow up, no concordance with the new lesion load was found.
Adult↗