Uncontrollable movements in patient with diabetes mellitus.
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Brain↗
Biomedical subjects
Sanjay Kalra
Publications and source records attributed to Sanjay Kalra.
Rapid improvement in cortical neuronal integrity in amyotrophic lateral sclerosis detected by proton magnetic resonance spectroscopic imaging.
Riluzole prolongs survival in amyotrophic lateral sclerosis. The temporal and spatial profile of its effect on the brain is unknown. We used proton magnetic resonance spectroscopic imaging to evaluate the neuronal response to 1 day of riluzole treatment in motor and non-motor regions of the brain. In 10 patients the N-acetylaspartate/total creatine (NAA/Cr) ratio increased in the precentral gyrus and supplementary motor area, but not in the post-central gyrus or parietal lobe. Improvement in cortical neuronal metabolic function in the motor cortex occurs early with riluzole treatment.
Aged↗
Detection of cerebral degeneration in amyotrophic lateral sclerosis using high-field magnetic resonance spectroscopy.
BACKGROUND: Clinical assessment is insensitive to the degree of cerebral involvement in amyotrophic lateral sclerosis (ALS). Regional brain concentrations N-acetylaspartylglutamate (NAA) plus myo-inositol (Ins), as measured by magnetic resonance spectroscopy, are respectively decreased and increased, suggesting that these compounds may provide a biomarker of the degree of cerebral involvement in ALS. OBJECTIVE: To test the hypothesis that the NAA/Ins ratio may provide an index of cerebral involvement in patients with ALS. DESIGN: High-field (3.0-T) magnetic resonance spectroscopy was performed to determine the NAA/creatine plus phosphocreatine (NAA/Cr), NAA/choline (NAA/Cho), Ins/Cr, and NAA/Ins ratios in the motor cortex. PARTICIPANTS: Seventeen patients with ALS and 15 healthy control subjects were studied. RESULTS: In patients with ALS, the greatest abnormality was a 22% decrease in NAA/Ins (71% sensitivity and 93% specificity, P = .001); Ins/Cr was increased 18% (88% sensitivity and 53% specificity, P = .04), NAA/Cr was decreased 10% (88% sensitivity and 47% specificity, P = .04), and NAA/Cho was decreased 14% (53% sensitivity and 87% specificity, P = .047). Correlation of the ALS Functional Rating Scale with NAA/Ins approached statistical significance (R = 0.43, P = .07). CONCLUSION: The NAA/Ins ratio may provide a meaningful biomarker in ALS given its optimal sensitivity and specificity profile.
Adult↗
Proton spectral editing for discrimination of lactate and threonine 1.31 ppm resonances in human brain in vivo.
A single-voxel proton NMR J-difference editing method for discriminating between the 1.31 ppm resonances of lactate (Lac) and threonine (Thr) in human brain in vivo at 3 T is reported. One double-band and two triple-band Gaussian 180 degrees RF pulses, all with a bandwidth of 15 Hz, were employed within an adiabatic-refocused double-echo localization sequence to induce the target signals of Lac and Thr and simultaneously acquire a creatine singlet in each subscan. The optimum echo time and the editing efficiency were obtained by numerical analysis of the filtering performance. The Lac and Thr signals were extracted, without lipid contamination, from three subspectra. Using the calculated yields, the concentrations of Lac and Thr in the human occipital cortex were estimated to be 0.47+/-0.07 and 0.56+/-0.06 mM (mean+/-SD, N=7), respectively, with reference to Cr at 8 mM.
Algorithms↗
T2 measurement and quantification of glutamate in human brain in vivo.
The proton NMR transverse relaxation time T(2) of glutamate (Glu) in human brain was measured by means of spectrally selective refocusing at 3.0 T in vivo. An 81.4-ms-long dual-band Gaussian 180 degrees RF pulse, designed for refocusing at 2.35 and 3.03 ppm, was employed within point-resolved spectroscopy (PRESS) to generate the Glu C4-proton target multiplet and the total creatine (tCr) singlet. Six optimal echo times (TEs) between 128 and 380 ms were selected from numerical analysis of the filtering performance for effective detection of the Glu signal with minimal contamination from glutamine (Gln), N-acetylaspartate (NAA), and glutathione (GSH). The magnetization of Glu and tCr was extracted from spectral fitting of experimental and calculated spectra. Apparent T(2) values of Glu and tCr were estimated as 201 +/- 18 and 164 +/- 12 ms for the medial prefrontal (PF) cortex, and 198 +/- 22 and 169 +/- 15 ms (mean +/- SD, N = 5) for the left frontal (LF) cortex, respectively. With water segmentation data, the magnetization values of Glu and tCr of the two adjacent voxels, calculated from the T(2) values and spectra following the thermal equilibrium magnetization, were combined to give the Glu and tCr concentrations as 10.37 +/- 1.06 and 8.87 +/- 0.56 mM for gray matter (GM), and 5.06 +/- 0.57 and 5.16 +/- 0.45 mM (mean +/- SD, N = 5) for white matter (WM), respectively.
Adult↗
Magnetic resonance spectroscopy for monitoring neuronal integrity in amyotrophic lateral sclerosis.
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Amyotrophic Lateral Sclerosis↗
Unilateral atrophy of fungiform papillae associated with lingual nerve injury.
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Adult↗
Hot tub lung: presenting features and clinical course of 21 patients.
BACKGROUND: Hot tub lung is an emerging lung disorder associated with exposure to Mycobacterium avium complex organisms contaminating hot tub water. OBJECTIVES: To define the clinical characteristics and outcome of patients with hot tub lung. METHODS: Retrospective review of 21 patients diagnosed with hot tub lung at a tertiary medical center over a 7-year period. RESULTS: The mean (+/-sd) age at presentation was 46 (+/- 15) years; 9 patients were men (43%). All patients described ongoing exposure to hot tubs. The most common referral diagnoses were sarcoidosis, bronchitis, and asthma. Dyspnea and cough were present in all patients, hypoxemia was noted in 10 patients (48%). High-resolution computed tomography of the chest had been performed in 20 patients and demonstrated diffuse centrilobular nodules and/or ground-glass opacities in all patients. M. avium complex was isolated from the hot tub water, respiratory secretions and/or lung tissue in all patients. Bronchoscopic or surgical lung biopsy was obtained in 18 patients and demonstrated bronchiolocentric granulomatous inflammation. With avoidance of exposure, clinical and radiologic improvement was observed in all patients. Additionally, 13 patients (62%) received corticosteroid therapy, 1 (5%) antimycobacterial therapy, 2 (10%) received both, and 5 patients (24%) received no pharmacologic therapy. CONCLUSIONS: Hot tub lung likely represents hypersensitivity pneumonitis due to inhalational exposure to M. avium complex. Antimycobacterial therapy does not appear to be required in the management of this disease. Although corticosteroids may be helpful in the treatment of severely affected patients, others can be managed by avoidance of additional exposure alone.
Adrenal Cortex Hormones↗
A prospective, randomized, placebo-controlled evaluation of corticoneuronal response to intrathecal BDNF therapy in ALS using magnetic resonance spectroscopy: feasibility and results.
During the multicenter, phase III trial of intrathecal BDNF in ALS, we evaluated the neuronal marker N-acetylaspartate (NAA) as a surrogate marker of therapeutic efficacy using proton magnetic resonance spectroscopic imaging (MRSI) in a prospective and blinded manner. Selected subjects tolerated the study well without pump malfunction. The NAA to creatine (Cr) intensity ratio (NAA/Cr) was measured in the precentral and postcentral gyri, the superior parietal lobule, the supplementary motor area, and the premotor cortex. After 4.5+/-0.6 weeks treatment, NAA/Cr did not change significantly in any of the regions in the BDNF-treated group (n=5) compared to the placebo group (n=6). The lack of change in NAA correlated with the lack of clinical efficacy and supports the validity of NAA/Cr as a surrogate in this setting. MRSI is a feasible and safe method to evaluate intrathecal therapies in ALS.
Adult↗
Neuroimaging in amyotrophic lateral sclerosis.
Several neuroimaging modalities have been used with varying success to aid the clinical process of establishing the diagnosis of amyotrophic lateral sclerosis (ALS). By demonstrating evidence of occult upper motor neuron degeneration in vivo, a speedier and more definitive diagnosis in suspected cases could lead to earlier treatment and earlier enrollment in clinical trials. Findings compatible with ALS on routine MRI are not consistently found and are non-specific. Thus, routine anatomic imaging is useful in ruling out diseases that mimic ALS, but not in classification of new cases. Functional imaging techniques, such as PET and fMRI, have provided fascinating insights into the cortical functional reorganization that accompanies muscular weakness. PET and SPECT have revealed involvement of regions of the brain beyond the motor cortex, something not well appreciated by pathological examination. Of great need is a surrogate marker of therapeutic efficacy to make drug evaluation more efficient; neuroimaging, and magnetic resonance spectroscopy in particular, holds great promise in this regard in addition to helping us better understand the of neurodegeneration.
Amyotrophic Lateral Sclerosis↗
Etanercept for the treatment of stage II and III progressive pulmonary sarcoidosis.
BACKGROUND: Tumor necrosis factor (TNF)-alpha is produced by macrophages and other cells, and is believed to participate in granulomatous inflammation. Targeted antagonism of TNF-alpha has been proposed as a novel treatment strategy for sarcoidosis. Etanercept is a dimeric fusion protein that binds specifically to TNF-alpha, rendering it biologically inactive. OBJECTIVE: To assess whether etanercept has potential efficacy in the treatment of progressive pulmonary sarcoidosis. DESIGN: Prospective, open-label, phase-2 treatment trial. SETTING: Mayo Clinic, Rochester, MN. PATIENTS: Stage II or III progressive pulmonary sarcoidosis. INTERVENTION: Etanercept, 25 mg subcutaneously twice weekly. MEASUREMENTS: Pulmonary function, chest radiographs, dyspnea, and TNF-alpha levels in serum and BAL fluid. RESULTS: The study was terminated after the enrollment of 17 patients due to an early-stop clause of the pretrial study design related to excessive treatment failures. Neither absolute levels of TNF-alpha nor TNF-alpha activity in the serum, BAL fluid, or alveolar macrophages were able to predict which patients would respond to etanercept. CONCLUSIONS: In patients with progressive stage II or III pulmonary sarcoidosis, etanercept was frequently associated with early or late treatment failure. These data would not support the design of a large multicenter randomized trial comparing etanercept with conventional corticosteroid therapy.
Anti-Inflammatory Agents, Non-Steroidal↗
56-year-old man with progressive shortness of breath.
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Chronic Disease↗
Interferon gamma-1b therapy for advanced idiopathic pulmonary fibrosis.
OBJECTIVE: To report on observations made in a group of patients with idiopathic pulmonary fibrosis/usual interstitial pneumonia (IPF/UIP) who were treated with interferon gamma-1b. PATIENTS AND METHODS: We reviewed the clinical records, radiological studies, and pulmonary function data of all patients treated with interferon gamma-1b between January 2000 and March 2002 at the Mayo Clinic in Rochester, Minn. RESULTS: Twenty-one patients (mean age, 68 years; range, 52-80 years) were treated with interferon gamma-1b for a mean duration of 82 months (range, 3-21 months). All patients had been diagnosed previously as having IPF/UIP based on clinical, pulmonary function, and chest high-resolution computed tomographic scan criteria; 12 patients had also undergone video-assisted thoracoscopic surgical lung biopsy. Baseline pulmonary function data (mean +/- SEM percent predicted) were as follows: total lung capacity, 57.3 +/- 2.5; vital capacity, 55.0 +/- 3.3; diffusing capacity of lung for carbon monoxide, 39.7 +/- 2.8; and forced expiratory volume in 1 second, 58.1 +/- 3.6. Only 1 patient showed symptomatic and functional improvement, and 7 discontinued treatment because of a perceived lack of benefit. Eleven patients (52%) died after a mean of 6.4 months of treatment, and follow-up pulmonary function data suggested continued worsening in all but 1 patient. CONCLUSION: These observations do not support the use of interferon gamma-lb therapy for patients with advanced IPF/UIP.
Aged↗
Gabapentin therapy for amyotrophic lateral sclerosis: lack of improvement in neuronal integrity shown by MR spectroscopy.
BACKGROUND AND PURPOSE: Proton MR spectroscopy has revealed impaired neuronal integrity in the motor cortex of patients with amyotrophic lateral sclerosis (ALS). We hypothesized that the N-acetylaspartate (NAA)-creatine (Cr) ratios in the motor cortex and adjacent brain could reflect the therapeutic effectiveness of gabapentin (GBP) treatment in ALS. METHODS: Eight patients with ALS underwent MR spectroscopy before and 26.5 days +/- 8.8 after starting GBP. In 10 patients with ALS who were not treated with GBP, paired spectra were obtained 21.4 days +/- 7.2 apart. Fourteen healthy subjects underwent a single MR spectroscopic examination. The NAA/Cr ratio was measured in the precentral gyrus, the postcentral gyrus, the superior parietal lobule, the supplementary motor area, and the premotor cortex. RESULTS: The NAA/Cr ratio was decreased in the precentral and postcentral gyri of patients with ALS compared with healthy controls. In those with ALS, the change in the NAA/Cr ratio was not different between treated patients and untreated patients in any of the regions studied. CONCLUSION: No improvement in neuronal integrity was detected in motor and nonmotor cerebral regions after GBP treatment. This result agrees with that of prior investigations showing the equivocal clinical effectiveness of GBP for ALS and supports the validity of the NAA/Cr ratio as a surrogate of therapeutic effectiveness.
Acetates↗
Hypersensitivity pneumonitis associated with Mycobacterium avium complex and hot tub use.
Many diseases, mainly infectious and inhalational, have been associated with the use of hot tubs. "Hot tub lung" is a recently described disease entity associated with Mycobacterium avium complex (MAC) and is thought to be either an infection or a hypersensitivity pneumonitis. We describe 2 patients with progressively worsening respiratory symptoms and pulmonary function, along with diffuse radiographic changes consisting primarily of ground-glass opacities. Treatment with corticosteroids, based on lung biopsies suggesting sarcoidosis in 1 patient and eosinophilic bronchiolitis in the other, resulted in little improvement with both patients experiencing respiratory failure. Both patients continued regular and continued hot tub use despite ongoing respiratory difficulties, and MAC was identified in the hot tub water and/or lung tissue from each patient. Discontinuation of hot tub use, without antimycobacterial therapy, led to prompt improvement in symptoms, pulmonary function, and radiographic abnormalities, strongly supporting a diagnosis of hypersensitivity pneumonitis. Hypersensitivity to MAC, rather than an infection, is the likely underlying mechanism in these 2 cases of hot tub lung.
Alveolitis, Extrinsic Allergic↗