Acute-onset Restless legs syndrome in acute neurological conditions-a prospective study on patients with the Guillain-Barre syndrome and acute stroke.

OBJECTIVES: While the Restless legs syndrome (RLS) is usually recognized as a chronic condition, it has often been diagnosed among patients with acute neurological illnesses, in which limb discomfort is reported. This study was conducted to determine how many among these, actually have acute-onset RLS, and also to evaluate characteristics of this subgroup of patients with Guillain-Barre syndrome (GBS) and stroke developing acute-onset RLS. METHODS: Consecutive patients diagnosed with GBS and eligible stroke patients, admitted to our Neurology services over a 1-year period, were enrolled. They were evaluated for symptoms of RLS based on IRLSSG consensus criteria and the AIIMS RLS Questionnaire for Indian patients (ARQIP). RESULTS: Forty adults with GBS and 58 with stroke were included. A total of 10 of the 40 (25%) patients with GBS developed definite acute RLS, which was mostly monophasic. Seven (70%) of these had demyelinating type of GBS, a significant association with acute RLS (P = .024). Six of the 58 stroke patients (10%) developed definite acute-onset, often persistent RLS. Subcortical location showed significant association with increased risk of developing acute RLS (P < .001). All patients diagnosed with acute-onset RLS had an immediate and good response to dopamine agonists. CONCLUSION: This is the first study showing that acute-onset RLS is common, affecting nearly 25% of patients with GBS and 10% patients with acute stroke. Recognizing and treating it can majorly contribute toward symptom relief and early improvement in the quality of life for this population.

Role of pinch in Argon impurity transport in ohmic discharges of Aditya-U Tokamak.

We present experimental results of the trace argon impurity puffing in the ohmic plasmas of Aditya-U tokamak performed to study the argon transport behaviour. Argon line emissions in visible and Vacuum Ultra Violet (VUV) spectral ranges arising from the plasma edge and core respectively are measured simultaneously. During the experiments, space resolved brightness profile of Ar1+ line emissions at 472.69 nm (3p44s 2P3/2-3p44p 2D3/2), 473.59 nm (3p44s 4P5/2-3p44p 4P3/2), 476.49 nm (3p44s 2P1/2-3p44p 2P3/2), 480.60 nm (3p44s 4P5/2-3p44p 4P5/2) are recorded using a high resolution visible spectrometer. Also, a VUV spectrometer has been used to simultaneously observe Ar13+ line emission at 18.79 nm (2s22p 2P3/2-2s2p2 2P3/2) and Ar14+ line emission at 22.11 nm (2s2 1S0-2s2p 1P1). The diffusivity and convective velocity of Ar are obtained by comparing the measured radial emissivity profile of Ar1+ emission and the line intensity ratio of Ar13+ and Ar14+ ions, with those simulated using the impurity transport code, STRAHL. Argon diffusivities ~ 12 m2/s and ~ 0.3 m2/s have been observed in the edge (ρ > 0.85) and core region of the Aditya-U, respectively. The diffusivity values both in the edge and core region are found to be higher than the neo-classical values suggesting that the argon impurity transport is mainly anomalous in the Aditya-U tokamak. Also, an inward pinch of ~ 10 m/s mainly driven by Ware pinch is required to match the measured and simulated data. The measured peaked profile of Ar density suggests impurity accumulation in these discharges.

Impurity toroidal rotation profile measurement using upgraded high-resolution visible spectroscopic diagnostic on ADITYA-U tokamak.

A high-resolution spectroscopic diagnostic for the measurement of spatial profiles of impurity ion toroidal rotation velocities on the ADITYA-U tokamak has been upgraded to cover the complete plasma minor radius. Earlier, the coverage of diagnostics toward the plasma edge was restricted due to the placement of collection optics on the tangential port outside the vacuum vessel. The coverage of the full plasma minor radius, from 0 to 24 cm, has been achieved using the newly designed and developed collection optics that have seven lines of sight to view the tokamak plasma mounted inside a customized re-entrant view port which is installed in the shadow of the limiter inside the vacuum vessel. The upgraded diagnostic also includes a faster charged coupled device detector with a smaller pixel size for the detection of a small wavelength shift. The complete spatial profile has been measured using the Doppler shifted passive change exchange spectral line at 529.0 nm from the C5+ ion. In this article, we present the collection optics' design, installation, calibration, and results obtained using the upgraded diagnostic.

Observations of visible argon line emissions and its spatial profile from Aditya-U tokamak plasma.

The spectroscopic studies of medium and high Z impurities have been the subject of interest in fusion research due to their role in mitigating plasma disruption and reducing heat load on the plasma facing components. Line emissions from these impurities provide the rotation velocity and ion temperature measurements along with the understanding of the overall impurity behavior in plasma. In the Aditya-U tokamak, the spatially resolved Ar II line emissions have been observed using a high resolution multi-track spectroscopic diagnostic consisting of a 1 m Czerny-Turner spectrometer coupled with a charge coupled device (CCD) detector using seven lines of sight viewing plasma tangentially along the toroidal direction. The spatially resolved Ar II lines at 458.96 nm have been observed. The singly ionized Ar emission peaks at the radial location of ρ = 0.8 of the plasma having a minor radius of 25 cm. Moreover, a 0.5 m UV-visible spectrometer coupled with a CCD detector and having a line of sight passing through the plasma midplane from the radial port was used to record visible Ar survey spectra within the 670-810 nm wavelength range, and all these lines have been identified for further analysis.

Multiple antibodies targeting tumor-specific mutations redirect immune cells to inhibit tumor growth and increase survival in experimental animal models.

BACKGROUND: T cell therapy for cancer involves genetic introduction of a target-binding feature into autologous T cells, ex vivo expansion and single large bolus administration back to the patient. These reprogrammed T cells can be highly effective in killing cells, but tumor heterogeneity results in regrowth of cells that do not sufficiently express the single antigen being targeted. We describe a cell-based therapy that simultaneously targets multiple tumor-specific antigens. METHODS: High-affinity polyclonal rabbit antibodies were generated against nine different surface-related tumor-specific mutations on B16F10 cells. Unsorted splenic effector cells from syngeneic mice were incubated with a cocktail of the nine anti-B16F10 antibodies. These 'armed' effector cells were used to treat mice previously inoculated with B16F10 melanoma cells. RESULTS: The cocktail of nine antibodies resulted in dense homogeneous binding to histological sections of B16F10 cells. Five treatments with the armed effector cells and PD1 inhibition inhibited tumor growth and improved survival. Shortening the interval of the five treatments from every three days to every day increased survival. Arming effector cells with the four antibodies showing best binding to B16F10 cells even further increased survival. CONCLUSIONS: This study demonstrates that ex vivo arming a mixed population of immune effector cells with antibodies targeting multiple tumor-specific mutated proteins in conjunction with PD1 inhibition delayed tumor growth and prolonged survival in mice inoculated with an aggressive melanoma. A remarkably low total antibody dose of less than 5 µg was sufficient to accomplish tumor inhibition. Scaling up to clinical level may be feasible.

Clinical spectrum of Hallervorden-Spatz syndrome in India.

Hallervorden-Spatz syndrome is a rare autosomal recessive disorder that involves progressive extrapyramidal manifestations. Classical and atypical clinical presentations are known. Clinical details of patients admitted to the neurology ward or attending the movement disorder clinic of the All India Institute of Medical Sciences between January 2001 and July 2007 were reviewed. Sixteen patients (9 males and 7 females) were included in the study (median age 14 years; range 6-25). The most common clinical presentation was limb or cranial onset progressive dystonia. The patients with early onset had more frequent truncal and axial dystonia, including retrocollis, oromandibular-facial dystonia and chorea, dysarthria, pyramidal signs, gait disturbance, cognitive impairment, delay in milestones, retinitis pigmentosa, optic atrophy, oculomotor abnormalities, positive family history and acanthocytosis. Although rare, cerebellar ataxia, behavioural abnormalities, parkinsonism and apraxia of eyelid opening were exclusively seen in late onset patients. The present study highlights the heterogeneity of this disease entity and also describes certain unusual clinical features.

Annual risk of tuberculosis infection among tribal population of central India.

OBJECTIVE: To estimate the annual risk of tuberculosis infection (ARTI) among tribal children of Madhya Pradesh, central India. METHODS: Community-based, cross-sectional tuberculin survey among children aged 1-9 years in the tribal population of Madhya Pradesh. Multistage stratified cluster sampling was used to select a representative random sample of villages predominated by tribal population from selected districts. A total of 4802 children were tuberculin-tested with 1TU of PPD RT 23 and the reaction sizes read after 72 h. RESULTS: A total of 3062 (64%) children had no BCG scar. The frequency distribution of children by reaction sizes indicated a fair mode at 18 mm in the right hand side of the distribution. By mirror-image technique, the prevalence of infection among children with no recognizable BCG scar was estimated as 6.8% (95% CI: 4.8-8.9%). The ARTI was computed as 1.3% (0.9-1.7%). The corresponding figures for children irrespective of scar status were 7.1% (95% CI: 5.5-8.8%) and 1.3% (1.0-1.7%) respectively. CONCLUSIONS: The risk of tuberculosis infection in tribal population of Madhya Pradesh, central India is not different from other areas of the country. There is, however, a need to further intensify tuberculosis control measures on a sustained and long-term basis.

Functional mapping in PD and PSP for sustained phonation and phoneme tasks.

AIM: To elucidate the central basis of articulatory speech disorders in Parkinsonian syndromes using functional magnetic resonance imaging (fMRI). METHODS: Twenty-two patients with Parkinson's disease (PD) and 18 with progressive supranuclear palsy (PSP) were clinically evaluated for speech dysfunction. Functional magnetic resonance imaging (fMRI) was carried out in these patients using sustained phonation and phoneme tasks. Individual and group analysis using SPM2 was done for eight patients with PD, 7 with PSP and 6 healthy controls. SETTING: Tertiary Medical Teaching Institute. RESULTS: For sustained phonation paradigm, superior temporal gyrus area was activated in PD patients, and occipital cortex in PSP subjects in comparison to controls. For phoneme paradigm, the patients with PD recruit lingual gyrus obviating the need for more efforts for the task. Also wider areas as well as more clusters were activated in PD patients compared to controls. Lingual gyrus was found to be strongly activated in PSP patients. Reduced activation of the primary areas with recruitment of remote areas was another prominent finding in PSP. Due to excessive motion (>1.5 mm, >1 degrees ) in all the MSA patients, they could not be considered for analysis. CONCLUSION: The failure of the executive fronto-striatal network would lead to increased activation of other areas in PD, but in PSP, there is a widespread cortical dysfunction.

Tuberculous infection in Saharia, a primitive tribal community of Central India.

A cross-sectional tuberculin survey was carried out to estimate the prevalence of tuberculous infection and the annual risk of tuberculosis infection (ARTI) among children of Saharia, a primitive ethnic group in Madhya Pradesh, Central India. A total of 1341 children aged 1-9 years were subjected to tuberculin testing with 1 TU of PPD RT 23 and the reaction sizes were read after 72 h. The proportion of BCG scar-positive children was 34.6%. The frequency distribution of children by reaction sizes indicated a clear-cut anti-mode at 11 mm and a mode at 18 mm at the right-hand side of the distribution. The prevalence of infection among children irrespective of BCG scar was estimated as 20.4% (95% CI 18.2-22.5%) and the ARTI was 3.9% (95% CI 3.5-4.3%). The corresponding figures were 21.1% (95% CI 18.3-23.8%) and 3.9% (95% CI 3.4-4.5%) among BCG scar-negative children and 19.0% (95% CI 15.4-22.5%) and 4.0% (95% CI 3.2-4.8%) among BCG scar-positive children. The findings of the present study show a high prevalence of tuberculous infection and high ARTI in this primitive ethnic group. There is an urgent need to further intensify tuberculosis control measures on a sustained and long-term basis in this area.

Clinical speech impairment in Parkinson's disease, progressive supranuclear palsy, and multiple system atrophy.

CONTEXT: Speech abnormalities are common to the three Parkinsonian syndromes, namely Parkinson's disease (PD), progressive supranuclear palsy (PSP) and multiple system atrophy (MSA), the nature and severity of which is of clinical interest and diagnostic value. AIM: To evaluate the clinical pattern of speech impairment in patients with PD, PSP and MSA and to identify significant differences on quantitative speech parameters when compared to controls. DESIGN AND SETTING: Cross-sectional study conducted in a tertiary medical teaching institute. MATERIALS AND METHODS: Twenty-two patients with PD, 18 patients with PSP and 20 patients with MSA and 10 age-matched healthy controls were recruited over a period of 1.5 years. The patients were clinically evaluated for the presence and characteristics of dysarthria. This was followed by quantitative assessment of three parameters: maximum phonation time (MPT), semantic fluency and reading speed. The outcome measures were compared between the patient groups and with controls. RESULTS: Patients with PD had hypophonic monotonous speech with occasional rushes of speech while patients with MSA and PSP had mixed dysarthria with ataxic and spastic elements respectively. All quantitative parameters were affected when compared to controls (P values<0.001, 0.012 and 0.008 respectively). Maximum phonation time was significantly less in PSP when compared to MSA and PD (P=0.015). Reading speed also showed a similar trend which was not statistically significant. Semantic fluency was comparable in all three groups. CONCLUSION: Dysarthria in PD, PSP and MSA have many overlapping but certain distinctive features as well which could serve as a diagnostic clue. Patients with PSP had profound speech impairment probably indicative of the more severe frontostriatial pathology.

Plasma rotation measurement using UV and visible spectroscopy on Aditya-U tokamak.

A high resolution spectroscopic diagnostic for the measurement of the spatial profile of toroidal rotation velocity (vt) and temperature (Ti) of carbon ions has been developed and implemented on the Aditya-U tokamak. The diagnostic consists of a high resolution 1 m (f/8.7) spectrometer having an 1800 grooves/mm grating coupled with a charged couple device. The setup allows measurements from 5 toroidal lines-of-sights passing through different minor radii in the horizontal mid-plane of the Aditya-U tokamak. The carbon line emissions at 529 nm in visible and 229.6 and 227.09 nm in the ultra violet spectral range are recorded using the setup. Initial results show that typical Aditya-U plasmas have a maximum carbon ion temperature (Ti) of ∼120 eV and a rotation velocity (vt) of ∼-14 km/s in the counter plasma-current direction.

Design of tangential x-ray crystal spectrometer for Aditya-U tokamak.

A tangential soft x-ray crystal spectrometer has been designed to measure the x-ray spectrum of He-like argon for the Aditya-U tokamak plasma. The system enables to measure electron temperature using the intensity ratio of the resonance line to the satellite line. For this purpose, an x-ray spectral line at 3.9494 Å from He-like argon, Ar16+, is considered. The spectrometer consists of a cylindrically bent silicon (111) crystal and a CCD detector to measure the resonance spectral line and its satellite lines in the wavelength region of 3.94-4.0 Å, viewing the plasma tangentially at an angle of 26° with respect to the toroidal direction in the magnetic axis. Considering Aditya-U tokamak plasma parameters and its geometrical constraints, plasma to crystal and crystal to detector distances have been kept at 1.47 m and 0.5 m, respectively, to detect a sufficient signal. The engineering design has been optimized after adequately addressing the issues related to port geometry and machine accessibility. Details on the design of the crystal spectrometer are presented in this paper.

Hyperacute thrombolysis with IV rtPA of acute ischemic stroke: efficacy and safety profile of 54 patients at a tertiary referral center in a developing country.

BACKGROUND: Given the constraints of resources, thrombolysis for acute ischemic stroke (AIS) is under evaluation in developing countries. Prothrombin time (PT), platelet count and activated partial thromboplastin time (aPTT) may not be feasible within the time window. AIM: To evaluate the safety and efficacy of thrombolysis in selected patients without the coagulation profile. DESIGN: Open, nonrandomized, observational study. MATERIALS AND METHODS: Fifty-four stroke patients were classified using TOAST criteria (large artery atherosclerotic = 13; cardioembolic = 12; small vessel occlusion = 22; other determined etiology =three; undetermined etiology = four). The mean time to reach emergency was 2.4h (1.15-3.4), the mean door to CT, 24 min (10-47) and the door to recombinant tissue plasminogen activator (r-tPA) injection, 26.8 min (25-67). The NIHSS scores ranged from 11 to 22 (mean = 15.5 +/- 2.7). Patients with history of liver or renal disease or those on anticoagulants were excluded. The PT, aPTT and platelet count were not done. Recombinant tissue plasminogen activator was administered at a dosage of 0.9 mg/Kg. RESULTS: Thirty-five patients (65%) significantly improved on NIHSS at 48 h (> or =4 points) (mean change = 10; range= 4-17). At one month, 43 (79%) improved on Barthel Index (mean change = 45%). One each developed small frontal lobe hemorrhage and recurrent stroke; one died of aspiration; and eight showed no improvement. CONCLUSIONS: Hyperacute thrombolysis was found useful and safe in selected patients with AIS even without the coagulation studies.

Biochemical control and toxicity for favorable- and intermediate-risk patients using real-time intraoperative inverse optimization prostate seed implant: Less is more!

PURPOSE: To report the biochemical control rate and clinical outcomes with real-time inverse planning (inverse optimization prostate seed implant [IO-PSI]) for favorable-risk (FR) and intermediate-risk (IR) prostate adenocarcinoma in a community practice setting. This analysis is an extended followup of our initial report, with favorable early biochemical control rate (biochemical nonevidence of disease) of 97% at 4 years. METHODS AND MATERIALS: Three hundred fifty-seven evaluable patients with FR and IR prostate cancer underwent real-time IO-PSI (iodine-125/145 Gy or palladium-103/120 Gy) between 2001 and 2013. RESULTS: With a median followup of 54 months (range, 24-110 months), the absolute biochemical failure free survival of disease was 96%. The 8-year actuarial probability of prostate-specific antigen failure-free survival for FR and IR cohorts was 92.4% and 87%, respectively. Late genitourinary and gastrointestinal toxicity remained low. Late Grade 2 and Grade 3 genitourinary toxicity was 19% and 1%, respectively. Late Grade 2 and 3 rectal bleeding rates were 1% and 0%, respectively. No difference in biochemical control was observed with preimplant short course androgen deprivation or between Gleason score 3 + 4 vs. 4 + 3 patients. No dosimetric parameter was predictive of biochemical failure. Patients with FR had a significantly decreased risk of failure (hazard ratio = 0.26; 95% confidence interval = 0.09-0.78; p = 0.02) compared with those with IR. Patients with a prostate-specific antigen nadir >0.4 ng/mL had an increased risk of failure (hazard ratio = 1.37; 95% confidence interval = 1.27-1.47; p < 0.0001). CONCLUSIONS: Our initial biochemical and clinical outcomes using real-time IO-PSI persisted with extended followup and support our original hypothesis for use of a reduced number of sources, needles, and total activity, suggesting that with IO, less is more.

Androgen receptor-related diseases: what do we know?

The androgen receptor (AR) and the androgen-AR signaling pathway play a significant role in male sexual differentiation and the development and function of male reproductive and non-reproductive organs. Because of AR's widely varied and important roles, its abnormalities have been identified in various diseases such as androgen insensitivity syndrome, spinal bulbar muscular atrophy, benign prostatic hyperplasia, and prostate cancer. This review provides an overview of the function of androgens and androgen-AR mediated diseases. In addition, the diseases delineated above are discussed with respect to their association with mutations and other post-transcriptional modifications in the AR. Finally, we present an introduction to the potential therapeutic application of most recent pharmaceuticals including miRNAs in prostate cancer that specifically target the transactivation function of the AR at post-transcriptional stages.

Rapid kidney changes resulting from glycosphingolipid depletion by treatment with a glucosyltransferase inhibitor.

The ceramide analog, D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol, inhibits the glucosylation of ceramide and thus, by virtue of the normal catabolism of the higher glucosphingolipids, leads to a general depletion of cellular glucolipids. In a previous study with chronic administration of this inhibitor in mice, it was found that the kidneys and liver, particularly the former, grew more poorly than the organs of control mice. This study shows that the inhibitor produces rapid decreases in glucolipid concentration in kidney which are maintained for at least 5 days without noticeable harm. The changes were enhanced by inclusion of L-cycloserine in the injection scheme. Cycloserine blocks ketosphinganine synthase and thus slows the synthesis of all sphingolipids. However, sphingomyelin levels did not drop significantly in this study. The glucosyltransferase inhibitor also produced a small decrease in kidney beta-D-glucuronidase and distinct increases in the levels of glucocerebrosidase, galactocerebrosidase and sphingomyelinase. It also produced a small but distinct decrease in the level of glucosyltransferase, after a delay of a few hours, possibly because the inhibitor was metabolized to a covalently inactivating product. Comparison with kidney, liver and brain showed that the kidney was more sensitive to the action of the morpholino inhibitor.

Widespread electromyographic abnormalities in patients with monomelic amyotrophy: a detailed EMG study.

OBJECTIVE: To evaluate subclinical electromyographic changes in unaffected muscles of the patients with monomelic amyotrophy (MMA). PATIENTS AND METHODS: 35 patients of MMA with single limb atrophy (30 patients with upper limb involvement and 5 patients with lower limb involvement) were studied at All India Institute of Medical Sciences, New Dellhi, from September 2000 to September 2002. All the patients were evaluated clinically, by detailed three limb electromyography (EMG) and by MRI scan of the spine to rule out other disorders. RESULTS: The mean age of 35 male patients was 24.17 (+/-6.8) years and the mean duration of illness was 3.64 (+/-2.7) years. Patients with upper limb involvement had segmental pattern of atrophy, predominantly distal or proximal. EMG revealed evidence of subclinical diffuse chronic reinnervative changes. All the patients (100%) had bilateral chronic reinnervative changes and 50% had chronic reinnervative changes in three limbs. CONCLUSIONS: Patients with clinically single limb MMA were found to have evidence of widespread chronic reinnervative changes on EMG.

Quantitative thermal sensory testing in patients with monomelic amyotrophy.

BACKGROUND: Quantitative thermal sensory testing (QST) is a non-invasive method to assess somatic small fibre dysfunction, which is not evaluated with routine nerve conduction studies (NCS). Monomelic amyotrophy (MMA), is a pure motor disorder with no sensory abnormalities on routine NCS, and has not been evaluated using QST. AIMS AND OBJECTIVE: Present study aimed to evaluate somatic small fibre involvement in MMA patients. Forty patients with MMA with no sensory abnormalities or routine NCS were evaluated using QST for thresholds of cold sensation (CS), warm sensation (WS), cold pain (CP) and warm pain (WP), using method of limits. These were compared with 40 age-matched controls. RESULTS: No abnormalities in thresholds for CS, WS, CP and WP were found in MMA group as compared to controls. CONCLUSION: QST thus failed to demonstrate any abnormality. Hence we conclude that MMA is a pure motor disorder, with no involvement of somatic small sensory fibres (A delta and C).

Improved inhibitors of glucosylceramide synthase.

An inhibitor of glucosylceramide (GlcCer) synthase, 1-phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP), has been reported to deplete cells and mice of their glucosphingolipids. This inhibitor has proved useful for the elucidation of the many functions of this lipid family [reviewed by Radin, N.S. & Inokuchi, J. (1991) Trends Glycosci. Glycotechnol. 3, 200-213]. In the present study, we have synthesized homologs of PDMP having different acyl chains (C6-C18) and compared their effectiveness for the inhibition of GlcCer synthase in vitro and their inhibition of GlcCer, protein, and DNA synthesis in cultured MDCK (Madin-Darby canine kidney) cells. Using MDCK homogenates and mouse brain and liver microsomes, we found that the C6 compound was relatively inactive and that the longer chain compounds did not differ much in inhibitory power. However, the use of intact MDCK cells showed that the longer chain homologs were much more effective in inhibiting GlcCer synthesis, cell growth, and incorporation of [3H]thymidine. Tests with two radioactive homologs showed that the inhibitor with a longer acyl chain was taken up much more effectively by MDCK cells and that this difference explains the much greater effectiveness of this homolog in intact cells. The inhibitors were effective when solubilized either with a nonionic detergent or with bovine serum albumin. The extent of decrease in DNA synthesis was not directly proportional to the decrease in cellular glucosylceramide, possibly because only a low level of the glycolipid is needed for DNA synthesis.