Randomized Assessment of the Safety and Efficacy of Intra-Arterial Infusion of Autologous Stem Cells in Subacute Ischemic Stroke.

BACKGROUND AND PURPOSE: Stroke is a debilitating illness for which treatment window is limited. Most patients present to the healthcare facility beyond that window. Autologous stem cells have shown some promise for this group of patients. This study was performed to evaluate the safety and the efficacy of intra-arterial infusion of bone marrow-derived mononuclear cells in patients with middle cerebral artery ischemic stroke. MATERIALS AND METHODS: A prospective, randomized, open-label, blinded-end point study was performed from July 2015 to June 2016. Of 229 patients with acute stroke who presented to the hospital during this period, 20 patients who satisfied the inclusion/exclusion criteria were included and randomized into the control and intervention groups. Intra-arterial stem cell infusion into the ipsilateral MCA was performed in the patients in the intervention group at 8-15 days post-stroke ictus. Final analysis at 6 months was performed for primary (safety) and secondary outcomes (efficacy). RESULTS: When we compared the primary end point of the study, no procedure-related mortality, complication, new infarct, or symptomatic intracranial hemorrhage was seen in the intervention group. When we compared the secondary end point of good clinical outcome, 8 (80%) patients in the intervention group showed good clinical outcome (modified Rankin Scale score < 2) with 4 (40%) patients in the control group achieving this (95% confidence interval for good outcome in patients with stem cell infusion, 49.03-94.3, and without stem cell infusion, 16.82-68.73; P = .068). CONCLUSIONS: Intra-arterial infusion of stem cells can be carried out safely in the subacute stage of ischemic stroke. Improved clinical outcomes were observed with intra-arterial stem cell therapy; however, studies with larger cohorts are needed to validate the results.

Lipoprotein Particles in Adolescents and Young Women With PCOS Provide Insights Into Their Cardiovascular Risk.

CONTEXT: Adult women with polycystic ovarian syndrome (PCOS) have an increased risk for cardiovascular disease, but the evidence for this is controversial in adolescents and young women with PCOS. Measurement of low-density lipoprotein (LDL) particle number, measured by nuclear magnetic resonance spectroscopy is a novel technology to assess cardiovascular risk. OBJECTIVE: The objective of the study was to evaluate lipoprotein particle number and size in young women with PCOS and its relationship with insulin resistance and hyperandrogenism. DESIGN: This was a cross-sectional case control study. SETTING: The study was conducted at a clinical research center. PARTICIPANTS: Women with PCOS (n = 35) and normal controls (n = 20) participated in the study. INTERVENTIONS: Blood samples and anthropometric measures were obtained. MAIN OUTCOME MEASURES: LDL particle size and number were measured using nuclear magnetic resonance spectroscopy. A secondary outcome was to investigate the correlation of LDL particle number with high-sensitivity C-reactive protein, waist to hip ratio, hyperandrogenism, insulin resistance, and adiponectin. RESULTS: Women with PCOS had higher LDL particle number when compared with healthy controls (935 ± 412 vs 735 ± 264, P = .032); LDL particle number correlated strongly with high-sensitivity C-reactive protein (r = 0.37, P = .006) and waist-to-hip (r = 0.57, P = .0003). The higher LDL particle number was driven mainly due to differences in the small LDL particle number (sLDLp), with PCOS patients having more sLDLp (348 ± 305 vs 178 ± 195, P = .015). The sLDLp correlated with the Matsuda index (r = -0.51, P = .0001), homeostasis model assessment index of insulin resistance (r = 0.41, P = .002), and adiponectin (r = -0.46, P = .0004) but not with T. CONCLUSION: Adolescent and young women with PCOS have an atherogenic lipoprotein profile suggestive of increased cardiovascular risk that appears to be driven by the degree of visceral adiposity and insulin resistance.

Idiopathic CD4 lymphocytopenia presenting as refractory cryptococcal meningitis.

Idiopathic CD4 T-lymphocytopenia (ICL) is a syndrome characterized by depletion of CD4 T-cells without evidence of human immunodeficiency virus (HIV) infection. There are a few reported cases of ICL associated with different diseases and clinical conditions, most commonly the opportunistic infections like Tuberculosis, fungal and parasitic diseases which are also seen in HIV-positive patients. We report a case without risk factors or laboratory evidence of HIV infection who presented with refractory cryptococcal meningitis and was found to have ICL.

Implant for augmentation of cerebral blood flow trial 1: a pilot study evaluating the safety and effectiveness of the Ischaemic Stroke System for treatment of acute ischaemic stroke.

INTRODUCTION: In rat stroke models, sphenopalatine ganglion stimulation up to 24 h after stroke onset augments cerebral blood flow, reduces infarct volume and improves neurological deficits. The ischaemic stroke system 500 has been designed to stimulate the sphenopalatine ganglion in humans. OBJECTIVES: (1) To determine the safety and tolerability of the ischaemic stroke system 500 in acute ischaemic stroke within 24 h of stroke onset. (2) To determine the effectiveness of ischaemic stroke system 500 in acute ischaemic stroke treatment. DESIGN/METHODS: Implant for augmentation of cerebral blood flow trial-1 is a multi-national open-label study in patients of acute ischaemic stroke in the anterior circulation with National Institutes of Health Stroke Scales 7-20. The treatment initiation will be within 24 h of stroke onset. The ischaemic stroke system is implanted adjacent to the sphenopalatine ganglion via the greater palatine canal using local anaesthesia and a minimally invasive approach. The treatment protocol is constituted as 3-4 h of daily stimulation over 5-7 days. CONCLUSIONS: The implant for augmentation of cerebral blood flow trial-1 will determine the safety and tolerability of the ischaemic stroke system 500 in acute ischaemic stroke as reflected by the incidence of adverse events.

Epilepsy and respiratory chain defects in children with mitochondrial encephalopathies.

OBJECTIVE: The purpose of this study was to determine the relationship between epilepsy and respiratory chain defects in children with mitochondrial encephalopathies (ME). STUDY DESIGN: We conducted a retrospective review of the medical records of children referred for evaluation of an ME. Only patients assigned a definite diagnosis of ME using modified Walker criteria and with a respiratory chain defect were included. Clinical data pertaining to the ME and epilepsy type were collected. Mitochondria were isolated by subcellular fractionation from a vastus lateralis muscle biopsy and studies were performed using polarographic and spectroscopic techniques for the quantitative determination of NADH and cytochrome components of the respiratory chain. RESULTS: A total of 38 children with ME were identified. Seizures were present in 61%. Sixteen of 23 children with epilepsy (70%) had refractory epilepsy associated with a progressive encephalopathy. Children with epilepsy had a significantly higher incidence of complex I defects than children without epilepsy (p<0.01). Complex III and IV defects were significantly higher in patients without epilepsy (p<0.01 and p<0.05, respectively) than in those with epilepsy. CONCLUSIONS: Epilepsy is an important component of ME. The higher incidence of complex I defects in patients with epilepsy suggests a possible relationship between mitochondrial oxidative stress dysfunction and epileptogenic process.

Acute pancreatitis: a lesser-known complication of aluminum phosphide poisoning.

There have been no case reports on aluminum phosphide-induced pancreatitis in the literature available. In this report, we present the case of a young man who developed acute pancreatitis and probably acute myocarditis following ingestion of aluminum phosphide pellets in the absence of the usual risk factors and after exclusion of other possible causes of pancreatitis. In the absence of re-challenge, we put forth the probable causative association of pancreatitis with aluminum phosphide or phosphine gas, its active pesticidal component.

Relapse of herpes encephalitis after acyclovir therapy: report of two new cases and review of the literature.

Relapse of herpes simplex virus (HSV) encephalitis following acyclovir therapy has been reported infrequently in children beyond the neonatal period. The pathogenic mechanism of the recurrence is not fully understood. We report two new cases that support a mechanism of latent HSV infection with reactivation of the disease. Our patients were 2 years (#1) and 8 months (#2) old at initial infection. Both presented with fever, lethargy, focal seizures, and focal motor abnormalities. Serum HSV antibodies (Abs) were negative. The patients were treated with acyclovir for 14 and 21 days, respectively. They were readmitted at 1 month, and 4 days after discharge, respectively, with recurrent lethargy, seizures, and choreo-athetoid movements. Serum and CSF HSV Abs were significantly increased. CSF PCR was positive. In patient # 2 acyclovir-sensitive HSV was isolated from a brain biopsy. Both patients were re-treated with acyclovir, but progressed to a neurovegetative state. In our cases, latent HSV infection and reactivation is the most likely explanation for recurrent encephalitis. The immuno-pathogenic mechanisms of the infection recurrence are discussed. Based on the reported cases in the literature, patients younger than 2 years of age and with lower total dose of acyclovir treatments have a higher risk of recurrence.

Screening interspecific hybrids of Populus (P. ciliata x maximowiczii) using AFLP markers.

Hybrids of Populus ciliata x maximowiczii are very vigorous and outperform both the parents in growth performance and yield. Genetic evaluation of 24 of these interspecific hybrids along with the two mother trees ( Populus ciliata), and five male-parent ( Populus maximowiczii) genotypes was carried out using the AFLP marker assay. Eight AFLP primer combinations detected 428 markers, of which 280 (66%) were polymorphic. Genetic relationships within the samples were evaluated by generating the similarity matrix based on Jaccard's coefficient. The phenetic dendrograms, as well as the PCO plots, separated the hybrids and the two parent species into three distinct clusters. The hybrids grouped closer to the P. ciliata (female parent) cluster as compared to the P. maximowiczii (male parent) cluster. The hybrid cluster contained internal groupings, which correlated to some extent with growth performance. The four best performing hybrids (42m1, 65m1, 23m2, Cm2-5-20/91) formed a distinct sub-cluster. Data from a single primer combination was sufficient for distinguishing the hybrids from the parents and assigning paternity. The hybrids showed 22 markers that were absent in P. ciliata but were monomorphically present in all the hybrids, suggesting outcrossing and common paternity. Further, these 22 markers were found in all the P. maximowiczii genotypes confirming it as the male parent. These male-specific markers can be converted to SCAR markers and used for rapid screening of the P.ciliata x maximowiczii hybrids. The primer combination E-AAC x M-CAA was identified as most suitable for ascertaining true hybridity. AFLP proves to be a useful tool for screening of P. ciliata x maximowiczii hybrids at the early stages of development.

Acute onset paraneoplastic cerebellar degeneration in a patient with small cell lung cancer.

A patient with small cell lung cancer presented with a rare presentation of an acute onset pancerebellar dysfunction. His clinical condition markedly improved following the surgical removal of the tumor and chemo- and radiotherapy.

Novel potential ALL low-risk markers revealed by gene expression profiling with new high-throughput SSH-CCS-PCR.

The current systems of risk grouping in pediatric acute lymphoblastic leukemia (ALL) fail to predict therapeutic success in 10-35% of patients. To identify better predictive markers of clinical behavior in ALL, we have developed an integrated approach for gene expression profiling that couples suppression subtractive hybridization, concatenated cDNA sequencing, and reverse transcriptase real-time quantitative PCR. Using this approach, a total of 600 differentially expressed genes were identified between t(4;11) ALL and pre-B ALL with no determinant chromosomal translocation. The expression of 67 genes was analyzed in different cytogenetic ALL subgroups and B lymphocytes isolated from healthy donors. Three genes, BACH1, TP53BPL, and H2B/S, were consistently expressed as a significant cluster associated with the low-risk ALL subgroups. A total of 42 genes were differentially expressed in ALL vs normal B lymphocytes, with no specific association with any particular ALL subgroups. The remaining 22 genes were part of a specific expression profile associated with the hyperdiploid, t(12;21), or t(4;11) subgroups. Using an unsupervised hierarchical cluster analysis, the discriminating power of these specific expression profiles allowed the clustering of patients according to their subgroups. These genes could help to understand the difference in treatment response and become therapeutical targets to improve ALL clinical outcomes.

A case of emotional facial palsy with ipsilateral anterior inferior cerebellar artery territory infarction.

Emotional facial palsy (EFP) commonly results from anterolateral thalamic or striatocapsular infarcts. Its occurrence in brainstem lesions is uncommon, with previously reported cases being restricted to superior cerebellar artery infarction (3 cases). We report an unusual case of EFP ipsilateral to an anterior inferior cerebellar artery infarction, which opens new insights into the facial corticobulbar tract pathway.

Characterization of a spontaneously arising murine squamous cell carcinoma (SCC VII) as a prerequisite for head and neck cancer immunotherapy.

BACKGROUND: To develop novel therapeutic approaches for patients with head and neck malignancies, poorly immunogenic murine models of squamous cell carcinoma (SCC) need to be defined. METHODS: The phenotype, growth characteristics, and responsiveness to tumor-specific T-cell transfer of a spontaneously arising murine SCC (SCC VII) were characterized. RESULTS: SCC VII expresses major histocompatibility complex (MHC) class I molecules yet is resistant to tumor-specific T-cell killing and relatively insensitive to killing mediated by lymphokine-activated killer (LAK) cells. Intradermal tumors are reproducibly established after vaccination of 5 x 10(4) cells, and systemic micrometastases are apparent after intravenous administration of 2.5 x 10(4) cells. Immunotherapy of 3-day lung metastases using tumor-specific T cells and systemic interleukin-2 (IL-2) was ineffective in reducing the number of metastases in vivo. CONCLUSIONS: SCC VII is a poorly immunogenic murine squamous cell cancer, which represents an ideal model for preclinical testing of immunotherapeutic approaches for patients with SCC of the upper aerodigestive tract.

Treatment of status epilepticus.

Status epilepticus (SE) is a common pediatric emergency, which warrants prompt and aggressive treatment. This report presents a brief description and classification of SE. Therapy should be directed towards rapid termination of the SE, prevention of seizure recurrence and treatment of any underlying cause. A review of drugs commonly used in the treatment of SE is presented. The morbidity and mortality of SE is significant and directly dependant upon prompt and appropriate medical therapy. The treatment of refractory SE requires labour intensive hemodynamic support and suppression of seizures using either barbiturates or anesthetic agent. Formulation and adherence to standard treatment protocols provides the best results.

Neurologic complications of dropsy: from possibility to reality.

Epidemic dropsy, which results from the accidental ingestion of mustard oil adulterated with argemone oil, has been associated with certain neurologic symptoms. The occurrence of objective neurologic involvement has, however, precluded this illness. We report two cases, who were victims of epidemic dropsy in the recent outbreak in India and showed objective neurologic deficit in the form of brachial neuritis.

Wilson's disease--early onset and lessons from a pediatric cohort in India.

OBJECTIVE: To study the clinical profile at presentation and on follow up in cases of Wilson's disease presenting at this hospital. METHODS: Case records of children diagnosed as Wilson's disease (WD) admitted in the hospital or attending the Pediatric outpatient department were retrospectively studied with regard to clinical features, investigations, and family screening at the time of presentation. Note was made of the treatment received by the patients. Clinical profile on follow up was recorded with respect to side effects of treatment, and whether patient improved, deteriorated or remained the same, either from the records or by calling the patient for a follow up, if possible. RESULTS: Analysis of 25 children with Wilson's disease comprising 19 index cases and 6 siblings detected on family screening, revealed mean age of onset for the hepatic presentation was 6.8 years versus 8 years for the neurologic patient. A quarter of index cases has a family history strongly suspicious for Wilson disease which has been earlier overlooked. Clinical presentation was hepatic in 5 patients, purely neurologic in 5, mixed hepatic and neurologic in 9, hemolytic anemia in 1 and polyarthritis in 1. Patients received treatment with D penicillamine, zinc, pyridoxine and low copper diet. Follow upon 18 patients revealed improvement in majority, residual dysarthria in seven,prolonged persistence of KF rings in 15 and complications like renal tubular acidosis with osteopenia in one. CONCLUSION: The early age of onset of symptoms, prolonged KF rings persistence and progression of symptoms among sibs despite therapy is of interest as it may be related to a high copper intake, which may be due to the practice of using brass or copper utensils for cooking Since a large number of children has either a past history of jaundice or sibling deaths due to jaundice or cirrhosis, a high index of suspicion and screening for KF rings is emphasized as a simple and cost effective way of detecting a curable disease at an early stage and family screening of all index cases is imperative. Progression of symptoms among sibs on oral zinc and low dose pencillamine suggests inadequacy of zinc alone for prophylaxis.