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.

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.

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.

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.

Organophosphorus intoxication.

In every period of history, military leaders have wrestled between a desire to gain victory by using every possible means and a revulsion from resorting to poison. During the First World War, a European country cast aside the humanitarian tradition of its poets and philosophers and attacked its enemies with a wave of chlorine gas; the same nation, 30 years later, put to death 6 million human beings in gas chambers. But out of the industry of war gases, a few organophosphorus compounds, notably tabun and sarin, later underwent large-scale development. These compounds are nowadays used primarily as insecticides. Several early citations on organophosphate compounds place this chemical class in neurological context. However, as evidenced by events during the Gulf War of 1991 and the United Nations' arsenal inspections during that war, military interests in organophosphates are medically very pertinent today, beyond just historical allusions.

Vertebral artery dissection: issues in diagnosis and management.

Vertebral artery dissection is an uncommon cause of stroke in children. Accuracy of diagnosis by magnetic resonance angiography (MRA) instead of invasive transfemoral angiography (TFA) has been controversial. The need for anticoagulation and duration of such therapy is also arguable. We report 2 boys with vertebral artery dissection: one, aged 7 years, presented with hemiparesis and seizures and the other, aged 4 years, presented with ataxia. Each boy's initial MRA was not interpreted as delineating occlusive lesions to explain the posterior circulation infarcts visualized on computed tomography and magnetic resonance imaging scans. However, subsequent MRAs were suspicious for vertebral artery dissection, which was confirmed by TFA. Both children were treated with anticoagulation therapy. The first patient continued to manifest evidence of new infarcts despite treatment (initially with aspirin alone, followed by anticoagulation with heparin and warfarin), and is now maintained on a combination of high dose warfarin and aspirin. The second patient is now maintained on aspirin alone after initial anticoagulation for 6 months with heparin followed by warfarin. A high index of suspicion for vertebral artery dissection may allow diagnosis on the basis of MRA alone. Previous reports have indicated good outcomes of vertebral artery dissection in children and adults irrespective of anticoagulation treatment. Our experience suggests that anticoagulation may be beneficial in preventing further strokes caused by the dissection.

MRI signal changes in the white matter after corpus callosotomy.

Magnetic resonance imaging (MRI) changes reported after corpus callosotomy include hyperintensity in the corpus callosum, perifalcine hyperintensity caused by surgical retraction, and acute changes associated with surgical complications. The authors have observed MRI signal changes in the cerebral white matter of corpus callosotomy patients that are separate from the sectioned callosum and not clearly related to surgical manipulation or injury. Brain MRI scans were retrospectively reviewed in 25 of 38 patients who underwent anterior, posterior, or total callosotomy for refractory seizures between 1988 and 1995. Nine patients had signal changes in the cerebral white matter on postoperative MRI. Six of these patients had preoperative MRI studies available for comparison, and none of the white matter signal abnormalities were evident preoperatively. T2 prolongation or hyperintensity on proton-density images was observed in areas including the centrum semiovale, forceps major, and forceps minor. Three patients had signal changes that had distinct borders extending only to the posterior limit of the callosotomy. MRI signal changes in the cerebral white matter after corpus callosotomy have not been previously reported and may represent distant effects of callosal section. Wallerian degeneration occurring in the neuronal processes cut during surgery could account for the signal changes.

Open reduction and fixation of proximal humeral fractures and fracture-dislocations.

Open reduction and internal fixation was employed in the treatment of 25 severely displaced fractures and fracture-dislocations of the proximal humerus. Our aims were accurate reduction and stable fixation to allow early mobilisation and to achieve full functional recovery. In 15 fractures an AO T-plate was used and in 10 a bent semitubular plate was employed as a blade plate. Excellent or satisfactory results were obtained in all six patients with two-part fractures involving the surgical neck; in four of the five patients with three-part fractures involving the surgical neck and tuberosities; in nine of the 11 patients with fracture-dislocation; and in two of the three patients with split fractures of the humeral head. Overall results were good or satisfactory in 21 of the 25 cases. Unsatisfactory results were associated with rotator cuff damage.

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.

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.

Reappearing CT lesions: 4 cases.

An overwhelming majority of disappearing CT lesions in India have been aetiologically linked to cysticercosis. We report 4 patients with disappearing CT lesions in whom the lesion later reappeared at the same (3 patients) or different site (1 patient). One patient was a Taenia carrier. Serial MRI evaluation in one patient revealed a persisting lesion in the interval period. The contribution of these observations towards the understanding of the aetiology of disappearing CT lesions is discussed.

The Spectrum and clinical correlates of electrodiagnostic abnormalities in acute organophosphorus poisoning : a study of 55 patients.

Electrodiagnostic findings in 55 patients with acute organophosphorus intoxication have been correlated with clinical severity. Patients were assigned 3 grades of intoxication, depending upon the clinical severity of poisoning, muscarinic and nicotinic manifestations, ventilatory failure and altered sensorium. Repetitive responses upon single supramaximal stimulation of the median motor nerve were noted in all three grades of intoxication. In mild intoxication (grade I), low frequency repetitive nerve stimulation (< 3 Hz) produced no change in the amplitudes of the successive compound muscle action potentials. High frequency repetitive nerve stimulation (30 Hz and 50 Hz) resulted in either incremental responses (18 out of 29 cases), decremental responses (5 out of 29 cases) or decremental - incremental responses (6 out of 29 cases). Thirty five electrodiagnostic evaluations were performed in patients with overt neuromuscular weakness but not requiring mechanical ventilation (grade 2). Decremental responses were noted in only 3 instances at low frequency (< 3 Hz) repetitive nerve stimulation and in 34 out of 35 cases with high rates of stimulation. Patients who required mechanical ventilation had decremental responses at high (30 and 50 Hz) (12 out of 12 cases) as well as low rates (3 and 5 Hz) (7 out of 12 cases) of repetitive nerve stimulation. Serial electrodiagnostic evaluations, which were done in 12 patients, revealed that neuromuscular transmission abnormalities were either mild or absent within 24 hours in 9 patients. A deterioration in the neuromuscular transmission studies was noted during subsequent examinations performed, 1- 4 days later in these 9 patients. Electrodiagnostic testing is highly sensitive for establishing a diagnosisof organophosphorus poisoning and correlates well with clinical findings and the severity of poisoning. It may, however be normal in the early stages of intoxication.

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.

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.

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.

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.