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Ashok Srinivasan

Publications and source records attributed to Ashok Srinivasan.

At least 19 recordsLinked to original sources
PubMed2006

Acute anterior circulation stroke: recanalization using clot angioplasty.

BACKGROUND AND PURPOSE: Different strategies have been employed to recanalize acutely occluded middle cerebral and internal carotid arteries (ICA) in the setting of acute stroke including intravenous and intra-arterial tPA. However, pharmaceutical thrombolysis alone, may not be effective in patients with a large amount of clot volume (complete M1, terminal internal carotid artery). We report our initial experience with endovascular clot disruption using a soft silicone balloon in addition to intravenous or intra-arterial thrombolysis with tPA. METHODS: This is a retrospective review of nine patients with symptoms of acute stroke from clot in the middle cerebral or internal carotid territories who were treated with intracranial balloon angioplasty. All patients presented with symptoms of acute anterior circulation stroke less than six hours from onset. Patients in whom computed tomography (CT) angiography confirmed the presence of large vessel clot (terminal ICA, M1 or proximal M2) were included in the study. A CT perfusion was performed providing maps of cerebral blood volume, flow and mean transit time. If the patient presented less than three hours from onset then intravenous tissue plasminogen activator (tPA) was also administered. Intra-arterial tPA was delivered into the clot. If the volume of clot was judged to be significant by the treating neurointerventionist, then a limited trial of tPA was administered intra-arterially followed by balloon angioplasty of persistant clot. The time from imaging to vessel recanalization was recorded. Clinical outcomes were assessed using the modified Rankin scale and Barthel Index. RESULTS: Diagnostic CT perfusion studies were performed in 7 (78%), all of which showed a significant amount of salvageable tissue as judged by the treating neurointerventionist and neurologist. Recanalization (TIMI 2 or 3) was possible in 8 (89%). There were no cases of symptomatic intracranial hemorrhage and 2 (22%) asymptomatic hemorrhages. The average time from performance of the initial emergency CT to vessel recanalization was 2.1 hours with mean time from symptom onset to vessel recanalization of 4.1 hours. Five (56%) patients had good outcomes, 1 (11%) had mild and 3 (33%) had moderate to severe disability. CONCLUSION: Clot angioplasty can potentially shorten recanalization times in well-selected patients and can be an effective complimentary procedure in patients with tPA resistant clot. Angioplasty can be performed with a very low complication rate using the technique described and may be associated with good outcomes.

Aged↗
PubMed2006

State-of-the-art imaging of acute stroke.

Stroke is a leading cause of mortality and morbidity in the developed world. The goals of an imaging evaluation for acute stroke are to establish a diagnosis as early as possible and to obtain accurate information about the intracranial vasculature and brain perfusion for guidance in selecting the appropriate therapy. A comprehensive evaluation may be performed with a combination of computed tomography (CT) or magnetic resonance (MR) imaging techniques. Unenhanced CT can be performed quickly, can help identify early signs of stroke, and can help rule out hemorrhage. CT angiography and CT perfusion imaging, respectively, can depict intravascular thrombi and salvageable tissue indicated by a penumbra. These examinations are easy to perform on most helical CT scanners and are increasingly used in stroke imaging protocols to decide whether intervention is necessary. While acute infarcts may be seen early on conventional MR images, diffusion-weighted MR imaging is more sensitive for detection of hyperacute ischemia. Gradient-echo MR sequences can be helpful for detecting a hemorrhage. The status of neck and intracranial vessels can be evaluated with MR angiography, and a mismatch between findings on diffusion and perfusion MR images may be used to predict the presence of a penumbra. The information obtained by combining various imaging techniques may help differentiate patients who do not need intravenous or intraarterial therapy from those who do, and may alter clinical outcomes.

Angiography↗
PubMed2005

Left ventricular functional recovery with percutaneous, transvascular direct myocardial delivery of bone marrow-derived cells.

BACKGROUND: The potential for cellular cardiomyoplasty to provide functional left ventricular recovery in the chronically injured heart remains unclear. METHODS: Yorkshire swine (n = 10; 35-50 kg) had anterolateral myocardial infarction (MI) induced by coil embolization of the left anterior descending artery. Approximately 5 weeks post-MI, a composite, intravascular ultrasound-guided catheter system (TransAccess) was used to deliver an autologous, labeled, bone marrow-derived cell sub-population (approximately 3 x 10(8) cells) or saline control (approximately 50 injections/arm) through coronary veins directly into infarct and peri-infarct myocardium. Two months post-transplant, the animals had blinded endocardial and epicardial left ventricular electrical scar mapping and biventricular electrical stimulation. Coronary angiography and quantitative biplane ventriculography were performed at baseline, transplant, and sacrifice time-points. RESULTS: Robust, viable, predominantly desmin-negative cell grafts were demonstrated post-mortem in all treatment animals. Baseline and pre-transplant global and regional wall motion was similar between groups. The cell treatment group demonstrated functional recovery with a left ventricular ejection fraction of 38.1% at the time of transplant increasing to 48.5% (p = 0.005) at sacrifice, whereas the control arm was unchanged (38.0% vs 34.3%, respectively; p = NS). The regional improvement corresponded with a reduction in percentage of hypokinetic (52.1%-42.9%, p = 0.002) and percentage of akinetic (24.8%-17.7%, p = 0.04) segments in the cell-treated animals. Epicardial scar area was not different (37 cm2 vs 23 cm2, p = 0.37) between groups. CONCLUSIONS: Percutaneous, transvascular, direct intramyocardial bone marrow cell transplantation is safe and feasible in chronically infarcted tissue. In this pilot study, cell therapy improved overall left ventricular systolic function by recruiting previously hypokinetic or akinetic myocardial tissue.

Animals↗
PubMed2005

Processing and interpretation times of CT angiogram and CT perfusion in stroke.

OBJECTIVE: To determine the mean time for acquiring computed tomogram perfusion (CTP) and CT angiogram (CTA) images in acute stroke. To determine and compare processing and interpretation times amongst three groups of radiologists with varying degree of expertise: two radiology residents (Group I), two neuroradiology fellows (Group II) and four consultant neuroradiologists (Group III). METHODS: The mean time of acquisition of CTA and CTP studies was calculated among ten patients presenting with acute stroke. All readers had to process the CTA and CTP images, interpret them (for presence or absence of thrombus and penumbra) and save them on the GE Advantage Windows workstation. The mean time for processing and interpreting these studies was calculated. RESULTS: The mean time for acquisition of CTA and CTP studies in the ten patients was 14.6 +/- 5.9 minutes. The time taken for CTA processing and interpretation in Groups I, II and III was 2.3 +/- 1.3 min, 1.6 +/- 0.4 min and 1.5 +/- 0.7 min respectively. The time required for CTP processing and interpretation by the same groups was 5.2 +/- 1.7 min, 4.5 +/- 1.5 min and 4.1 +/- 1.1 min respectively. There was a statistically significant difference of means between Groups I and III in the CTA and CTP processing and interpretation times (p=0.02, p=0.01 respectively) but no statistical difference between Groups I and II (p=0.15, p=0.22 respectively) or Groups II and III (p=0.31, p=0.30 respectively). CONCLUSION: The CTA and CTP studies can be performed, processed and interpreted quickly in acute stroke.

Adult↗
PubMed2004

DRAGON: a member of the repulsive guidance molecule-related family of neuronal- and muscle-expressed membrane proteins is regulated by DRG11 and has neuronal adhesive properties.

DRG11, a transcription factor expressed in embryonic dorsal root ganglion (DRG) and dorsal horn neurons, has a role in the development of sensory circuits. We have used a genomic binding strategy to screen for the promoter region of genes regulated by DRG11. One gene with a promoter region binding to the DNA binding domain of DRG11 encodes a novel membrane-associated [glycosyl-phosphatidylinositol (GPI)-anchored] protein that we call DRAGON. DRAGON expression is transcriptionally regulated by DRG11, and it is coexpressed with DRG11 in embryonic DRG and spinal cord. DRAGON expression in these areas is reduced in DRG11 null mutants. DRAGON is expressed, however, in the neural tube before DRG11, and unlike DRG11 it is expressed in the brain and therefore must be regulated by other transcriptional regulatory elements. DRAGON shares high sequence homology with two other GPI-anchored membrane proteins: the mouse ortholog of chick repulsive guidance molecule (mRGM), which is expressed in the mouse nervous system in areas complementary to DRAGON, and DRAGON-like muscle (DL-M), the expression of which is restricted to skeletal and cardiac muscle. A comparative genomic analysis indicates that the family of RGM-related genes--mRGM, DRAGON, and DL-M--are highly conserved among mammals, zebrafish, chick, and Caenorhabditis elegans but not Drosophila. DRAGON, RGM, and DL-M mRNA expression in the zebrafish embryo is similar to that in the mouse. Neuronal cell adhesion assays indicate that DRAGON promotes and mRGM reduces adhesion of mouse DRG neurons. We show that DRAGON interacts with itself homophilically. The dynamic expression, ordered spatial localization, and adhesive properties of the RGM-related family of membrane-associated proteins are compatible with specific roles in development.

Amino Acid Sequence↗
PubMed2004

Tissue-engineered small intestine improves recovery after massive small bowel resection.

OBJECTIVE: Rescue with tissue-engineered small intestine (TESI) after massive small bowel resection (MSBR). SUMMARY BACKGROUND DATA: Short bowel syndrome is a morbid product of massive small bowel resection. We report the first replacement of a vital organ by tissue engineering with TESI after MSBR. METHODS: Ten male Lewis rats underwent TESI implantation with green fluorescent protein (GFP)-marked cells (TESI+, n = 5) or sham laparotomy (TESI-, n = 5) followed by MSBR. Side-to-side anastomosis of TESI to proximal small intestine was performed or omitted. TESIO animals underwent implantation of engineered intestine with no further surgery. Weights were measured QOD until day 40. Transit times were measured. DNA assay was performed with computer morphometry. Northern blots of RNA were probed for intestinal alkaline phosphatase (IAP) and villin. Hematoxylin and eosin, S100, and smooth muscle actin immunohistochemistry were performed. Blood was collected at sacrifice. RESULTS: All 10 rats initially lost then regained weight. The initial rate of weight loss was higher in TESI+ versus TESI-, but the nadir was reached a week earlier with more rapid weight gain subsequently to 98% preoperative weight on day 40 in animals with engineered intestine versus 76% (P < 0.03). Serum B12 was higher at 439 pg/mL versus 195.4 pg/mL. IAP mRNA appeared greater in TESI+ than TESIO, with constant villin levels. Histology revealed appropriate architecture including nerve. GFP labeling persisted. CONCLUSIONS: Anastomosis of TESI significantly improved postoperative weight and B12 absorption after MSBR. IAP, a marker of differentiation in intestinal epithelium, is present in TESI, and GFP labeling was accomplished.

Actins↗
PubMed2003

Spondylo-megaepiphyseal-metaphyseal dysplasia: an unusual bone dysplasia.

A rare case of spondylo-megaepiphyseal-metaphyseal dysplasia is reported in a 10-year-old boy. The features were metaphyseal dysplasia, markedly defective ossification of vertebral body centres and enlarged epiphyses. Although it shares some features with spondylo-metaphyseal dysplasia, oto-spondylo-megaepiphyseal dysplasia and cleidocranial dysplasia, the presence of several unusual radiological findings sets it apart.

Child↗
PubMed2003

Tissue-engineered stomach: a preliminary report of a versatile in vivo model with therapeutic potential.

BACKGROUND/PURPOSE: Microgastria and postgastrectomy morbidities are substantial. The authors hypothesized a functional living tissue-engineered stomach could function as a replacement alternative. METHODS: Stomach organoid units, mesenchymal cores surrounded by epithelia, were isolated from neonatal and adult rats and transplanted paratopically on biodegradable polymer tubes, which were implanted in syngeneic hosts, varying the inclusion of stomach regions. Four weeks later, tissue-engineered stomach (TES) was either harvested or anastomosed. GFP labeling was performed before implantation. Histology and immunohistochemical detection of the antigensgastrin and actin smooth muscle were performed. RESULTS: Ninety-eight percent of all animals generated TES, including TES formation from adult tissue. Immunohistochemistry for alpha-actin smooth muscle and gastrin confirms the presence of a smooth muscle layer and a well-developed gastric epithelium containing all the elements of the native rat stomach including gastric pits and squamous layers, varying by included regions at harvest. TES architecture was maintained in anastomosis: GFP-labeled TES maintained signal in anastomosis, proving the donor origin of the TES. CONCLUSIONS: TES resembles native stomach and maintains robust histology in anastomosis, a new versatile model for the study of gastric physiology and possible therapy.

Actins↗
PubMed2003

Tissue-engineered esophagus: experimental substitution by onlay patch or interposition.

OBJECTIVES: We proposed to fabricate a tissue-engineered esophagus and to use it for replacement of the abdominal esophagus. METHODS: Esophagus organoid units, mesenchymal cores surrounded by epithelial cells, were isolated from neonatal or adult rats and paratopically transplanted on biodegradable polymer tubes, which were implanted in syngeneic hosts. Four weeks later, the tissue-engineered esophagus was either harvested or anastomosed as an onlay patch or total interposition graft. Green Fluorescent Protein labeling by means of viral infection of the organoid units was performed before implantation. Histology and immunohistochemical detection of the antigen alpha-actin smooth muscle were performed. RESULTS: Tissue-engineered esophagus grows in sufficient quantity for interposition grafting. Histology reveals a complete esophageal wall, including mucosa, submucosa, and muscularis propria, which was confirmed by means of immunohistochemical staining for alpha-actin smooth muscle. Tissue-engineered esophagus architecture was maintained after interposition or use as a patch, and animals gained weight on a normal diet. Green Fluorescent Protein-labeled tissue-engineered esophagus preserved its fluorescent label, proving the donor origin of the tissue-engineered esophagus. CONCLUSIONS: Tissue-engineered esophagus resembles the native esophagus and maintains normal histology in anastomosis, with implications for therapy of long-segment esophageal tissue loss caused by congenital absence, surgical excision, or trauma.

Actins↗
PubMed2003

Acute lymphoblastic leukemia presenting with lactic acidosis and renal tubular dysfunction.

Acute lymphoblastic leukemia (ALL) in children can rarely present with severe lactic acidosis in the absence of a high white blood cell count or other complications. Renal tubular dysfunction with hypercalciuria and hypocalcemia in the absence of pre-existing renal disease or concurrent medications has not been described at presentation in childhood ALL. The authors describe a 7-year-old boy with ALL presenting with severe lactic acidosis and renal tubular dysfunction, both of which were refractory to conventional management and resolved rapidly with appropriate chemotherapy.

Acidosis, Lactic↗