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Biomedical subjects

V Ganesan

Publications and source records attributed to V Ganesan.

At least 19 recordsLinked to original sources

A proposed classification for subtypes of arterial ischaemic stroke in children.

The aim of this study was to propose a classification system for childhood arterial ischaemic stroke (AIS). Subtypes from the Trial of Org 10172 in Acute Stroke Therapy (TOAST) classification, previously shown to be applicable to children, were retained in the proposed Paediatric Stroke Classification (PSC). Additional important paediatric AIS aetiologies were identified from a literature review. Preliminary validation was performed by three raters who categorized clinical vignettes from 135 patients (66 male; median age 6.3 y, range 0.1 to 16 y). Eight aetiological subtypes were identified and defined, as follows: (1) sickle cell disease; (2) cardioembolic; (3) moyamoya syndrome; (4) cervical arterial dissection; (5) steno-occlusive cerebral arteriopathy; (6) other determined aetiology; (7) multiple probable/possible aetiologies; and (8) undetermined aetiology. There was very good agreement between the raters about categorization of the vignettes. Causes of disagreement were identified and final categories and definitions were modified accordingly. We conclude that the PSC enables the categorization of children with AIS into aetiological subtypes relevant to this age group. This will be useful in multicentre studies of natural history and treatment but will require further independent validation.

Adolescent↗

Thrombophilia and first arterial ischaemic stroke: a systematic review.

AIMS: To undertake a systematic review of the literature reporting the prevalence of thrombophilia in children with a first arterial ischaemic stroke (AIS). METHODS: Systematic review of case-control studies reporting data for prevalence of protein C, S, and antithrombin (AT) deficiencies, activated protein C resistance (APCr), total plasma homocysteine >95th centile, the thrombophilic mutations factor V1691 GA, prothrombin 20210GA, and MTHFR C677T in children with first, radiologically confirmed, AIS. RESULTS: Of 1437 potentially relevant citations, 18 met inclusion criteria. A total of 3235 patients and 9019 controls had been studied. Results of meta-analyses were expressed as pooled odds ratios (OR) relating the prevalence of the thrombophilic condition in children with AIS to that in controls. The pooled OR (and 95% CI) were: protein C deficiency, 6.49 (2.96 to 14.27); protein S deficiency, 1.14 (0.34 to 3.80); AT deficiency, 1.02 (0.28 to 3.67); APCr, 1.34 (0.16 to 11.52); FV1691 GA, 1.22 (0.80 to 1.87); PT20210GA, 1.10 (0.51 to 2.34); MTHFR C677T, 1.70 (1.23 to 2.34); and total plasma homocysteine >95th centile, 1.36 (0.53 to 3.51). There was no statistical heterogeneity within these data. CONCLUSIONS: All factors examined were more common in children with first AIS than in controls, and significantly so for protein C deficiency and the MTHFR C677T mutation. The implications of thrombophilia for prognosis and recurrence need to be established before clinical recommendations can be made regarding investigation and treatment of children with AIS.

Brain Ischemia↗

Radiosurgery planning supported by the GEMSS grid.

GEMSS (Grid Enabled Medical Simulation Services IST-2001-37153) is an EU project funded to provide a test bed for Grid-enabled health applications. Its purpose is evaluation of Grid computing in the health sector. The health context imposes particular constraints on Grid infrastructure design, and it is this that has driven the feature set of the middleware. In addition to security, the time critical nature of health applications is accommodated by a Quality of Service component, and support for a well defined business model is also included. This paper documents experience of a GEMSS compliant radiosurgery application running within the Medical Physics department at the Royal Hallamshire Hospital in the UK. An outline of the Grid-enabled RAPT radiosurgery application is presented and preliminary experience of its use in the hospital environment is reported. The performance of the software is compared against GammaPlan (an industry standard) and advantages/disadvantages are highlighted. The RAPT software relies on features of the GEMSS middleware that are integral to the success of this application, and together they provide a glimpse of an enabling technology that can impact upon patient management in the 21st century.

Decision Support Systems, Clinical↗

Dewetting of polymeric films: unresolved issues.

Since the early seminal theoretical work by Brochard and coworkers, and experiments by Reiter over a decade ago, considerable progress has been made toward the development of a comprehensive picture of the "equilibrium" and dynamic behavior of unstable thin polymeric films. Generally, theoretical work has carefully guided the design of many experiments conducted in this field. Recent experimental findings, however, raise new questions that could probably not have been foreseen by theory and now need to be revisited. In this paper we highlight three problems in two general areas, (1) the use of the effective interfacial potential describing film substrate interactions and (2) the dynamics of dewetting and the associated connection to "slip" phenomena and fingering instabilities. We suggest that in addition to experiments, analytical theory and simulations will play a critical role toward elucidating the ultimate goal of a universal picture of "equilibrium" and dynamic behavior of instabilities in thin films.

Journal Article↗

Atomic force microscopic studies on erythrocytes from an evolutionary perspective.

We examined atomic force microscopy (AFM) and lateral force microscopy (LFM) images of human, avian, reptilian, amphibian, and piscine erythrocytes to determine whether the general pattern of erythrocyte membrane architecture has been largely conserved in the course of phylogenetic evolution or relatively minor modifications have taken place. The general pattern of the cell surface structure is indeed very similar among the phyla examined. The surface features include a number of blebs or globular structures and hole-like depressions. Such features are particularly clear in fish (Heteropneustes sp.), in which globular blebs are arranged in tiers around the depressions. The same pattern is found in the other phyla, although the sizes of the blebs and depressions vary. The depressions are approximately 340 and approximately 100 nm in diameter in chickens and fish, respectively, and are smaller in other phyla. The images of human erythrocytes presented here show holes more clearly than the images obtained by Zhang et al. (Scanning Electron Microsc., 1995; 9:981-989), who showed for the first time the highly uneven surface of these cells. The globules range in size from approximately 50-150 nm in diameter. These nanostructures have a width of approximately 333-1,000 atoms, assuming that the average dimension of an atom is 1.5 A. The size range of the holes is approximately 40-432 nm (equivalent to a width of approximately 266-2880 atoms). LFM images, which take into account the lateral component of the force, represent the variation of surface friction (roughness) on the erythrocyte surface. This is very clear in the toad images, which show well-ordered strata that have not been revealed in ordinary AFM images.

Animals↗

Ischaemic stroke subtypes in children and adults.

Ischaemic stroke subtypes in children and adults were compared to determine the similarity in aetiologies. Thirty-six children (22 females, 14 males; median age 5 years 7 months, range 6 weeks to 15 years 10 months) and 50 adults (35 males, 15 females; median age 44 years, range 17 years 2 months to 49 years 11 months) who had presented with ischaemic stroke between 1995 and 2000, were categorized using a modified version of the Trial of Org 10172 in Acute Stroke Therapy (TOAST) classification. Proportions of patients in the subtypes of the TOAST classification system were significantly different in the two groups (chi2 test, p<0.01). The first three subtypes (large artery atherosclerosis, cardioembolic, and small vessel disease) accounted for the majority of adult strokes (27 of 50). In contrast, only three of 36 children were accounted for within these three subtypes. The majority of children (29 of 36) were classified within the 'other determined aetiology' subtype. Aetiology was undetermined in 12 of 50 adults compared with three of 36 children. Causes of ischaemic stroke in children and adults are distinct. A classification system for ischaemic stroke in children would be useful for collaborative studies.

Adolescent↗

Arterial dissection complicating tonsillectomy.

Tonsillectomy is a frequently performed surgical procedure. Surgical complications can be serious. We report the case of a 7-year-old female who experienced an arterial ischaemic cerebral infarction following elective adenotonsillectomy.

Aortic Dissection↗

Can mild head injury cause ischaemic stroke?

Five cases of ischaemic stroke preceded by minor head trauma in children are described. All patients had striatocapsular infarction. Three had no cerebrovascular abnormality; two had turbulent flow in the proximal middle cerebral artery. None of the patients had evidence of arterial dissection or any other risk factors for stroke. All made an excellent neurological recovery. Possible mechanisms include mechanical disruption to the flow in the perforating branches of the middle cerebral artery, intimal trauma and subsequent thrombosis, or arterial spasm induced by trauma. The specific susceptibility in affected children remains unexplained; both genetic and environmental factors (for example, previous chickenpox) may be implicated.

Child↗

Posterior circulation stroke in childhood: risk factors and recurrence.

OBJECTIVE: To ascertain whether posterior circulation stroke in children has distinctive clinical or radiologic features. METHODS: Patients were identified retrospectively from two pediatric neurology centers. Clinical details were ascertained by chart review, and radiologic data were reviewed by three neuroradiologists. RESULTS: Twenty-two cases were identified (17 boys). Twenty children had evidence of vertebrobasilar arterial abnormalities, which were multifocal in 12. The etiology of these was vertebral artery dissection in 10 cases and unclear in the remaining 10. Cardiac abnormalities were rare (n = 4). Other risk factors for stroke in childhood were hypertension (n = 9), the thermolabile methylene tetrahydrofolate reductase gene mutation (n = 4), and the factor V Leiden mutation (n = 2). Two children had subluxation of the upper cervical spine at the extreme of normal limits. In follow-up for 6 months to 11 years (median 4 years), five patients had further strokes and seven had TIA. Overall, 12 patients had no residual neurologic deficits. CONCLUSIONS: The male preponderance, frequency of arterial dissection, rarity of cardiac embolism, and >20% recurrence were notable. Cerebral angiography is usually indicated if a definitive diagnosis is not made on MRI. Additional investigations should include echocardiography and cervical spine radiography in flexion and extension.

Adolescent↗

MR perfusion imaging in Moyamoya Syndrome: potential implications for clinical evaluation of occlusive cerebrovascular disease.

BACKGROUND AND PURPOSE: Ischemic symptoms in patients with moyamoya syndrome (MMS) are usually due to hemodynamically mediated perfusion failure, and identification of abnormal tissue perfusion in these patients is therefore clinically important. Although dynamic susceptibility contrast (DSC) MRI can be used to study tissue perfusion, there are potential technical problems in MMS. This study investigates the scope and limitations of perfusion MRI in the clinical evaluation of such patients. METHODS: Thirteen patients with bilateral MMS were studied with the use of structural, diffusion, and perfusion MRI. The DSC MRI data were analyzed both visually and by a quantitative regional analysis, and the relationship between perfusion status and clinical symptoms was investigated. RESULTS: Extensive bilateral DSC MRI abnormalities were observed in all the patients. There was a very heterogeneous distribution of bolus arrival time. The areas of abnormality included the major arterial border zones in all cases, although these usually appeared normal on structural and diffusion MRI. Only the most clinically unstable patients had peak width (defined as time to peak minus bolus arrival time) >5 seconds on the quantitative regional analysis. Several technical limitations of perfusion quantification in MMS are described, as well as the implications of these limitations in patients with other forms of occlusive large-vessel disease. CONCLUSIONS: The technical limitations of DSC MRI described in this study are important for the accurate interpretation of perfusion MRI in MMS. Despite these limitations, these preliminary findings suggest that the use of quantitative regional analysis of summary parameters may provide clinically useful information in patients with MMS.

Adolescent↗

Salicylic acid response in rice: influence of salicylic acid on H(2)O(2) accumulation and oxidative stress.

We have studied the accumulation of hydrogen peroxide in rice leaves in response to salicylic acid (SA) treatment. H(2)O(2) accumulation was localized in the veins. While the activity of the H(2)O(2) degrading enzyme peroxidase was inhibited in response to SA, superoxide dismutase activity, which generates H(2)O(2), did not show any change. An increase in the activity of glutathione reductase, a peroxide degrading enzyme, was observed upon SA treatment, similar to the response reported by accumulation of active oxygen species. In rice leaves transformed with CaMV-GUS fusions, we found that SA treatment induced transcriptional activation through as-1 element. As-1 has been implicated in protective mechanisms that operate during some types of oxidative stress and the hypersensitive response (HR). Expression of rice pathogenesis-related protein 5 (PR5), one of the PR genes associated with systemic acquired resistance, was induced by SA. This induction seems to be independent of the H(2)O(2) accumulation induced by SA. Inoculation of rice leaves with the rice blast fungus, Magneporthe grisea, also led to the accumulation of H(2)O(2) in the veins, suggesting the presence of common signals between SA and pathogen responses. Thus SA application seems to induce oxidative stress in rice through H(2)O(2); a signal molecule implicated in biotic and abiotic stress responses.

Journal Article↗

Characteristics and course of urinary tract dysfunction after acute transverse myelitis in.

Bladder involvement is common in transverse myelitis but its characteristics and natural history, particularly in relation to neurological outcome, have not been described in a paediatric population previously. Ten children, with ages ranging from 8 months to 16 years, who had a diagnosis of acute transverse myelitis were studied with video urodynamics and followed up in a tertiary paediatric neurourology clinic. Nine of ten children had obstructive urinary tract symptoms at presentation and all went on to develop 'irritative' urinary tract symptoms (frequency and urgency) about 1 month after initial presentation. Video urodynamics showed a combination of irritative (detrusor hyperreflexia) and obstructive (detrusor-sphincter dyssynergia) abnormalities in most patients and enabled management to be specifically directed towards these. The patients progress was followed up for a median duration of 36 months. All had residual bladder dysfunction, only four were asymptomatic on treatment. The degree of recovery of bladder function was not related to the degree of motor recovery.

Adolescent↗

Obsessive--compulsive disorder and psychosis.

OBJECTIVE: To study the phenomenology, treatment, course, and outcome of patients with comorbid obsessive-compulsive disorder (OCD) and psychotic features. METHOD: A retrospective chart analysis was conducted on 15 patients with OCD with psychotic features. Data were collected regarding patient demographics, psychiatric diagnosis, duration of illness, treatment details, and clinically determined outcome over time. RESULTS: Obsessive doubts, washing, and checking compulsions were the most commonly seen obsessive-compulsive (OC) symptoms. Of the patients, 53% had first-rank symptoms, and 77% showed significant improvement on treatment with a combination of antipsychotic and antiobsessional drugs. CONCLUSIONS: The observed improvement on treatment with a combination of antiobsessional and antipsychotic drugs supports the use of combination treatment in patients who have both OC and psychotic symptoms.

Adult↗

Outcome after ischaemic stroke in childhood.

A parental questionnaire was used to investigate the outcome for children who had had ischaemic stroke, who were seen at Great Ormond Street Hospital, London between 1990 and 1996. The results of functional assessments carried out by a physiotherapist and an occupational therapist, and of quantitative evaluations carried out by a neuropsychologist were used for validation where possible. The relationship between clinical and radiological factors and outcome were examined. The children were aged between 3 months and 15 years at the time of stroke (median age 5 years) and the period of follow-up ranged from 3 months to 13 years (median duration 3 years). Of the 90 children for whom data were obtained, 13 (14%) had no residual impairments. Outcome was good in 37 children (40%) and poor in 53 (60%) (defined according to whether impairments interfered with daily life). Agreement, as measured by Cohen's kappa, was good or very good between the parents' responses and the qualitative measures provided by the medical professionals and the therapists, but only fair to moderate for the quantitative measures provided by the neuropsychologists. This may reflect different parental perceptions of the physical and cognitive aspects of outcome. Younger age at time of the stroke was the only significant predictor of adverse outcome.

Adolescent↗

Molecular wall effects: are conditions at a boundary "boundary conditions"?

This paper addresses and answers "no" to the question of whether the literal molecular-dynamically-derived species velocities prevailing at a solid surface bounding a two-component fluid continuum undergoing molecular diffusion constitute the appropriate species-velocity boundary conditions to be imposed upon the fluid continuum. In a broader context, generic boundary condition issues arising from the presence of different length scales in continuum-mechanical descriptions of physical phenomena are clarified. This is achieved by analyzing a model problem involving the steady-state diffusion of a dilute system of Brownian spheres (the latter envisioned as tractable models of solute "molecules") through a quiescent viscous solvent continuum bounded laterally by solid plane walls. Both physicochemical (potential energy) and hydrodynamic (steric) wall interaction effects experienced by the Brownian spheres are explicitly accounted for in our refined, microscale continuum model of the diffusion process. Inclusion of these "solid-wall-fluid" (s-f ) boundary-generated forces [above and beyond the usual "fluid-fluid" (f-f ) intermolecular forces implicit in the conventional Fick's law macroscale continuum description] serves to simulate the comparable s-f molecular boundary forces modeled in molecular dynamics simulations of the diffusional process. A singular perturbation framework is used to clarify the physical interpretation to be ascribed to "continuum-mechanical boundary conditions." In this same spirit we also clearly identify the origin of the physical concept of a "surface field" as well as of the concomitant surface transport conservation equation for strongly adsorbed species at solid walls. Our analysis of such surface phenomena serves to emphasize the fact that these are asymptotic, surface-excess, macroscale concepts assigned to a surface, rather than representing literal molecular material entities physically confined to the surface. Overall, this paper serves to illustrate the manner in which molecular simulations need to account for these different length scales and corresponding scale-dependent concepts if such analyses are to avoid drawing incorrect inferences regarding the molecular origins of continuum-mechanical boundary conditions.

Journal Article↗

Risk factors for arterial ischemic stroke in children.

Since early recurrence occurs in at least 10% of patients presenting with their first stroke in childhood in the reported series, the search for modifiable risk factors should be a priority. Risk factors for stroke in adults include hypertension, diabetes, and smoking, as well as cardiac disease and sickle cell anemia; asymptomatic cerebrovascular disease and transient ischemic events may predict stroke in this age group. The investigation of a child with a stroke has traditionally focused on finding a single cause rather than looking for risk factors to which the patient may be exposed life long. Approximately half of children presenting with stroke have a known predisposing condition, but some have unexpected pathologies such as primary cerebrovascular disease associated with congenital heart anomalies, or may have modifiable risk factors such as hypertension associated with sickle cell disease. The literature on children presenting with initially unexplained (cryptogenic) stroke suggests that there is a daunting list of possible causes, but since the series have mainly been small, it has been difficult to evaluate the relative importance of the reported associations. This paper reviews the literature on congenital, genetic, and acquired risk factors for stroke in childhood, and includes data from the large series of patients seen at Great Ormond Street Hospital over the past 10 years. The majority have arteriographic abnormalities and there is little evidence for asymptomatic cardiac disease. Genetic predisposition, trauma, infection, and nutritional deficiencies appear to be important, although case-control studies will be required to prove causation. Appropriate screening for modifiable risk factors may lead to prevention of recurrence in some patients. In the long term, an understanding of the multiple etiologies of childhood cerebrovascular disease and ischemic stroke may lead to primary prevention in this age group, and perhaps in adults.

Brain Ischemia↗