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Biomedical subjects

J Tharakan

Publications and source records attributed to J Tharakan.

At least 19 recordsLinked to original sources

Computed tomography perfusion of ischaemic stroke patients in a rural Malaysian tertiary referral centre.

INTRODUCTION: Computed tomography (CT) perfusion is a new method to diagnose ischaemic stroke especially in developing countries. It identifies the area and is useful to predict the size of final infarction. The aim of this study was to assess cerebral ischaemia with CT perfusion (CTP) among patients with acute ischaemic stroke in Hospital Universiti Sains Malaysia, a tertiary referral centre in a rural setting. METHODS: 42 consecutive unenhanced CT and CTP examinations of the brain in adult patients were evaluated prospectively. Unenhanced CT images were divided into normal, suspicious or frank infarction. CTP images was classified as normal or ischaemic. Subgroup analysis was carried out with a limit of six hours from time of ictus. RESULTS: Out of 42 patients, 20 had frank infarction on unenhanced CT, 15 had suspicious CT studies, while seven were normal. There was no significant association of demographical, clinical and radiological parameters to CTP in the whole group among acute stroke patients without frank infarction. Among the subgroup of patients without frank infarction, there was no significant association between unenhanced CT and CTP in patients who were studied less than six hours after stroke (p-value is 0.063) as well as those after six hours (p-value is 0.317). The prevalence of a normal unenhanced CT and positive CTP for ischaemia was 22.7 percent (95 percent confidence interval 7.8, 45.4). CONCLUSION: CTP may be a useful imaging tool for determining cerebral infarction in a rural-based community population, especially in cases where the unenhanced CT is normal. Thrombolysis is a therapeutic option, even when the history of onset of stroke is unclear.

Acute Disease↗

The sympathetic skin response in carpal tunnel syndrome.

The sympathetic skin response (SSR) is an evoked change in electrical skin potential and is an index of the function of sympathetic pathways. We studied the SSR evoked by electrical stimulation of the median nerve and recording from the contralateral hands in 30 patients with carpal tunnel syndrome (CTS) without clinical autonomic signs and compared the results to the SSR in 30 normal controls. The SSR was absent in the affected hands in seven (23%) patients. In the other carpal tunnel syndrome patients (77%), a significant reduction in the SSR area was seen in the records from the affected hands. Subclinical sympathetic nerve fibre involvement occurs in the affected median nerves in CTS.

Adult↗

Central pulmonary artery anatomy in right ventricular outflow tract obstructions.

We reviewed the cine-angiograms of 190 patients with right ventricular outflow tract (RVOT) obstructions for size and anatomy of pulmonary arteries, patent ductus arteriosus (PDA) and major aorto pulmonary collateral arteries (MAPCAs). Patients were grouped into three, Tetralogy of Fallot (TOF) with pulmonary atresia (group 1, N=86), TOF with pulmonary stenosis (group 2, N=97) and 7 cases of pulmonary atresia with intact interventricular septum (group 3). Out of 86 patients in group 1, 49 had PDA alone, 30 had MAPCAs alone, six had both and one had none. In group 2, 31 patients had persistent PDA and one patient had MAPCAS and PDA. A discrete stenosis (DS) of pulmonary artery was seen significantly more in patients with RVOT obstructions associated with PDA compared to patients without PDA (67/84 vs. 5/96). Out of the 84 cases with ducti, 53 had stenosis of the pulmonary artery at the site of ductus insertion. Thus presence of PDA was an important factor in the development of DS. The likely cause of pulmonary artery stenosis in TOF with PDA may be the opposing flows through RVOT and PDA producing a watershed effect at the ductus-pulmonary artery junction. Diffuse hypoplasia of pulmonary arteries (DH) was seen more significantly in RVOT obstructions associated with MAPCAs, compared to other patient groups (19/36 vs. 14/87). These small pulmonary arteries had no discrete stenosis and this diffuse hypoplasia might be the result of inadequate blood flow during intrauterine life [Harikrishnan S, Tharakan J, Titus T, Bhat A, Sivasankaran S, Bimal F, Syam Sunder KR, James, KJ. Central pulmonary artery anatomy in right ventricular outflow tract obstructions. Indian Heart Journal 1997;49:624 (Abstract)[18]].

Cineangiography↗

Macromolecular aspartate aminotransferase.

Macroenzymes are serum enzymes that have a greater molecular mass than the corresponding enzyme normally found in serum (Klonoff. West J Med 1980; 133: 392-407). Serum AST (aspartate aminotransferase) has rarely been reported to complex with immunoglobulins, resulting in an elevation in serum AST activity. Physicians should be aware of this condition so that patients are not subjected to invasive and costly procedures unnecessarily (Litin et al. Mayo Clin Proc 1987; 62: 681-687). We report on such a patient with a raised AST due to macroenzyme formation.

Adult↗

Malignant hepatic tumours associated with previous exposure to Thorotrast: four cases.

This report concerns four patients in a district general hospital who died from malignant liver tumours associated with Thorotrast (thorium dioxide) deposits in the liver. Three were known to have had diagnostic angiographic studies performed 36 to 43 years previously using Thorotrast as the contrast agent. In the fourth case no previous relevant information could be obtained. There were two men and one woman with hepatocellular carcinoma and one woman with cholangiocarcinoma. In one of the hepatoma cases there was associated hypercalcaemia of malignancy. Reported latency intervals suggest that cases of Thorotrast-related hepatic malignancy may present up to the second decade of the twenty-first century.

Aged↗

Clinical profile and natural history of Ebstein's anomaly of tricuspid valve.

There were 63 patients of Ebstein's anomaly of tricuspid valve encountered from 1976 to 1991; 28 (44.4%) were male and 35 (55.6%) female. Their age at presentation ranged from 3 months to 51 years. Five (7.9%) patients were asymptomatic, 48 (76.2%) had class II-III exertional dyspnoea, palpitation or both. Thirty patients (47.6%) had cyanosis. Electrocardiogram showed paroxysmal atrial fibrillation in two, chronic atrial fibrillation in four (6.3%), paroxysmal supraventricular tachycardia in seven, atrial or ventricular ectopic beats in five (7.9%), 2:1 atrioventricular block in one (1.6%), complete atrioventricular block in two (3.2%) and type B WPW syndrome in nine patients (14.3%). Chest X-ray showed diminished vascularity in 22 (34.9%). Diagnosis was established by cardiac catheterization and or echocardiography. Atrialized right ventricular chamber was demonstrated in 51 (80.9%) by angiography and in 40 (63.5%) by electrophysiology. Patients were followed up for 1-172 months. Seventeen patients (26.9%) required surgery. Three patients (4.8%) died during medical follow-up, and five (7.9%) died following surgery. Survival probability for 46 medical patients was 88.9% at 172 months. Factors affecting survival were pulmonary blood flow, cyanosis, clubbing and systemic arterial oxygen saturation.

Adolescent↗

Prognosis for patients with Eisenmenger syndrome of various aetiology.

The objective of this study was to determine the long-term survival pattern and variables affecting long-term survival and complications occurring during follow-up of patients with Eisenmenger syndrome. A retrospective study of patients diagnosed with Eisenmenger syndrome were followed up. A tertiary care centre was used and it provided superspeciality services in various disciplines. The subjects included 201 patients with Eisenmenger syndrome--diagnosed by a combination of echocardiography and a peripheral arterial oxygen saturation study and/or cardiac catheterisation with or without angiocardiography--worked up and followed up for variable duration over a period of 16 years from 1976 to 1992. One hundred nine patients were females and 92 were males--age of presentation varied from 3 months to 62 years (mean +/- standard deviation 19.23 +/- 12.62 years). A total of 12 different anatomic lesions were seen--the most common three being ventricular septal defect (33.33%), aterial septal defect (29.85%), and patent ductus arteriosus (14.23%). History, physical examination, chest skiagram and electrocardiogram established only the presence of pulmonary arterial hypertension except where differential cyanosis indicating ductus was discernible or the degree of splitting of second heart sound provided some clue to the level of shunt. Contrast echocardiography, completed in 25.4% established the level of shunt in all patients. In others the diagnosis was confirmed by cardiac catheterisation. Twenty patients died during a mean follow-up period of 54.6 +/- 54.47 months. Sudden cardiac deaths (30%), congestive heart failure (25%) and haemoptysis (15%) were the most predominant causes of death. Only one patient died during puerperium.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Balloon pulmonary valvoplasty: factors determining short- and long-term results.

Balloon pulmonary valvoplasty was performed in 139 patients (age 2-44 years) with pulmonary valve stenosis. The right ventricular peak systolic pressure decreased from 137.1 +/- 46.8 mmHg to 76 +/- 51.3 mmHg (P < 0.001) and the right ventricle to pulmonary artery peak systolic gradient decreased from 116.3 +/- 49 mmHg to 54.4 +/- 51.9 mmHg (p < 0.001). There was no significant change in systemic artery systolic pressure. The right ventricular peak systolic pressure to systemic artery systolic pressure ratio decreased from 1.13 +/- 0.41 to 0.63 +/- 0.42 (P < 0.001). Patients with incomplete immediate relief of obstruction (right ventricle to pulmonary artery peak systolic gradient > 35 mmHg) had higher pre-dilatation right ventricular peak systolic pressure (161.1 +/- 45.3 mmHg vs. 93.9 +/- 38.8 mmHg, P < 0.001) and higher right ventricular peak systolic pressure to systemic artery systolic pressure ratio (1.31 +/- 0.42 vs 0.98 +/- 0.33, P < 0.001) pre-dilatation and were older (17.2 +/- 8.6 years vs. 12.8 +/- 9.7 years, P < 0.01). The residual right ventricle to pulmonary artery peak systolic gradients in the majority of patients were infundibular, which regressed at follow up even in patients who did not receive long-term oral beta blockers. Follow up catheterisation in 79 patients after 13 +/- 8.7 months showed a further fall in right ventricular peak systolic-pressure (P < 0.001) and right ventricle-to-pulmonary artery peak systolic gradient (P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Physical and biochemical characterization of five commercial resins for immunoaffinity purification of factor IX.

The American Red Cross has developed an immunoaffinity chromatography method to purify human coagulation factor IX (FIX) to homogeneity using monoclonal antibodies (MAb) that bind FIX in the presence of divalent cations. The MAb is immobilized on Sepharose CL2B, a soft gel with a low pressure tolerance as well as poor large-scale performance characteristics, including low reusability, and resin crumbling and deterioration. In this study, we examined several commercially available resin supports. Aside from Sepharose CL2B, we studied two other cross-linked agaroses, as well as two synthetic polymer supports. Immobilization chemistries included cyanogen bromide activation of agarose, 2-fluoro-2 methylpyridinium toluene-4-sulfonate activation of one of the synthetic polymer as well as aldehyde group reduction by NaCNBH3 to form secondary amine linkages on one of the cross-linked agaroses. To determine the feasibility of using the resins in large-scale immunoaffinity chromatographic purification of FIX, we studied physical and biochemical properties of the resins. The physical characteristics studied included the crushability of the resins under pressure as well as ability to support increasing flow-rates at increasing pressures. The biochemical examination of the various resins focused on efficiency of antigen capture by the immobilized antibody ligand and the effect of flow-rate on MAb efficiency, where we found that very low flow-rates slightly increased the capacity of the MAb. The results demonstrate a straightforward method of assessing the feasibility of using particular resins in large-scale affinity purification.

Antibodies, Monoclonal↗

Balloon angioplasty for native coarctation of the aorta in children and adults: factors determining the outcome.

Balloon angioplasty was performed in 46 patients (age 2-40 yr) with discrete native coarctation of aorta. Patients with associated patent ductus arteriosus, aberrant subclavian artery and aneurysms were excluded. The peak systolic gradient across the coarcted segment decreased from 52.1 +/- 18.5 mmHg to 18.6 +/- 14.8 mmHg (p less than 0.001), and the diameter of the coarcted segment increased from 3.6 +/- 1.7 mm/m2 to 9.1 +/- 3.2 mm/m2 (p less than 0.001). Follow-up haemodynamic and angiographic studies performed in 21 patients at 13.1 +/- 6.9 months after angioplasty, showed good results in 15 patients. Four patients undergoing haemodynamic study and 4 other patients undergoing noninvasive evaluation were graded as having bad results at follow-up. In 5 of these patients the poor results were due to primary failure of angioplasty in relieving the gradient, and three developed re-coarctation after initial fall in the trans-coarctation gradient. Four risk factors were identified on univariate analysis, which were associated with significantly larger residual gradients at follow-up: (1) size of isthmus/size of coarcted segment ratio less than 3.0; (2) size of post-coarctation descending aorta/size of isthmus ratio greater than 1.75; (3) size of coarcted segment after angioplasty/size of coarcted segment before angioplasty ratio less than 2.0; and (4) size of balloon/size of coarcted segment ratio less than 3.0. The presence of one or more risk factors was associated with bad late results. On multivariate analysis the ratio of balloon size/coarcted segment size was found to be the sole independent predictor of the late outcome (p less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Evaluation of CNBr, FMP and hydrazide resins for immunoaffinity purification of factor IX.

The American Red Cross has developed an immunoaffinity chromatography method to purify human coagulation Factor IX to high levels of purity for therapeutic treatment of hemophilia B. The resin currently used in this process is Sepharose CL2B, a cross-linked 2% agarose, which is activated with cyanogen bromide to immobilize an anti-Factor IX monoclonal antibody. This study evaluated two alternative resins and coupling chemistries, a synthetic polymer bead activated by 2-fluoro-1-methyl-pyridinium toluene 4-sulfonate (FMP) and a cross-linked 2% agarose bead with free hydrazide groups for site-specific coupling. The cyanogen bromide and FMP chemistries immobilize the monoclonal antibody in a random orientation. In hydrazide coupling, the monoclonal antibody is immobilized by the non-antigen-binding part of the molecule which, theoretically, should increase the amount of immobilized monoclonal antibody able to bind antigen. To examine this, the capacity of the resins to bind Factor IX and the purity and recovery of Factor IX eluted from the resins were measured. The FMP-activated resin exhibited the lowest capacity, binding only 2% of the Factor IX feed. Sepharose CL2B bound 87% of the loaded protein, while the hydrazide resin bound 43%. These results suggest that (a) hydrazide activation may be insufficient to orient monoclonal antibody and (b) other factors such as steric hindrances and diffusional resistances during immobilization may be important. Neither of the other resins tested demonstrated improved performance compared with cyanogen bromide-activated Sepharose CL2B for the immunoaffinity purification of Factor IX.

Antibodies, Monoclonal↗