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Biomedical subjects

S A Qureshi

Publications and source records attributed to S A Qureshi.

At least 19 recordsLinked to original sources

Use of the Amplatzer muscular ventricular septal defect occluder for closure of perimembranous ventricular septal defects.

BACKGROUND: Transcatheter closure of a perimembranous ventricular septal defect (PmVSD) is usually performed with an asymmetric Amplatzer occluder, which is not an ideal device. Experience with the use of the Amplatzer muscular ventricular septal defect occluder (MVSO) to close selected PmVSDs is presented. SETTING: Two tertiary referral centres for paediatric cardiology in two countries. OBJECTIVE: To look at the safety and efficacy of the application of the MVSO in patients with appropriate PmVSD anatomy. PATIENTS AND INTERVENTION: The procedure was performed in 10 patients aged 3.2-40 (mean 12.5) years. All had a PmVSD with a mean diameter of 5.4 (range 4-11) mm, with an extension towards the muscular septum. The mean distance of the defect from the aortic valve was 5.4 (range 4-6) mm. In all but one patient, the MVSO was introduced in routine antegrade transvenous fashion (4-mm device in one patient, 6-mm device in five, 8 mm in two, 10 mm in one, and 12 mm in one). In one patient, the device was deployed by retrograde implantation. RESULTS: All procedures except one were performed without complications, and complete closure of the VSD was achieved. One patient with a residual shunt developed haemolysis, which resolved over 10 days. In three patients, trivial, non-progressive tricuspid regurgitation appeared after the procedure. No other complications were observed over 1.7 (range 0.2-3.5) years of follow-up. CONCLUSION: Application of the MVSO for closure of selected PmVSDs seems to be a safe and effective treatment option.

Adolescent↗

Managed Care Network for the assessment of cardiac problems in children in a district general hospital: a working model.

AIM: To assess a model for cardiology assessments in children with suspected heart disease by a general paediatrician with special expertise in paediatric cardiology (PsePC) in a district general hospital. METHODS: A new monthly "screening" clinic was established in May 2004 by the PsePC to reduce the burden of new referrals on outreach tertiary paediatric cardiology services. All patients were to have echocardiograms as part of their referral for cardiac assessment. Over a one year period (May 2004-April 2005), through audit, details of referrers, indications for referral, echocardiography assessments, and subsequent management were recorded. This was compared with the pattern of patients seen in the joint paediatric cardiology outreach clinics over a two year period (May 2003-April 2005). RESULTS: In the "screening" clinic, there were 75 appointments for 65 patients seen in 12 months. Fifty five of these patients had normal echocardiographic studies. Of the 47 referrals with heart murmurs in asymptomatic children, four had structurally abnormal hearts on echocardiographic assessment. Between May-October 2003 and November 2003-April 2004, the number of new patients with normal echocardiographic studies seen in the paediatric cardiology outreach clinic was 33/106 (31%) and 28/110 (25.4%) respectively. Following the introduction of the "screening" clinic, the number decreased to 21/99 (21%) during May-October 2004, and 10/102 (9.8%) during November 2004-April 2005. CONCLUSION: This model can work effectively in order to identify pathology requiring input of a paediatric cardiologist more appropriately. Paediatricians with specific training in paediatric cardiology are potentially well equipped to provide this basic screening service.

Cardiology Service, Hospital↗

Three- and four-dimensional reconstruction of intra-cardiac anatomy from two-dimensional magnetic resonance images.

The present study was designed to evaluate the feasibility and clinical usefulness of three-dimensional (3D) reconstruction of intra-cardiac anatomy from a series of two-dimensional (2D) MR images using commercially available software. Sixteen patients (eight with structurally normal hearts but due to have catheter radio-frequency ablation of atrial tachyarrhythmias and eight with atrial septal defects (ASD) due for trans-catheter closure) and two volunteers were imaged at 1T. For each patient, a series of ECG-triggered images (5 mm thick slices, 2-3 mm apart) were acquired during breath holding. Depending on image quality, T1- or T2-weighted spin-echo images or gradient-echo cine images were used. The 3D reconstruction was performed off-line: the blood pools within cardiac chambers and great vessels were semi-automatically segmented, their outer surface was extracted using a marching cube algorithm and rendered. Intra- and inter-observer variability, effect of breath-hold position and differences between pulse sequences were assessed by imaging a volunteer. The 3D reconstructions were assessed by three cardiologists and compared with the 2D MR images and with 2D and 3D trans-esophagal and intra-cardiac echocardiography obtained during interventions. In every case, an anatomically detailed 3D volume was obtained. In the two patients where a 3 mm interval between slices was used, the resolution was not as good but it was still possible to visualize all the major anatomical structures. Spin-echo images lead to reconstructions more detailed than those obtained from gradient-echo images. However, gradient-echo images are easier to segment due to their greater contrast. Furthermore, because images were acquired at least at ten points in the cardiac cycles for every slice it was possible to reconstruct a cine loop and, for example, to visualize the evolution of the size and margins of the ASD during the cardiac cycle. 3D reconstruction proved to be an effective way to assess the relationship between the different parts of the cardiac anatomy. The technique was useful in planning interventions in these patients.

Arrhythmias, Cardiac↗

The efficacy and safety of stent redilatation in congenital heart disease.

OBJECTIVES: To assess the extent of neointimal proliferation and the safety and efficacy of stent redilatation in patients with stents implanted for aortic coarctation or branch pulmonary artery stenosis. DESIGN: Retrospective observational study. SETTING: Tertiary referral centre. PATIENTS AND INTERVENTIONS: Of 60 patients with Palmaz stents, 12 with coarctation and 12 with branch pulmonary artery stenosis (with 21 stented sites) underwent recatheterisation and stent redilatation. RESULTS: Neointimal thickening > 1 mm was detected in six of the 12 coarctation stents and at nine of the 21 stented sites in branch pulmonary arteries (five of which had been overdilated at implantation). Eight of the coarctation stents were electively underdilated at implantation. Coarctation stent redilatation increased median (range) lumen diameter from 9.2 (6.3-11.1) mm to 11.7 (9.8-14.1) mm (p = 0.002), decreased gradient from 10.5 (0-20) mm Hg to 0.5 (0-15) mm Hg (p = 0.008), and increased the ratio of stent diameter to descending aorta diameter from 0.66 (0.38-1.02) to 0.85 (0.52-1.2) (p = 0.008). Pulmonary artery stent redilatation increased lumen diameter from 6.9 (3.8-13.5) mm to 8.8 (4.8-14.1) mm (p < 0.001), decreased gradient from 24 (2-62) mm Hg to 12 (0-29) mm Hg (p < 0.001), and increased the ratio of stent diameter to diameter of distal pulmonary artery from 0.66 (0.44-1.5) to 0.86 (0.48-1.88) (p = 0.001). Dilatation of one peripheral pulmonary artery stent resulted in rupture of the vessel distal to the stent. CONCLUSIONS: Neointimal proliferation is precipitated by overdilating stents at implantation. Redilatation using balloons matched to distal vessel diameter increases stent lumen size, but may not optimise vessel diameter. Redilatation is effective whether the indication for redilatation is a resistant stenosis at implantation, underexpansion at implantation, neointimal proliferation, or relative stenosis caused by growth.

Adolescent↗

Hemodynamic response to continuous infusion of dobutamine in Alagille's syndrome.

BACKGROUND: Alagille's syndrome is a rare condition that is characterized by paucity of interlobular bile ducts and peripheral pulmonary artery stenosis. Liver transplantation in the setting of peripheral pulmonary stenosis and right ventricular hypertension seems to be associated with a higher mortality, which raises the concern that these patients are unable to increase their cardiac output in the immediate posttransplantation period to meet the demands of reperfusion and early graft dysfunction and cope with further increases in pulmonary vascular resistance. METHOD: Cardiac catheterization was performed in 15 children with Alagille's syndrome and peripheral pulmonary artery stenosis to measure the cardiac output response to dobutamine infusion. The cardiac output was measured before and during each increment of infusion of dobutamine at 10 microg/kg/min and 20 microg/kg/min by using a thermodilution catheter placed in the pulmonary artery. RESULTS: There was a significant change in the baseline cardiac index (P<0.001) with an infusion of 20 microg/kg/min of dobutamine with an increase from 4.4(1.0) L/min/m2 to 6.4(1.5) L/min/m2. There was, however, a wide variation between individuals in the increase in cardiac index, ranging from 7.3-95%. There was no correlation between the baseline systolic right ventricular/aortic pressure ratios and the increase in cardiac index (r=0.1086). CONCLUSION: The increase in cardiac index, in response to dobutamine in patients with Alagille's syndrome, is independent of the more conventional measurement of the right ventricular pressure. This method of producing a hemodynamic response is closer to the response that results after liver transplantation, and thus, it may be a better way of predicting the outcome of liver transplantation in these patients.

Adolescent↗

Stent implantation for superior vena cava occlusion after the Mustard operation.

A 25-year-old man who had undergone a Mustard repair for complete transposition of the great arteries 21 years previously developed complete occlusion of the superior vena cava and obstruction of the inferior vena cava. Transcatheter recanalization was performed using needle puncture of the superior obstruction followed by stent implantation into both systemic venous pathways with relief of obstructive symptoms.

Adult↗

Interventional and surgical management of aortic stenosis and coarctation.

Two patients, aged 42 and 44 years old, presented with the combination of aortic valve stenosis and coarctation. To avoid potential problems associated with one stage repair, both patients underwent successful endovascular stent implantation for coarctation followed within 2 weeks by aortic valve replacement using pulmonary autografts (Ross operation). Spiral thoracic computed tomographic scans were performed within 1 week of stent implantation to ensure the absence of aneurysm formation related to the stent before cardiopulmonary bypass.

Adult↗

Cause of high variability in drug dissolution testing and its impact on setting tolerances.

Considering a variable mixing/stirring and flow pattern in a drug dissolution vessel as a likely source of high variability in results, experiments were conducted using USP paddle apparatus by placing (aligned to the walls) a metal strip (1.7 mm thickx6.4 mm wide) in a dissolution vessel. The metal strip forces the undisintegrated tablet to settle about 3 mm away from the centre, facilitates spread of disintegrated material and diminishes the cone formation at the bottom of the vessel. To assess the impact of this altered environment in the vessel, but still maintaining the vessel dimensions within required specifications, drug release characteristics were evaluated for products having different formulation/manufacturing attributes. Tests were conducted with calibrator tablets (USP prednisone and salicylic acid tablets and FDA proposed NCDA No. 2 prednisone tablets) and two commercially available products (250 mg amoxicillin capsules and 5 mg glibenclamide tablets). Except for the glibenclamide tablet product, all products gave significantly (P<0.01) higher dissolution results with vessels containing metal strip than without. The extent of increased dissolution with the metal strip varied from product to product i.e. USP prednisone tablet was the smallest (14.4%) and NCDA No. 2 was the largest (88.4%). Based on the results obtained from this study, it is concluded that employing the current apparatuses, in many cases products will provide lower than anticipated results which may not be reflective of the product drug release characteristics. Test-to-test variability, within or between laboratories, can also be very high depending on the settling position of the product once dropped in the vessel and/or due to slight aberration in the walls of the vessel by altering the extent of spread of disintegrated material at the bottom of the vessel. Thus, dissolution testing will require wider tolerances to be useful for comparison of batch-to-batch or interlaboratory results.

Amoxicillin↗

Successful occlusion of a coronary arteriovenous fistula using an Amplatzer duct occluder.

In an 11-year old boy with a large coronary arteriovenous fistula between the left coronary artery and the right atrium, we achieved successful closure using a 10-8 Amplatzer Duct Occluder introduced from the right internal jugular vein. Angiography 6 weeks later showed complete occlusion of the fistula, with normal opacification of the left coronary arterial system. This technique may be used as an alternative to coils and surgery in selected patients.

Arteriovenous Fistula↗

Transcatheter coil occlusion of the arterial duct; results of the European Registry.

AIMS: To report on the data, collected by the Association for European Paediatric Cardiology (AEPC) Registry, on transcatheter coil occlusion of the arterial duct. METHODS AND RESULTS: A retrospective study was conducted of intention-to-treat data from 30 European and Middle Eastern tertiary referral centres which included an analysis of causes of suboptimal outcome. Since 1994, reports have been made on 1291 attempted coil occlusions of the arterial duct in 1258 patients. Median age at procedure was 4 years (range 0.1-52) and median weight was 29 kg (range 1.8-100). Following coil implantation, the immediate occlusion rate was 59%, which rose to 95% at 1 year. A suboptimal outcome occurred on 129 occasions (10% of procedures) and was defined as coil embolization, an abandoned procedure, persistent haemolysis, residual leak requiring a further procedure, flow impairment in adjacent structures and duct re-canalization. A number of clinical factors were chosen but only increasing duct size [odds ratio of 2.6:1 (CI 2-3.2)] and the presence of a tubular shaped duct [odds ratio 2.4:1 (CI 1.4-4)] were positively associated with an unfavourable outcome. CONCLUSION: The results of the European Registry support the view that transcatheter coil occlusion of the persistent arterial duct is a safe and effective procedure. Unfavourable outcomes are more likely when closing larger and/or tubular shaped ducts.

Adolescent↗

Catheter closure of coronary artery fistulas.

Coronary artery fistulas are rare and vary widely in their morphological appearance and presentation. This paper presents experience of catheter closure of coronary artery fistulas in 40 patients. Catheter closure was performed with a variety of techniques, including detachable balloons, stainless steel coils, controlled-release coils, controlled-release patent ductus arteriosus (PDA) coils, and Amplatzer PDA plug. The vast majority of the fistulas were occluded with coils and in particular, controlled-release coils. Successful occlusion of the fistula was achieved in 39 (97%) of 40 patients. In one patient, the detachable balloon deflated prematurely and the patient underwent elective surgery. One 4-month-old infant died approximately 6 hours after the procedure. Immediate occlusion of the coronary artery fistula occurred in 33 (82%) of patients and late occlusion in 4 patients. Thus overall, total occlusion was achieved in 37 (97%) of 39 patients. The main complication was embolization of the occlusion device, which occurred in 6 (17%) of cases. In one of these cases, a detachable balloon deflated prematurely, and in five patients, coils embolized and were retrieved. In one of the patients, all six coils embolized 24 hours after the procedure but were retrieved, and further coils were implanted successfully. Controlled-release coils have made an important contribution to the technique of catheter closure of coronary artery fistulas. Catheter closure of these fistulas is an acceptable alternative to the standard surgical treatment.

Cardiac Catheterization↗

Activation of insulin signal transduction pathway and anti-diabetic activity of small molecule insulin receptor activators.

We recently described the identification of a non-peptidyl fungal metabolite (l-783,281, compound 1), which induced activation of human insulin receptor (IR) tyrosine kinase and mediated insulin-like effects in cells, as well as decreased blood glucose levels in murine models of Type 2 diabetes (Zhang, B., Salituro, G., Szalkowski, D., Li, Z., Zhang, Y., Royo, I., Vilella, D., Diez, M. T. , Pelaez, F., Ruby, C., Kendall, R. L., Mao, X., Griffin, P., Calaycay, J., Zierath, J. R., Heck, J. V., Smith, R. G. & Moller, D. E. (1999) Science 284, 974-977). Here we report the characterization of an active analog (compound 2) with enhanced IR kinase activation potency and selectivity over related receptors (insulin-like growth factor I receptor, epidermal growth factor receptor, and platelet-derived growth factor receptor). The IR activators stimulated tyrosine kinase activity of partially purified native IR and recombinant IR tyrosine kinase domain. Administration of the IR activators to mice was associated with increased IR tyrosine kinase activity in liver. In vivo oral treatment with compound 2 resulted in significant glucose lowering in several rodent models of diabetes. In db/db mice, oral administration of compound 2 elicited significant correction of hyperglycemia. In a streptozotocin-induced diabetic mouse model, compound 2 potentiated the glucose-lowering effect of insulin. In normal rats, compound 2 improved oral glucose tolerance with significant reduction in insulin release following glucose challenge. A structurally related inactive analog (compound 3) was not effective on insulin receptor activation or glucose lowering in db/db mice. Thus, small molecule IR activators exert insulin mimetic and sensitizing effects in cells and in animal models of diabetes. These results have implications for the future development of new therapies for diabetes mellitus.

Animals↗