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Biomedical subjects

F A Chaudhry

Publications and source records attributed to F A Chaudhry.

At least 19 recordsLinked to original sources

Seasonal variation in bacterial pathogens isolated from stool samples in Karachi, Pakistan.

OBJECTIVE: To determine the seasonal variation of the commonly isolated bacterial pathogens in stool samples. MATERIAL AND METHODS: A retrospective descriptive study was undertaken of all the stool samples submitted from within Karachi to the Aga Khan University Hospital Laboratory over a period of five years (January 1997- December 2001) in order to determine the commonly isolated bacterial pathogens and to predict their seasonal variation. RESULTS: A total of 16379 stool samples were included in this review. Bacterial isolates were found in 6670 stool samples (culture detection rate=40.7%). The mean age at the time of culture of each sub-group was < or = 1 year group (6.58 +/- 3.1 months), 1-5 years (2.13 +/- 0.94 years), 5-14 years (8.3 +/- 2.6 yrs) and adults (43.2 +/- 18.5 years). Male: Female ratio was 1.2:1. Vibrio cholera 01 Ogawa (32.8%), Campylobacter jejuni (17.3%), Enteropathogenic Escherichia coli (9.9%), Salmonella paratyphi b (6.6%) and Shigella flexneri (6.2%) were the most common organisms isolated. These organisms show a distinct seasonal variation with summer predilection. CONCLUSION: In contrast to the previous studies from South Asia, which have identified E. coil, followed by Vibrio cholerae as the most common enteric isolates, we found Vibrio cholera 01 Ogawa followed by Campylobacter jejuni as the most common enteric pathogens isolated in an urban setting. It is important to consider seasonal variation when empirically treating diarrheal diseases in our region.

Adolescent↗

Coupled and uncoupled proton movement by amino acid transport system N.

The system N transporter SN1 has been proposed to mediate the efflux of glutamine from cells required to sustain the urea cycle and the glutamine-glutamate cycle that regenerates glutamate and gamma-aminobutyric acid (GABA) for synaptic release. We now show that SN1 also mediates an ionic conductance activated by glutamine, and this conductance is selective for H(+). Although SN1 couples amino acid uptake to H(+) exchange, the glutamine-gated H(+) conductance is not stoichiometrically coupled to transport. Protons thus permeate SN1 both coupled to and uncoupled from amino acid flux, providing novel mechanisms to regulate the transfer of glutamine between cells.

Amino Acid Transport Systems↗

Validation of transesophageal echocardiography to determine physiologic coronary flow.

UNLABELLED: Human studies have suggested that Doppler transesophageal echocardiography (TEE) can determine normal physiologic coronary blood flow (CBF) and alterations in CBF due to proximal flow-limiting stenoses. However, assessment of CBF by Doppler TEE has not been validated. To determine if true estimation of CBF could be obtained with Doppler TEE, seven mongrel dogs (weight range 28 kg-36 kg) were evaluated. Simultaneous CBF determinations by Doppler TEE and epicardial electromagnetic flow (EMF) and/or epicardial Doppler flow (EDF) probes were compared. Measurements were obtained at baseline and following varying degrees of proximal coronary occlusion, which produced reactive hyperemia. RESULTS: Consistent Doppler flow waveforms were obtainable by Doppler TEE in 34 different measurements during perturbations: Mean for TEE Flow (ml/min) = 85, EMF or EDF Flow (ml/min) = 53; Standard Deviation for TEE Flow (ml/min) = 45, EMF or EDF Flow (ml/min) = 38; Minimum for TEE Flow (ml/min) = 42, EMF or EDF Flow (ml/min) = 11; and Maximum for TEE Flow (ml/min) = 174, EMF or EDF Flow (ml/min) = 130. TEE Flow (ml/min) = 1.1 EMF/EDF flow + 26.3. There was a general trend towards overestimation of CBF by Doppler TEE. This study demonstrates that Doppler TEE is a promising method for obtaining measurements of CBF over the physiologic range.

Animals↗

Noninvasive characterization of stunned, hibernating, remodeled and nonviable myocardium in ischemic cardiomyopathy.

OBJECTIVES: We evaluated a novel protocol of dual-isotope, gated single-photon emission computed tomographic (SPECT) imaging combined with low and high dose dobutamine as a single test for the characterization of various types of altered myocardial dysfunction. BACKGROUND: Myocardial perfusion tomography and echocardiography have been used separately for the assessment of myocardial viability. However, it is possible to assess perfusion, function and contractile reserve using gated SPECT imaging. METHODS: We studied 54 patients with ischemic cardiomyopathy using rest and 4 h redistribution thallium-201 imaging and dobutamine technetium-99m sestamibi SPECT imaging. The sestamibi images were acquired 1 h after infusion of the maximal tolerated dose of dobutamine and again during infusion of dobutamine at a low dose to estimate contractile reserve. Myocardial segments were defined as hibernating, stunned, remodeled or scarred. RESULTS: Severe regional dysfunction was present in 584 (54%) of 1,080 segments. Based on the combination of function and perfusion characteristics in these 584 segments, 24% (n = 140) were labeled as hibernating; 23% (n = 136) as stunned; 30% (n = 177) as remodeled; and 22% (n = 131) as scarred. Contractile reserve, represented by improvement in wall motion/thickening by low dose dobutamine, was observed in 83% of stunned, 59% of hibernating, 35% of remodeled and 13% of scarred myocardial segments (p<0.05). CONCLUSIONS: It is possible with this new imaging technique to characterize dysfunctional myocardium as stunned, hibernating, remodeled and nonviable. These subtypes often coexist in the same patient.

Aged↗

Amino acid transport system A resembles system N in sequence but differs in mechanism.

Classical amino acid transport System A accounts for most of the Na(+)-dependent neutral amino acid uptake by mammalian cells. System A has also provided a paradigm for short- and long-term regulation by physiological stimuli. We now report the isolation of a cDNA encoding System A that shows close similarity to the recently identified System N transporter (SN1). The System A transporter (SA1) and SN1 share many functional characteristics, including a marked sensitivity to low pH, but, unlike SN1, SA1 does not mediate proton exchange. Transport mediated by SA1 is also electrogenic. Amino acid transport Systems A and N thus appear closely related in function as well as structure, but exhibit important differences in ionic coupling.

Amino Acid Sequence↗

Protein phosphatase-1 regulation in the induction of long-term potentiation: heterogeneous molecular mechanisms.

Protein phosphatase inhibitor-1 (I-1) has been proposed as a regulatory element in the signal transduction cascade that couples postsynaptic calcium influx to long-term changes in synaptic strength. We have evaluated this model using mice lacking I-1. Recordings made in slices prepared from mutant animals and also in anesthetized mutant animals indicated that long-term potentiation (LTP) is deficient at perforant path-dentate granule cell synapses. In vitro, this deficit was restricted to synapses of the lateral perforant path. LTP at Schaffer collateral-CA1 pyramidal cell synapses remained normal. Thus, protein phosphatase-1-mediated regulation of NMDA receptor-dependent synaptic plasticity involves heterogeneous molecular mechanisms, in both different dendritic subregions and different neuronal subtypes. Examination of the performance of I-1 mutants in spatial learning tests indicated that intact LTP at lateral perforant path-granule cell synapses is either redundant or is not involved in this form of learning.

Animals↗

Left ventricular apical thrombus and myocardial viability: a dobutamine stress echocardiographic study.

The objective of this article was to determine whether the presence of left ventricular apical thrombus is a marker of nonviable myocardium. Reduced coronary blood flow secondary to atherosclerosis may result in chronic reversible left ventricular wall-motion abnormalities. Severe regional abnormalities also predispose to formation of left ventricular thrombus. The relationship between left ventricular apical thrombus and myocardial viability has not been previously described. Eighty patients with coronary artery disease and chronic left ventricular dysfunction were studied by dobutamine stress echocardiography. Left ventricular apical thrombus was identified using echocardiographic criteria. Wall-motion analysis was performed using a standard 16-segment model and ejection fraction was calculated. As a result, 48 patients (60%) had definite or highly suspicious findings for left ventricular thrombus (group 1), and 32 patients (40%) had no thrombus (group 2). Group 1 had significantly higher composite (54.0 +/- 5.8 vs 43.3 +/- 6.4) and apical (6.0 +/- 2.7 vs 12.4 +/- 3.4) wall-motion scores compared to those in group 2 (P = 0.01). Thirty-two patients (67%) in group 1 demonstrated no contractile reserve in the apical segments, consistent with lack of viability, versus eight patients (25%) in group 2 (P = 0.0003). The number of viable apical segments per patient was significantly less in group 1 (0.7 +/- 1.2) versus group 2 (1.8 +/- 1.3) (P = 0.01). Left ventricular apical thrombus is more likely to be present when there is absence of myocardial viability in the corresponding segments.

Adult↗

Prognostic implications of myocardial contractile reserve in patients with ischemic cardiomyopathy.

The extent and degree of myocardial viability is an important parameter in the risk stratification of patients with significant left ventricular dysfunction due to coronary artery disease (CAD). Although several imaging modalities can identify viable myocardium, dobutamine stress echocardiography has gained considerable importance as an accurate, safe, and reliable method. In patients with significant left ventricular dysfunction secondary to CAD, identifying the presence and extent of contractile reserve and, therefore, viable myocardium, during low dose dobutamine infusion can predict recovery of left ventricular function postrevascularization, survival, and future cardiac events.

Cardiotonic Agents↗

Enhanced detection of ischemic myocardium by transesophageal dobutamine stress echocardiography: comparison with simultaneous transthoracic echocardiography.

The diagnostic accuracy of dobutamine stress echocardiography is limited in patients with poor transthoracic acoustic windows. Transesophageal echocardiography (TEE) overcomes these limitations and thus may increase the clinical usefulness of dobutamine stress echocardiography. The present study was designed to compare the diagnostic accuracies of transesophageal and transthoracic dobutamine stress echocardiography for the identification of coronary artery disease (CAD) in a cohort of patients with a higher incidence of poor acoustic windows. Forty-two male patients (mean age, 66 +/- 9 years) underwent dobutamine stress echocardiography with simultaneous transesophageal and transthoracic imaging. Coronary arteriography was performed in 28 patients (67%). Transesophageal imaging adequately visualized 99.6% of left ventricular segments compared with 76.2% visualized by transthoracic imaging (P < 0.0001). There was substantial agreement between the two techniques for segmental wall motion analysis at baseline (kappa 0.76; 95% CI, 0.70-0.82); however, at peak dobutamine dose, agreement was significantly reduced (kappa 0.62; 95% CI, 0.55-0.69). The sensitivity (88% vs 75%), specificity (100% vs 75%), and positive predictive value (100% vs 80%) for the identification of CAD were all superior for transesophageal imaging. Transesophageal imaging correctly identified 11 of the 12 patients (92%) with multivessel disease compared with 5 patients (42%) identified by transthoracic imaging (P < 0.03). There were no major complications. Transesophageal dobutamine stress echocardiography is a safe, feasible, and accurate technique for the identification and risk stratification of patients with CAD. Transesophageal imaging appears to be superior to transthoracic imaging for identifying both the presence and extent of CAD, specifically in patients with poor acoustic windows.

Aged↗

Reversible left ventricular dysfunction.

The extent and degree of myocardial viability are important parameters in the risk stratification of patients with significant left ventricular dysfunction secondary to coronary artery disease. Although several imaging modalities can identify viable myocardium, dobutamine stress echocardiography has gained considerable importance as an accurate, safe, and reliable method. In patients with significant left ventricular dysfunction secondary to coronary artery disease, identification of the presence and extent of contractile reserve and, therefore, viable myocardium during low-dose dobutamine infusion can predict the recovery of left ventricular function after revascularization, survival rate, and future cardiac events.

Contrast Media↗

The role of stress echocardiography in children.

Exercise and pharmacological stress echocardiography are well-accepted techniques of evaluating coronary artery disease in adults. In children, however, experience with stress echocardiography is limited and continues to evolve. The objective of this focused review was to describe the experience with exercise and dobutamine stress echocardiography in the pediatric population, with an emphasis on technique, current indications, and future directions. Experience is reported in children with prior Kawasaki disease or heart transplant recipients, as well as patients with congenital coronary abnormalities. In addition, stress echocardiography has been used in patients who have undergone coronary artery bypass graft surgery to evaluate short- and long-term graft patterning. Stress echocardiography appears to be a feasible, safe, and useful modality for the noninvasive assessment of flow-limiting stenosis in the pediatric population and can be used serially in the routine follow-up and risk stratification in children at risk for coronary events.

Child↗

Molecular analysis of system N suggests novel physiological roles in nitrogen metabolism and synaptic transmission.

The amino acid glutamine has a central role in nitrogen metabolism. Although the molecular mechanisms responsible for its transport across cell membranes remain poorly understood, classical amino acid transport system N appears particularly important. Using intracellular pH measurements, we have now identified an orphan protein related to a vesicular neurotransmitter transporter as system N. Functional analysis shows that this protein (SN1) involves H+ exchange as well as Na+ cotransport and, under physiological conditions, mediates glutamine efflux as well as uptake. Together with the pattern of SN1 expression, these unusual properties suggest novel physiological roles for system N in nitrogen metabolism and synaptic transmission.

Amino Acid Sequence↗

Comparison of dobutamine echocardiography, dobutamine sestamibi, and rest-redistribution thallium-201 single-photon emission computed tomography for determining contractile reserve and myocardial ischemia in ischemic cardiomyopathy.

Both dobutamine stress echocardiography (DSE) and myocardial perfusion scintigraphy are used to assess myocardial viability. Few studies have compared the data on myocardial viability and ischemia by low and peak dose DSE and myocardial perfusion imaging in the same patients. Fifty-four patients (45 men and 9 women aged 65 +/- 9 years) with ischemic cardiomyopathy (mean ejection fraction 24 +/- 9%) underwent rest 4-hour redistribution thallium-201 single-photon emission computed tomography (SPECT), low and peak dose DSE, and dobutamine sestamibi SPECT. A total of 864 segments were analyzed (16 segments/patient). Wall motion abnormality was present in 796 segments (92%), and contractile reserve during dobutamine infusion was seen in 400 of these segments (50%). Contractile reserve was seen in 331 of 509 hypokinetic segments (65%) and 69 of 287 akinetic/dyskinetic segments (24%) (p <0.001). Contractile reserve was more frequent in segments with normal thallium uptake (64%), reversible thallium defects (42%), or mild to moderate fixed thallium defects (48%) than severely fixed defects (22%) (p <0.05 each). Concordant information about viability by thallium imaging and DSE was obtained in 62% of segments. Dobutamine sestamibi ischemia was seen in 518 of 796 segments (65%) compared with 265 segments (33%) by DSE (p <0.001). Scintigraphic ischemia was noted in 126 of 195 segments (65%) demonstrating biphasic response, 129 of 205 segments (63%) showing sustained improvement, 42 of 70 segments (60%) deteriorating during dobutamine infusion, and 221 of 326 (68%) demonstrating no change (p = NS). Thus, in patients with ischemic cardiomyopathy, contractile reserve is more frequent in hypokinetic segments than akinetic/dyskinetic segments. The number of segments with normal or near-normal thallium uptake or with scintigraphic ischemia is significantly greater than the number of those capable of increasing contractile function or demonstrating an ischemic response during dobutamine echocardiography.

Adult↗

Narrowing of the superior vena cava-right atrium junction during radiofrequency catheter ablation for inappropriate sinus tachycardia: analysis with intracardiac echocardiography.

OBJECTIVES: The study explored the potential for tissue swelling and venous occlusion during radiofrequency (RF) catheter ablation procedures using intracardiac echocardiography (ICE). BACKGROUND: Transient superior vena cava occlusion has been reported following catheter ablation procedures for inappropriate sinus tachycardia (IST). Presumably, venous occlusion could occur owing to thrombus formation or tissue swelling with resultant narrowing of the superior vena cava-right atrial (SVC-RA) junction. METHODS: Intracardiac echocardiography (9 MHz) was used to guide ablation catheter position and for continuous monitoring during RF application in 13 ablation procedures in 10 patients with IST. The SVC-RA junction was measured prior to and following ablation. Successful ablation was marked by abrupt reduction in the sinus rate and a change to a superiorly directed p-wave axis. RESULTS: Eleven of 13 procedures were successful, requiring 29 +/- 20 RF lesions. Prior to the delivery of RF lesions, the SVC-RA junction measured 16.4 +/- 2.9 mm. With RF delivery, local and circumferential swelling was observed, causing progressive reduction in the diameter of the SVC-RA junction to 12.6 +/- 3.3 mm (24% reduction, p = 0.0001). A reduction in SVC-RA orifice diameter of > or = 30% compared to baseline was observed in five patients. CONCLUSIONS: The delivery of multiple RF ablation lesions, often necessary for cure of IST, can cause considerable atrial swelling and resultant narrowing of the SVC-RA junction. Smaller venous structures, such as the coronary sinus and the pulmonary veins, would also be expected to be vulnerable to this complication. Thus, ICE imaging may be helpful in preventing excessive tissue swelling leading to venous occlusion during catheter ablation procedures.

Adult↗

Prognostic implications of myocardial contractile reserve in patients with coronary artery disease and left ventricular dysfunction.

OBJECTIVES: This study was performed to assess the prognostic implications of myocardial contractile reserve (MCR) in patients with coronary artery disease (CAD) and left ventricular (LV) dysfunction. BACKGROUND: MCR during dobutamine stress echocardiography (DSE) identifies viable myocardium that may improve in function after revascularization. Whether revascularization influences prognosis of patients with MCR has not been determined. METHODS: We performed DSE in 80 patients with CAD and LV dysfunction (ejection fraction < or =40%). Viable myocardium was defined in dysfunctional myocardial segments as enhanced thickening and contraction during low-dose dobutamine (5 to 10 mcg/kg/min). Serial prospective follow-up was obtained in all patients (mean follow-up 2.2 +/- 1.1 years). RESULTS: Among 52 patients treated medically, there were 20 cardiac deaths. By multivariate analysis, the number of dysfunctional segments demonstrating MCR was the strongest predictor of survival (p < 0.03). Patients with MCR had better initial survival during medical therapy than did those without MCR, but this survival advantage was not maintained beyond three years. In contrast, survival was excellent in patients with MCR who underwent myocardial revascularization. Among 58 patients with MCR in > or =5 myocardial segments, survival at three years was 93 +/- 6% in the 24 patients who were revascularized but only 49 +/- 15% in the 34 treated medically (p < 0.02). CONCLUSIONS: Myocardial contractile reserve is a significant predictor of survival in patients with CAD and LV dysfunction undergoing medical therapy. Although patients with MCR have an initial survival advantage, this advantage is lost over the course of three years. In contrast, survival in patients with significant MCR is enhanced by revascularization.

Adult↗

Dobutamine stress echocardiography: experience in pediatric heart transplant recipients.

BACKGROUND: Transplant coronary arteriopathy causes late death and is difficult to detect noninvasively. Dobutamine stress echocardiography is being used for risk stratification in adult recipients at some transplant centers, thus we investigated its role in a pediatric population. METHODS: We performed 46 stress echo studies (mean age = 11.8 years; mean years post transplantation = 4.3). An atropine/dobutamine protocol (5-40 mcg/kg/min) was used to attain a predicted target heart rate. Serial echocardiographic images were acquired at baseline and at each increment of dobutamine and recovery, and were digitized online. Data were correlated with endomyocardial biopsy (n = 23), coronary angiography (n = 26) or autopsy (n = 6). All studies were well tolerated. RESULTS: Target heart rate was achieved in 41/46 (89%) studies. The mean heart rate significantly increased from 95 to 169 beats/min and mean systolic blood pressure from 123 to 153 mm Hg (p<.05). The mean peak pressure-rate product was 23,041 beats-mm Hg/min. Coronary arteriopathy was confirmed in 5 patients by angiography (n = 3) explanted heart (n = 1) or autopsy (n = 4). In this group, abnormalities included a new reversible wall motion abnormality (n = 2), left ventricular cavity dilation with stress (n = 3), ischemia (n = 2), increased mitral insufficiency (n = 1) and marked diastolic dysfunction (n = 1). A positive study predicted death or graft failure (p< .0005). CONCLUSIONS: Echocardiographic abnormalities during stress correlated with coronary arteriopathy in this small cohort of patients; however, larger multi-center studies are warranted to assess the utility of dobutamine stress echocardiography for risk stratification for coronary disease in pediatric transplant recipients.

Adolescent↗

Imaging technique and clinical utility for electrophysiologic procedures of lower frequency (9 MHz) intracardiac echocardiography.

Intracardiac echocardiography using a new 9-MHz ultrasound catheter was performed in 30 patients undergoing percutaneous catheter mapping and radiofrequency ablation of a tachyarrhythmia, because the imaging capabilities with this intracardiac echocardiographic catheter permit detailed identification of normal and abnormal cardiac anatomy with improved imaging depth. Intracardiac echocardiography is of significant clinical utility during ablation for guiding interatrial septal puncture, assessing placement and contact of mapping/ablation catheters, monitoring ablation lesion morphologic changes, and diagnosing procedure-related complications.

Adult↗