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Biomedical subjects

M Akhtar

Publications and source records attributed to M Akhtar.

At least 127 records · Page 7Linked to original sources

Microwave applicator design for cardiac tissue ablations.

A variety of microwave applicators were designed, fabricated and tested for catheter applications: I-radiators, U-radiators, O-radiators, forward helical coil radiator, reverse helical coil, double coil radiator, loaded monopole radiator, leaky coaxial radiator and tee radiators. The comparative and relative radiation characteristics of these applicators were tested in a saline bath and tissues. Most radiators designed produced larger lesions than have been described previously.

Animals↗

Relative efficacy of different tilts with biphasic defibrillation in humans.

OBJECTIVE: The goal of this study was to assess if tilt bears any impact on defibrillation efficacy of biphasic shocks. BACKGROUND: Although it has been shown that biphasic waveform may increase the defibrillation efficacy, this pulsing method has not been as extensively studied in patients, and information regarding the effect of different tilts is lacking. METHODS: This study consisted of two similar but distinct protocols including 33 patients undergoing transvenous defibrillator implant. In 17 patients (Part I) defibrillation threshold was obtained delivering biphasic waveforms with 50%, 65%, and 80% tilt in random fashion. Similarly, in 16 patients (Part II) testing of biphasic waveform with 40%, 50%, and 65% tilt was performed in random order. The electrode system used consisted of two transvenous leads and a subcutaneous patch in all 33 patients. RESULTS: In Part I, tilt of 50% demonstrated a defibrillation threshold significantly lower than 65% tilt (7.5 +/- 4.3 J vs 9.7 +/- 5.0 J; P = 0.04) and 80% tilt (7.5 +/- 4.3 J vs 11.7 +/- 5.9 J; P < 0.01). Similarly, 65% tilt provided a lower defibrillation threshold than 80% tilt (9.7 +/- 5.0 J vs 11.7 +/- 5.9 J; P = 0.02). In Part II, no significant difference was observed in terms of defibrillation threshold between 40% tilt and the two tilts of 50% and 65%. However, as in Part I, 50% tilt provided a significant reduction of the energy to defibrillate as compared to 65% tilt (6.3 +/- 3.6 J vs 9.0 +/- 4.8 J; P < 0.01). The 50% tilt resulted in better defibrillation efficacy than 65% tilt independent of the lead system used for testing (Medtronic Transvene and CPI Endotak-C). CONCLUSIONS: Biphasic shocks with 50% tilt required less energy for defibrillation than 40%, 65%, and 80% tilts. However, in the clinical setting a programmable tilt may be preferable to account for some patient-to-patient variability.

Adult↗

Response to beta blockers in patients with neurocardiogenic syncope: how to predict beneficial effects.

UNLABELLED: No definitive data are available about the possibility of predicting improvement in patients with neurocardiogenic syncope treated with beta blockers. Among 112 patients with syncope and a positive head-up tilt test (HUT), independent predictors for prevention of symptoms with beta blockers were determined using the Cox proportional hazards model. Each patient underwent HUT at 70 degrees for 20 minutes both in the drug-free state and during isoproterenol infusion given to increase the heart rate by at least 25%. Fifty-nine patients had a positive HUT during isoproterenol infusion and 53 in the drug-free state. All patients were then given esmolol infusion at 500 micrograms/kg per minute for 3 minutes followed by 300 micrograms/kg per minute maintenance dose. HUT was then repeated as previously described with or without isoproterenol, depending upon the initial positive response. Regardless of the response during esmolol, all patients were treated with metoprolol 50 to 100 mg twice daily. At follow-up, 36 patients experienced symptom relapse. Four of them had negative HUT on esmolol, whereas the remaining 32 did not respond to the acute infusion of esmolol. Only four patients with positive HUT on esmolol had a favorable response to metoprolol. Patients responding to metoprolol were older (55 +/- 12 years vs 42 +/- 15 years, P < 0.05). Response to metoprolol was predicted by a negative test on esmolol (P < 0.0001) and a positive HUT on isoproterenol (P < 0.001). Age older than 42 years was also associated with a higher likelihood of metoprolol success (P < 0.02). CONCLUSION: Acute challenge with esmolol infusion appears to be an accurate predictor of response to chronic beta blockers, together with age and a positive HUT during low-dose isoproterenol infusion.

Adrenergic beta-Agonists↗

Functional bundle branch block as a delayed manifestation of retrograde concealment in the His-Purkinje system.

INTRODUCTION: The mechanism of functional bundle branch block induced at the onset of supraventricular tachycardia (SVT) is well established. However, no data exist to address the underlying mechanism of functional bundle branch block occurring in the second beat of SVT, when the first beat is conducted with a narrow QRS morphology and preceded by ventricular stimulation. METHODS AND RESULTS: Two patients showing such a phenomenon form the basis of this report. Patient 1 with AV nodal reentrant tachycardia of the common variety persistently demonstrated functional right bundle branch block in the second SVT complex when a short train of ventricular pacing was introduced during SVT. This occurred without any discernible change in the SVT cycle length. Patient 2 had a manifest posteroseptal accessory pathway and inducible orthodromic reentrant tachycardia. Functional bundle branch block during propagation of the second SVT complex invariably occurred either in the left bundle when SVT was induced by a bundle branch reentrant complex during premature ventricular stimulation, or in the right bundle when SVT was induced with a short train of ventricular pacing. The development of functional bundle branch block was preceded by minimal or no cycle length variations in the His-bundle inputs. CONCLUSION: These observations suggest that the type of functional bundle branch block occurring in the second SVT complex as a de novo phenomenon may be related to the relative timing of the retrograde penetration of the right versus left bundle during ventricular pacing or bundle branch reentrant complex. Therefore, due to its longest cycle length of activation and refractoriness, the earliest site of retrograde penetration is the most likely site of functional block during propagation of the second SVT complex. This delayed manifestation of retrograde concealment may provide new information regarding the electrophysiologic behavior of the His-Purkinje system.

Adolescent↗

Facilitation of sustained bundle branch reentry by atrial fibrillation.

An electrophysiologic evaluation was performed in a patient with an idiopathic dilated cardiomyopathy and syncope. Ventricular tachycardia was not inducible despite the use of a variety of pacing maneuvers during sinus rhythm. Only after the electrical induction of atrial fibrillation did sustained bundle branch reentrant tachycardia (with both right and left bundle branch block QRS configurations) spontaneously occur and become reproducibly induced during right ventricular pacing. Ablation of the right bundle branch eliminated reproducibility of the tachycardia.

Aged↗

Therapy of ventricular tachycardia in patients with nonischemic cardiomyopathies.

In patients with IDCM and sustained VT, every effort should be made to exclude bundle branch reentrant tachycardia. We strongly believe that this mechanism of VT remains underdiagnosed despite electrophysiologic evaluation. In appropriate candidates with cardiomyopathies and "nonbundle branch reentrant VT," ICD implantation is frequently the treatment of choice, especially if the clinical presentation is that of hemodynamic collapse, or there is significant left ventricular systolic dysfunction. The role of amiodarone versus ICD, especially for patients with well-tolerated VT and milder forms of cardiomyopathies, is yet to be defined.

Cardiomyopathies↗

Effect of urea treatment on recovery of staphylococcal enterotoxin A from heat-processed foods.

The effects of urea treatment on the potential reactivation of heat-damaged antigenic components of staphylococcal enterotoxin A (SEA) were examined with cooked foods, including mushrooms, ham, bologna, salami, and turkey. The thermal stability of purified SEA spiked into foods and native SEA produced by Staphylococcus aureus in foods was also examined. Food samples containing either spiked or native SEA were thermally processed by autoclaving or retorting. This was followed sequentially by toxin extraction, urea treatment, dialysis, reconstitution, and SE assays with the reversed passive latex agglutination and/or enzyme immunoassay kit. The results indicate that (i) urea treatment did not result in any reactivation of heat-inactivated antigenic components of SEA in any of the foods tested, (ii) the serological components of purified SEA were destroyed (> or = 96%) by autoclaving at 121.1 degrees C for 5 to 15 min or by retorting at an F0 of 4 to 18, and (iii) the immunological property of the native SEA was approximately threefold-more heat resistant than that of the purified SEA. The study suggested that the current urea method is not suitable for the detection of heat-denatured SEA in the thermally processed foods.

Enterotoxins↗

Isolated porta hepatis metastasis of papillary thyroid cancer.

Metastases from differentiated thyroid cancer are usually seen in the cervical or mediastinal lymph nodes, lung or bone. We report a case of papillary thyroid cancer metastasizing to lymph nodes in the porta hepatis. No other site of metastasis was apparent on neck or abdominal exploration or on iodine whole-body scans. The primary tumor was a multifocal papillary thyroid cancer arising on a background of multinodular goiter. The metastasis was observed on a diagnostic radioiodine scan after surgical resection of the primary tumor despite significant (11%) radioiodine uptake by residual thyroid tissue in the neck and was proven by histologic examination and thyroglobulin immunohistochemistry. Although rare, metastasis to porta hepatis lymph nodes should be considered in the differential diagnosis of abdominal radioiodine uptake in patients with differentiated thyroid cancer.

Adult↗

Neutrophil-rich Ki-1-positive anaplastic large cell lymphoma presenting as a testicular mass.

Ki-1-positive large cell lymphoma is an uncommon subtype of lymphoma that may involve lymph nodes as well as a variety of extranodal locations. To the best of our knowledge, the occurrence of such a tumor in the testis has not been previously documented. We report a case of Ki-1-positive large cell anaplastic lymphoma presenting as a testicular mass in a 56-year old Saudi. Immunohistochemical staining revealed positive staining for Ki-1 and UCHL-1, which indicated a T-cell phenotype. This was further confirmed by polymerase chain reaction analysis, which demonstrated a monoclonal cell population with rearrangement of gamma T-cell receptor. Another interesting morphologic feature was the presence of large numbers of neutrophils throughout the tumor. Similar neutrophil-rich lymphomas have been described recently as a special subtype of Ki-1-positive anaplastic large cell lymphoma.

Anaplasia↗

Mechanistic kinship between hydroxylation and desaturation reactions: acyl-carbon bond cleavage promoted by pig and human CYP17 (P-450(17)alpha; 17 alpha-hydroxylase-17,20-lyase).

Using homogeneous pig and recombinant human CYP17, the mechanism of the acyl-carbon bond fission involved in the direct cleavage of pregnenolone was studied. It was found that the formation of androsta-5,16-dien-3 beta-ol (5,16-diene) and androst-5-ene-3 beta,17 alpha-diol (17 alpha-hydroxyandrogen) from pregnenolone was catalyzed by both the isoforms and that the two conversions were dependent on the presence of cytochrome b5 (cyt b5). 3 beta-Hydroxyandrost-5-ene-17 beta-carbaldehyde (aldehyde), an analogue of the physiological substrate pregnenolone, was handled as a substrate by both isoforms of CYP17. The aldehyde underwent cleavage to produce the 5,16-diene plus the 17 alpha-hydroxyandrogen, at rates approximately 8- and 3-fold higher than any physiological reaction catalyzed, in the absence of cytochrome b5, by the pig and human CYP17 isoforms, respectively. The stereochemistry of the reaction was studied using the aldehyde labeled with 2H at three strategic positions, 16 alpha, 16 beta, and 17 alpha, with incubations performed under both 16O2 and 18O2. The results showed that the formation of the 5,16-diene is attended by the removal of the 16 alpha-hydrogen atom; all three 2H atoms are retained in the formation of 17 alpha-hydroxyandrogen and its 17 alpha-hydroxyl oxygen originates from O2. Irrespective of the nature of the substrate, or the enzymic conditions used, the 5,16-diene and 17 alpha-hydroxyandrogen were produced in similar ratios, suggesting that their genesis is closely linked. Both the compounds may be envisaged to arise from a peroxy adduct that fragments to give a carbon radical that then undergoes either a disproportionation or an oxygen-rebound reaction. The conclusion was supported by isotope-partitioning experiments when the conversion of a mixture of the unlabeled aldehyde and its isotopomer, containing 2H at 16 alpha as well as 16 beta, led to the enrichment of 2H in 17 alpha-hydroxyandrogen. It is suggested that the mechanistic kinship between hydroxylation and olefin formation, revealed by the present study, also applies to conventional hydroxylation and desaturation reactions.

Aldehyde-Lyases↗

Provocation of hypotension during head-up tilt testing in subjects with no history of syncope or presyncope.

BACKGROUND: Head-up tilt test is increasingly being used to evaluate patients with syncope. This study was designed to evaluate the specificity of head-up tilt testing using different tilt angles and isoproterenol infusion doses in normal volunteers with no prior history of syncope or presyncope. METHODS AND RESULTS: One hundred fifty volunteers were randomized to two groups of 75 each. In group 1, subjects were further randomized to have head-up tilt testing at a 60, 70, or 80 degree angle at baseline followed by repeat tilt testing during a low-dose isoproterenol infusion that increased the heart rate by an average of 20%. In group 2, after having a baseline head-up tilt test at a 70 degree angle for a maximum of 20 minutes, subjects were randomized to have a repeat tilt table testing at a 70 degree angle during a low-dose, 3 micrograms/min, or 5 micrograms/min isoproterenol infusion. In group 1, syncope or presyncope along with hypotension developed in 2 subjects during the baseline test at 60 and 70 degrees of tilt and in 5 subjects during tilting at 80 degrees. The addition of low-dose isoproterenol reduced the specificity minimally from 92% to 88% at both 60 and 70 degrees of tilt but substantially to 60% at an 80 degrees angle. However, 6 of the 10 subjects with a positive test at an 80 degree angle had an abnormal response after 10 minutes of tilt testing. In group 2, using various isoproterenol doses with tilt table testing at a 70 degree angle, low-dose (mean infusion dose, 1.5 +/- 0.45 microgram/min), 3 micrograms/min, and 5 micrograms/min isoproterenol infusions elicited an abnormal response in 1 (4%), 5 (20%), and 14 (56%) of the subjects, respectively. Using multiple logistic regression analysis, head-up tilt testing at an 80 degree angle (P = .01) or during 3 micrograms/min (P = .02) and 5 micrograms/min isoproterenol infusion rates (P < .001) was the most significant predictor of an abnormal response. CONCLUSIONS: Head-up tilt testing at a 60 or 70 degree angle with or without low-dose isoproterenol infusion provides an adequate specificity. Caution is needed, however, in interpreting the results if the head-up tilt test at 80 degrees is extended beyond 10 minutes or if high doses of isoproterenol are used.

Adult↗

Modulation of the activity of human 17 alpha-hydroxylase-17,20-lyase (CYP17) by cytochrome b5: endocrinological and mechanistic implications.

Using NADPH-cytochrome P-450 reductase as electron donor the homogeneous pig 17 alpha-hydroxylase-17,20-lyase (CYP17) was shown to catalyse the conversion of delta 5, as well as delta 4, steroids (pregnenolone and progesterone respectively) predominantly into the corresponding 17 alpha-hydroxylated products. The latter were then cleaved by the lyase (desmolase) activity of the enzyme into androgens. Cytochrome b5 stimulated both these activities, but its most noticeable effect was on the formation of delta 16-steroids, which compulsorily required the presence of cytochrome b5. These results on the pig enzyme confirm the original findings [Nakajin, Takahashi, Shinoda and Hall (1985) Biochem. Biophys. Res. Commun. 132, 708-713]. The human CYP17 expressed in Escherichia coli [Imai, Globerman, Gertner, Kagawa and Waterman (1993) J. Biol. Chem. 268, 19681-19689] was also purified to homogeneity and was found to catalyse the hydroxylation of pregnenolone and progesterone without requiring cytochrome b5. Like the pig CYP17, the human CYP17 also catalysed the cytochrome b5-dependent direct cleavage of pregnenolone into the delta 5,16-steroid, but unlike it the human enzyme did not cleave progesterone at all. 17 alpha-Hydroxypregnenolone was, however, cleaved into the corresponding androgen but only in the presence of cytochrome b5. 17 alpha-Hydroxyprogesterone was a poor substrate for the human CYP17; although it was converted into androstenedione in the presence of cytochrome b5 its K(m) was 5 times higher and Vmax. 2.6 times lower than those for the hydroxylation of progesterone. The endocrinological and mechanistic implications of these results are discussed.

Adrenal Cortex Hormones↗

Characterization of atrioventricular nodal behavior and ventricular response during atrial fibrillation before and after a selective slow-pathway ablation.

BACKGROUND: The presence of atrioventricular nodal dual-pathway physiology in patients with atrioventricular nodal reentrant tachycardia (AVNRT) provides an opportunity to characterize the effect of a selective slow-pathway ablation on the ventricular rate during atrial fibrillation (AF). This may have important clinical implications for the nonpharmacological management of AF with a rapid ventricular rate. METHODS AND RESULTS: Selective radiofrequency catheter ablation of the atrioventricular nodal slow pathway was performed with a stepwise approach in patients with documented sustained AVNRT. The AV nodal conduction properties and refractoriness and the ventricular rate during induced AF were assessed at baseline and under autonomic blockade before and after a selective slow-pathway ablation in 18 patients (mean age, 34 +/- 8 years). Sustained AVNRT was induced with a mean cycle length of 339 +/- 58 ms. A slow-pathway ablation was successfully achieved with 5 +/- 4 applications of radiofrequency energy. The shortest cycle length of 1:1 AV conduction and the AV nodal effective refractory period significantly prolonged after ablation (367 +/- 53 versus 403 +/- 55 ms, P < .0001, and 258 +/- 55 versus 292 +/- 74 ms, P < .05, respectively). Selective slow-pathway ablation significantly prolonged the mean (526 +/- 93 versus 612 +/- 107 ms, P < .0001), the shortest (378 +/- 59 versus 423 +/- 73 ms, P < .0001), and the longest (826 +/- 150 versus 969 +/- 226 ms, P < .01) cycle lengths of the ventricular response to AF. Significant slowing of the ventricular rate during AF occurred in 13 patients (72%), including all eight patients in whom AV nodal dual-pathway physiology was abolished. Five patients did not have a significant change in the ventricular rate during AF; a persistent dual AV nodal pathway physiology was demonstrable in four of these patients. Loss of dual-pathway physiology after ablation had a sensitivity of 77%, specificity of 80%, and positive predictive value of 91% for slowing the ventricular rate during AF. CONCLUSIONS: In patients undergoing a slow-pathway ablation for control of AVNRT, selective slow-pathway ablation may cause a significant decrease in the ventricular rate during AF. These effects are primarily due to the prolongation of AV nodal conduction properties and refractory period of the residual AV nodal transmission system. These findings may have important therapeutic implications for the nonpharmacological treatment of AF, particularly in patients with underlying dual AV nodal physiology.

Adult↗

Termination of atrioventricular nodal reentrant tachycardia by premature stimulation from ablating catheter. A reliable guide to identify site for slow-pathway ablation.

BACKGROUND: Slow-pathway ablation is currently used more frequently to control atrioventricular nodal reentrant tachycardia (AVNRT). However, in patients with the common type of AVNRT, successful ablation of the slow pathway can be difficult and time-consuming. We tested a simple method to predict a site for slow-pathway ablation in patients with AVNRT of the common variety. METHODS AND RESULTS: Twenty patients with symptomatic common AVNRT (13 women and 7 men; mean age, 41 +/- 21 years) were included in the study. Once the AVNRT had a stable cycle length (+/- 10 ms) for at least 20 cycles, single extrastimuli were delivered from the ablating catheter tip beginning with 20 ms less than the tachycardia cycle length and decrementing by 10 ms until tachycardia terminated or loss of capture occurred at the pacing site. The pacing protcol was performed systematically in a stepwise fashion at four adjacent sites starting from the posterior/inferior interatrial septum near the tricuspid annulus and moving progressively more anteriorly. The pacing protocol was then repeated in the same sequence, followed by delivery of radiofrequency current at each site to determine its effect at sites where AVNRT could not be terminated with a pacing protocol. AVNRT could be terminated in the anterograde direction from at least one site in 19 patients. Tachycardia could be terminated at two or more adjacent sites in 5 patients. The longest atrial coupling interval at the site of tachycardia termination was 67 +/- 27 ms (range, 30 to 130 ms) less than the AVNRT cycle length. Resetting of subsequent His bundle depolarization (H2), producing an H-H2 interval prolongation of 26 +/- 24 ms (range, 10 to 80 ms), occurred in 17 patients before termination of the tachycardia. In 18 of the 19 patients, the slow pathway was successfully ablated at the site at which AVNRT was terminated at the longest atrial coupling interval. CONCLUSIONS: Termination of tachycardia in the anterograde direction at the longest atrial coupling interval by extrastimuli delivered from the ablating catheter can be helpful for identification of an optimal site for slow-pathway ablation in patients with the common variety of AVNRT.

Adult↗

Relevance of asystole during head-up tilt testing.

The prognosis of patients manifesting prolonged asystole during head-up tilt testing is unclear. In 209 consecutive patients with a history of syncope and positive head-up tilt tests, 19 had asystole lasting > 5 seconds (mean duration 15 +/- 10) (group 1a). When compared with patients without asystole (group 1b), group 1a patients were younger (32 +/- 12 vs 47 +/- 21 years, p < 0.005), but clinical manifestations were not any more dramatic (the number of episodes of syncope [7 +/- 5 vs 8 +/- 6 episodes, p = NS] and injury during syncope [2 vs 13 patients, p = NS] were similar). During follow-up (mean 2 +/- 1 year), with the patient taking pharmacologic therapy such as beta blockers, ephedrine, theophylline, or disopyramide, the recurrence rate was 11% and 8% in groups 1a and 1b (p = NS). No patient in the asystole group underwent pacemaker implantation. Additionally, of 75 normal volunteers (group 2) with no history of syncope undergoing tilt tests to define its specificity, 3 had asystole (mean duration 10 seconds). During > 1 year of follow-up, despite no treatment, all 3 are symptom free. Thus, asystole during head-up tilt testing does not predict either a more malignant outcome or a poor response to pharmacologic therapy. Moreover, an asystolic response does not enhance the specificity of the head-up tilt test because it may be present in asymptomatic "normal" volunteers.

Adolescent↗

Aspiration cytology of chromophobe cell carcinoma of the kidney.

Fine-needle aspiration biopsy findings in three cases of chromophobe cell carcinoma are described and correlated with histologic and ultrastructural observations. In addition, comparisons are made with three cases each of oncocytoma and granular cell carcinoma. The cells in aspiration smears from chromophobe cell carcinoma closely correlated with histologic pattern of three cell types which were not present in oncocytomas and granular cell carcinomas. These cells had prominent cell borders, and their cytoplasm was either opaque and granular (type I) or variably translucent and reticular (type II and III). Ultrastructurally, the translucent areas within the cytoplasm contained large numbers of microvesicles which were unique to chromophobe cell carcinoma and were not seen in other neoplasms. Fine-needle aspiration may be used to diagnose chromophobe cell carcinoma and distinguish it from other related renal neoplasms.

Adenocarcinoma↗