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Biomedical subjects

M Akhtar

Publications and source records attributed to M Akhtar.

At least 109 records · Page 6Linked to original sources
PubMed1997

Efficacy of midodrine hydrochloride in neurocardiogenic syncope refractory to standard therapy.

INTRODUCTION: Some patients with neurocardiogenic syncope continue to have recurrent syncope or presyncope despite the use of currently available drug therapy. The purpose of this study was to determine whether midodrine hydrochloride, a selective adrenergic agonist, could be effective in patients resistant to, or intolerant of, currently used medications in the treatment of neurocardiogenic syncope. METHODS AND RESULTS: Eleven patients with a history of recurrent syncope or presyncope in whom hypotension with syncope or presyncope could be provoked during head-up tilt testing were included. There were 4 men and 7 women with a mean age (+/-SD) age of 34 +/- 13 years. In all patients, standard therapy with beta-adrenergic receptor blocking agents, ephedrine, theophylline, disopyramide, fludrocortisone, and sertraline hydrochloride, was either ineffective, poorly tolerated, or contraindicated. Midodrine was initially administered orally at a dose of 2.5 mg three times daily. After adjustment of dosage over 2 to 4 weeks, patients were followed-up clinically. Midodrine was discontinued in one patient because of side effects. Frequency of syncope or presyncope during the 3 months prior to starting treatment was compared during a mean follow-up of 17 +/- 4 weeks after starting treatment with midodrine. There was significant (P < 0.01) reduction in syncopal and presyncopal episodes on midodrine. Five patients had complete resolution of symptoms, while four patients had significant improvement. Symptoms did not improve in one patient. CONCLUSIONS: Midodrine hydrochloride can be effective in preventing recurrent symptoms in selected patients with neurocardiogenic syncope unresponsive to, or intolerant of, standard drug therapy.

Administration, Oral↗
PubMed1997

Delivery of noncommitted shocks for nonsustained ventricular arrhythmias by a new implantable cardioverter defibrillator with abortive shock capability.

INTRODUCTION: To describe the delivery of noncommitted implantable cardioverter defibrillator (ICD) shocks despite self-termination of ventricular arrhythmias. Abortive shock capability should eliminate the delivery of shocks for self-terminating ventricular arrhythmias. The delivery of noncommitted shocks despite abortive shock capability is, therefore, unexpected and previously unreported. METHODS AND RESULTS: Among 118 patients who received the Transvene nonthoracotomy lead system and the Jewel ICD (model 7219D), three patients (1.7%) experienced supurious, noncommitted shocks for self-terminating arrhythmias. Only one detection zone (i.e., ventricular fibrillation) had been programmed in the defibrillator in each patient. In all three patients, the ventricular arrhythmias self-terminated during the charging period. One patient received seven shocks during periods of asystole, and the other two patients received one shock each. Two different mechanisms for shock delivery in this setting were identified: one occurring in the absence of electrical activity at the end of the bradycardia escape interval (i.e., associated with bradyarrhythmias), and the other when two sensed electrical events (i.e., escape beats) occurred during the so-called "synchronization" window of the defibrillator. CONCLUSIONS: In rare patients with the Jewel defibrillator, shocks may be delivered for self-terminating arrhythmias despite abortive shock capability. Patients who are dependent upon pacing from their implanted defibrillator are at particular risk for shock in the aftermath of self-terminating ventricular arrhythmias. Defibrillator programming strategies aimed at eliminating or diminishing the incidence of this problem are discussed.

Aged↗
PubMed1997

Specific genetic changes of diagnostic importance in chromophobe renal cell carcinomas.

The histologic diagnosis of chromophobe renal cell carcinomas is often uncertain because of phenotype overlap among different types of kidney cancers. Recently, in a novel genetic classification of renal cell tumors, a combination of monosomies of chromosomes 1, 2, 3, 6, 10, 13, 17, and 21 have been suggested to have a diagnostic value for this unique type of tumor. Therefore, we have analyzed fresh and paraffin-embedded tissues obtained from 42 chromophobe renal cell carcinomas for allelic losses at the above-mentioned chromosomal regions by employing microsatellite markers. Loss of chromosomes 1, 2, 6, 10, 13, and 17 was detected in between 75% and 95% of tumors, and loss of chromosome 21 was observed in 54% of cases. All but one tumor showed a combination of monosomies at the specific chromosomes. Thus, applying the set of microsatellite markers used in this study, a PCR-based diagnosis of chromophobe renal cell carcinomas could be established within 1 to 2 days. The general applicability of this approach to fresh and paraffin-embedded tissues allows a correct genetic characterization in all cases where a diagnosis based on histopathology remains uncertain.

Alleles↗
PubMed1997

The impact of aromatase mechanism on other P450s.

Experimental findings from a number of laboratories have converged to show that the conversion of androgens into oestrogen, catalysed by aromatase, involves three distinct reactions which occur at a single active site. That each one of these reactions belongs to a different generic type was revealed by chemical consideration, together with our (18)O-experiments. In particular, these findings highlighted the fact that the third reaction in the sequence occurs by a novel process for which a number of plausible mechanisms have been considered. The scrutiny of these mechanisms has involved either studies on aromatase itself, or on related enzymes which catalyse the aromatase type of cleavage reaction as generalized in equation 1: [equation: see text]. The acyl-carbon cleavage reaction of equation 1 is catalysed by sterol 14alpha-demethylases, accounts for several side-chain fission products formed by CYP17 (17alpha-hydroxylase-17,20-lyase), and constitutes a weak property of certain drug metabolizing P450s, when given aliphatic aldehydes as substrates. From cumulative studies on these enzymes, consensus is beginning to emerge that the acyl-carbon fission may be promoted by the FeIII-OOH intermediate, formed during the catalytic cycles of P450s. The precedent for the direct involvement of the FeIII-OOH species in the reaction of equation 1 is influencing our thinking regarding the mechanism of the conventional hydroxylation reaction. The status of knowledge surrounding the current debate on these issues will be reviewed.

Aromatase↗
PubMed1996

Feasibility of atrial fibrillation detection and use of a preceding synchronization interval as a criterion for shock delivery in humans with atrial fibrillation.

OBJECTIVES: This study assessed the feasibility of detecting atrial fibrillation (AF) and delivery of appropriately timed R wave shocks using an implantable atrial defibrillator. BACKGROUND: For atrial defibrillation therapy to be feasible in an implantable form, AF must be detected in a specific fashion, and the risk of ventricular proarrhythmia should be minimized. METHODS: Eleven patients with AF underwent testing with an implantable atrial defibrillator (METRIX 3000 Automatic Atrial Defibrillator, InControl, Inc.). Wideband electrograms (EGMs) were recorded from the right ventricular (RV) bipolar catheter and from the multipolar catheters located in the right atrium (RA) and coronary sinus (CS). Atrial fibrillation detection was performed using two serial algorithms-quiet interval analysis and baseline crossing analysis-that detect atrial activity on the RA-CS channel. Ventricular sensing using a minimal preceding synchronization interval of 500 ms as a criterion for synchronous shock delivery was performed from filtered RV and RV-CS EGMs. RESULTS: The AF detection algorithms were applied to 53 AF data segments and 18 normal sinus rhythm data segments. Atrial fibrillation was detected appropriately in 49 instances, and the specificity for detecting AF and normal sinus rhythm was 100%. Synchronization criterion efficacy was assessed by delivering shock markers and shocks. Of the 2,025 R waves processed, 557 (27.5%) were marked as suitable for shock delivery. In addition, 69 therapeutic and 11 test shocks were delivered during AF. All shock markers and shocks were delivered synchronously with the R wave, and the synchronization criterion was never violated. CONCLUSIONS: Atrial fibrillation can be detected in a specific fashion using the RA-CS lead configuration and serial detection algorithms for atrial sensing. The delivery of properly timed shocks is feasible and should minimize the risk of ventricular proarrhythmia.

Adult↗
PubMed1996

Studies of the p53 gene mutation in Saudi non-Hodgkin's lymphoma.

Tumor biopsies (paraffin embedded tissue) obtained from 45 Saudi patients with non-Hodgkin's lymphoma (NHL) were examined for the incidence of p53 mutations screened by polymerase chain reaction (PCR) and single strand conformation polymorphism (SSCP) analysis. DNA sequencing was carried out to confirm the occurrence of p53 mutation in PCR products showing abnormal migration by SSCP analysis. Only 1/45 samples showed the incidence of a homozygous mutation at codon 179 (exon 5) of the p53 gene that replaces histidine with tyrosine. The data showed that the frequency of p53 mutations was very low in Saudi NHL. Our results are consistent with the general observation that the p53 mutation is rather infrequent in hematopoietic malignancies like NHLs.

Adolescent↗
PubMed1996

The mechanism of the acyl-carbon bond cleavage reaction catalyzed by recombinant sterol 14 alpha-demethylase of Candida albicans (other names are: lanosterol 14 alpha-demethylase, P-45014DM, and CYP51).

The Candida albicans sterol 14 alpha-demethylase gene (P-45014DM, CYP51) was transferred to the yeast plasmid YEp51 placing it under the control of the GAL10 promoter. The resulting construct (YEp51:CYP51) when transformed into the yeast strain GRF18 gave a clone producing 1.5 mu mol of P-450/liter of culture, the microsomal fraction of which contained up to 2.5 nmol of P-450/mg of protein. Two oxygenated precursors for the 14 alpha-demethylase, 3 beta-hydroxylanost-7-en-32-al and 3 beta-hydroxylanost-7-en-32-ol, variously labeled with 2H and 18O at C-32 were synthesized. In this study the conversion of [32-2H,32-16O]- and [32-2H,32-18O]3 beta-hydroxylanost-7-en-32-al with the recombinant 14 alpha-demethylase was performed under 16O2 or 18O2 and the released formic acid analyzed by mass spectrometry. The results showed that in the acyl-carbon bond cleavage step (i.e. the deformylation process) the original carbonyl oxygen at C-32 of the precursor is retained in formic acid and the second oxygen of formate is derived from molecular oxygen; precisely the same scenario that has previously been observed for the acyl-carbon cleavage steps catalyzed by aromatase (P-450arom) and 17 alpha-hydroxylase-17,20-lyase (P-45017 alpha,CYP17). In the light of these results the mechanism of the acyl-carbon bond cleavage step catalyzed by the 14 alpha-demethylase is considered.

Base Sequence↗
PubMed1996

Novel mechanism for the activation of rhodopsin kinase: implications for other G protein-coupled receptor kinases (GRK's).

ATP, its nonhydrolyzable analogue, AMP-PNP, and albumin were found to promote the dissociation of rhodopsin kinase from rod outer segments (ROS) containing photoactivated-rhodopsin (Rho*). These features were embodied in a protocol for the recovery of rhodopsin kinase from incubations containing ROS which had been subjected to a wide range of treatments. It was found that the supernatants recovered from mixtures containing ATP, rhodopsin kinase, and photolyzed ROS membranes catalyzed a Rho*-independent peptide phosphorylation as well as dark-phosphorylation of rhodopsin. The activities of this activated kinase in the two aforementioned assays were 7-8% of the maximum intrinsic activity found in appropriate standard assays (i.e., light-stimulated phosphorylation of rhodopsin and Rho*-dependent peptide phosphorylation). The activated kinase reverted to its inactive resting-state in a time dependent fashion, giving a tau 1/2 of decay of approximately 2 min. The intrinsic activity of kinase as measured by the standard assay, however, remained constant during this decay period. No positive evidence was found to suggest that the interconversion activated kinase <--> inactive kinase occurred by a phosphorylation event. Cumulatively, the results show that the interaction of rhodopsin kinase.ATP complex with Rho* leads to the formation, presumably due to the reorganization of the protein structure, of a soluble active kinase species which reverts to the inactive resting state in a time-dependent fashion.

Adenosine Triphosphate↗
PubMed1996

Recurrence of neurocardiogenic syncope without pharmacologic interventions.

In 54 patients with positive tilt and who refused medical therapy, we observed a significant decrease in the frequency of syncopal spells after diagnosis and counseling. However, symptoms were reported at follow-up by 64.8% of the patients and were predicted by the frequency and total number of syncope episodes before upright tilt.

Adult↗
PubMed1996

Unmasking the trifascicular left intraventricular conduction system by ablation of the right bundle branch.

Twenty-five patients underwent transcatheter right bundle ablation either for bundle branch reentrant tachycardias or inadvertent or deliberate right bundle ablation during atrioventricular junctional ablation for rate control. Electrophysiologic data and 12-lead electrocardiograms before and after right bundle ablation were available in all patients. Eleven of the patients had no significant intraventricular conduction abnormalities by surface electrocardiograms (group I), whereas 14 patients had underlying intraventricular conduction delays (group II). All group I patients had typical electrocardiographic changes of right bundle branch block after right bundle ablation, with minimal changes in initial or mean QRS axis. In group II, 5 patients had an initial 40 ms QRS axis shift of > 45 degrees, in 7 patients the mean QRS axis changed significantly (leftward in 4 and rightward in 3), and a qR pattern in V1 was seen in 12 of 14 patients including 2 with structurally normal hearts. These changes, namely new Q waves, and rightward and leftward axis shifts are most likely the result of septal fascicular, left posterior fascicular, and left anterior fascicular delay/block, which were exposed by exclusive conduction via a diseased left bundle and its fascicles. The trifascicular nature of left intraventricular conduction is more apparent when diseased and unmasked by concomitant block in the right bundle branch.

Aged↗
PubMed1996

Undetected ventricular fibrillation in transvenous implantable cardioverter-defibrillators. Prospective comparison of different lead system-device combinations.

BACKGROUND: The purpose of this study was to prospectively analyze redetection problems after unsuccessful shock with different lead systems and devices. METHODS AND RESULTS: We prospectively analyzed detection and redetection characteristics among transvenous implantable cardioverter-defibrillators (ICDs) using standard bipolar and integrated bipolar sensing. Monophasic and biphasic ICDs were included. Subthreshold shocks were intentionally delivered, and redetection of ventricular fibrillation (VF) was assessed before discharge and at 1, 3, 6, and 12 months later. Sensing of VF resulting from antitachycardia pacing and low-energy cardioversion ( < or = 2 J) also was analyzed. Before inclusion in the study, each patient underwent subthreshold shock testing at three different time intervals. Among the 160 ICDs with standard bipolar sensing, 530 VF inductions were analyzed. After the failed shocks, undersensing was more frequent (3% versus 20%, P<.01) but did not remarkably prolong redetection (3.1 +/- 0.8 versus 3.3 +/- 1.1 seconds). Among the 201 ICDs with integrated bipolar sensing, 80 were connected to a CPI device (60 Ventak 1600-Endotak 60 series and 20 PRx II 1715-Endotak 70 series) and 121 to the Ventritex defibrillator (91 Endotak 60 series, 14 TVL systems, and 16 Endotak 70 series). After 252 failed shocks, redetection was prolonged with the CPI system (3.1 +/- 1.4 versus 4.6 +/- 3.6 seconds, P<.05) but did not change after 396 failed shocks with the Ventritex ICD (5.4 +/- 1.9 versus 4.9 +/- 2.2 seconds). This may reflect different nominal settings for detection and redetection. In 9 of 121 patients with Ventritex and 1 of 80 with the CPI ICDs, the devices failed to redetect VF. However, redetection malfunction was never observed in patients with integrated bipolar systems with >6-mm electrode separation. After antitachycardia pacing in 1 patient and a 2-J shock in 1 patient, ventricular tachycardia turned into VF, which was undetected. Both patients used the Endotak 60 series-Cadence combination. None of the patients showing VF undersensing had sudden death at follow-up. Only 3 of the 12 patients with sensing malfunction were on antiarrhythmia drugs at the time of testing. Analysis of endocardial electrograms showed that failure to redetect VF is not associated with a uniform reduction but with a rapid and repetitive change of electrogram amplitude. CONCLUSIONS: Standard bipolar sensing redetects VF more effectively than integrated bipolar sensing. Endocardial electrogram analysis provides insights into the understanding of the mechanism of undersensing, and certain lead-device combinations result in a higher occurrence of VF undersensing. The clinical relevance of this phenomenon remains unknown.

Adult↗
PubMed1996

Distribution of atrial electrogram types during atrial fibrillation: effect of rapid atrial pacing and intercaval junction ablation.

OBJECTIVES: This study examined the anatomic distribution types and possible determinant of atrial electrogram types during atrial fibrillation. BACKGROUND: Different types of atrial electrograms during atrial fibrillation have been observed and classified, but their anatomic distribution patterns, determinants and potential usefulness in guiding future catheter ablation are unknown. METHODS: Two animal models of atrial fibrillation were used: the sterile pericarditis model (n = 10) and the rapid atrial pacing model (400 beats/min for 6 weeks, n = 6). The atrial electrogram of atrial fibrillation and the atrial effective refractory period were obtained from multiple sites of the right and left atrium. In addition, decremental rapid atrial stimulation was applied to the site of shortest and longest atrial effective refractory periods until atrial fibrillation induction in a subgroup of nine dogs. Ablation of the intercaval junction was performed using the radiofrequency catheter technique in dogs with atrial fibrillation duration > 1 min. RESULTS: In both models, organized atrial electrograms (type I) were predominantly observed at the left atrial sites and the right atrial appendage, whereas disorganized atrial electrograms (type III) were mainly observed at the right posterolateral atrium. The distribution of the atrial electrogram types closely followed that of the atrial effective refractory period, with the shortest atrial effective refractory period corresponding to organized atrial electrograms (type I) and the longest atrial effective refractory period corresponding to disorganized atrial electrograms (type III). The correlation of atrial electrogram type with the atrial effective refractory period was further demonstrated by the effect of rapid atrial stimulation. When rapid atrial stimulation was applied to the site with the shortest atrial effective refractory period, disorganized atrial electrograms were observed at sites with the longest atrial effective refractory period, whereas 1:1 atrial capture was still present at the stimulation site. Ablation of the intercaval junction made atrial fibrillation noninducible or tended to shorten the atrial fibrillation duration (from 26.4 +/- 24.2 to 8.8 +/- 22.6 min in the pericarditis group, p = 0.02, and from 33.7 +/- 29.2 to 12.1 +/- 23.8 min in the rapid pacing group, p = 0.09) but did not change the atrial electrogram types during atrial fibrillation. CONCLUSIONS: Various types of atrial electrograms are present at different locations during atrial fibrillation. The atrial electrogram characteristics of atrial fibrillation at a specific location are related to the atrial effective refractory period, with short effective refractory periods associated with organized atrial electrograms and long effective refractory periods associated with disorganized electrograms.

Animals↗
PubMed1996

Sudden death in patients with implantable cardioverter-defibrillators.

UNLABELLED: Of the 733 patients with implantable cardioverter-defibrillators (ICDs) from 1982 to 1995 in our center, 20 died suddenly while the ICD was activated. This number included 16 men and four women with a mean age of 60 +/- 8 years and ejection fractions of 24.2% +/- 8.6%. ICDs were implanted for drug refractory ventricular tachycardia (VT) in 13 patients and for resucitated cardiac arrest in seven patients. The clinical VT was associated with syncope in 7 of 13 patients. VT was induced in 18 patients and was hemodynamically unstable in 12 patients. Shock therapies associated with syncope were delivered in 7 of 15 patients during the follow-up. This subgroup of patients survived a median of only 18 months after ICD implant. Ventricular fibrillation-defibrillation was found to surround death in nine patients. CONCLUSIONS: (1) Sudden death victims of the ICD population are characterized by poor left ventricular function and hemodynamically unstable ventricular tachyarrhythmias. (2) Ventricular tachyarrhythmias are the major cause of sudden death in ICD patients.

Aged↗
PubMed1996

Cytogenetic findings in renal cell carcinoma.

Cytogenetic characterization of 24 renal cell carcinomas (RCCs) was performed. The various RCC subtypes included 8 chromophobe RCCs, 12 nonpapillary RCCs, and 4 papillary RCCs. Loss of chromosomes 1, 2, 6, 10, and 17 were observed in 5 of 8 chromophobe RCCs. Five of the 12 nonpapillary RCCs showed abnormalities involving chromosome 3. These were deletion of the 3p13 region, loss of the whole chromosome 3, and unbalanced translocation resulting in a derivative. Of the 4 papillary RCCs, two showed trisomy 7 and 17 along with other abnormalities, one had trisomy for chromosomes 7, 12, and 13, along with loss of chromosome #5 and Y chromosomes, and another papillary RCC revealed trisomy 15 and trisomy 17. These results further show that specific cytogenetic abnormalities are associated with various subtypes of RCCs.

Adult↗
PubMed1996

Pattern of glomerular disease in Saudi Arabia.

Clinical data and renal biopsy study of 186 adult patients found to have nephropathy and seen at the Security Forces Hospital, Riyadh, over a 5-year period (1989 to 1994) were reviewed. Primary glomerular disease accounted for more than three fourths of all patients (79%), and the most common histological lesion was focal segmental glomerulosclerosis (40.8%) associated with a high incidence of hypertension (86.7%), nephrotic syndrome (61.7%), hematuria (48.8%), and renal impairment (33.3%). Mesangioproliferative glomerulonephritis was the second most common lesion (21.1%), followed by membreous glomerulonephritis (13.6%), immunoglobulin A nephropathy (IgAN) (13.6%), membranoproliferative glomerulonephritis (9.5%), and minimal change disease (1.4%). Although not as common as in most other developed countries, IgAN is being increasingly recognized in Saudis. Lupus nephritis remained the commonest cause of secondary glomerulonephritis (48.5%), whereas amyloidosis was conspicuously absent. There is no evidence, at least in this series, that chronic infection such as hepatitis B virus infection has a major role in the development of glomerulonephritis.

Adult↗