Search PubMed⌕ Search

Biomedical subjects

M Akhtar

Publications and source records attributed to M Akhtar.

At least 145 records · Page 8Linked to original sources
PubMed1995

Sneddon's syndrome: a systemic arterio-occlusive disorder.

We describe a case of Sneddon's syndrome in a young woman with malignant hypertension and renal impairment. Kidney biopsy demonstrated intimal proliferation of small and medium-sized renal arteries similar to that seen in cutaneous arteries of patients with this syndrome. Ultrastructural examination showed the proliferated intima to be composed of smooth muscle fibers, fibroblasts, monocytes, and extensive deposition of dense granular and light-staining amorphous materials. Our findings support the proposition that Sneddon's syndrome may not be simply a neurocutaneous vascular disorder as originally described, but rather a systemic arterioocclusive disorder with a variable clinical expression.

Adult↗
PubMed1995

Henderson-Hasselbalch equation is inadequate for the measurement of transmembrane diffusion of drugs and buccal drug absorption is a useful alternative.

1. The transmembrane diffusion of weakly acidic or basic drugs is being commonly assessed from their degree of ionization or ratio unionized/ionized forms (ratio U/I) as calculated from Henderson-Hasselbalch equation (HHEq). 2. Buccal drug absorption (BA) at pH 5-9 has been proposed as an in vivo model for passage of drugs across lipid membranes. 3. Area under the curve (AUC) of BA against pH 5-9 of 18 basic drugs has been reported to be significantly related to their pH dependent renal excretion. 4. We have calculated, using HHEq, ratios U/I of 10 weak bases at pH 5-9 and 10 weak acids at pH 4-8, whose percentage BA at these pH levels was available in the literature. 5. These ratios were not related to their %BA at corresponding pH levels. 6. Therefore it is proposed that HHEq is inadequate in the anticipation of transmembrane diffusion of drugs and AUC of %BA of drugs at pH 4-9 is a useful alternative.

Absorption↗
PubMed1995

Chromophobe cell carcinoma of the kidney. A clinicopathologic study of 21 cases.

The clinicopathologic features in a series of 21 chromophobe cell carcinomas are reviewed. Patients' ages ranged from 30 to 83 years (mean, 53 years), and the number of men and women was roughly equal. Major presenting complaints included hematuria, flank pain, and flank mass. All but two tumors were staged as tumor node metastasis (TNM) T2N0M0. Histologically, the carcinomas were composed of large cells with variably reticulated, translucent cytoplasm. The tumor cells could be divided into three types according to the extent and distribution of reticulated cytoplasm. Ultrastructurally, these reticulated areas were characterized by the presence of large numbers of microvesicles, which appeared to be unique to chromophobe cell carcinomas because ultrastructural examination of 20 clear cell carcinomas and six granular cell carcinomas failed to reveal similar structures. The origin of the vesicles appeared to be from saccular outpouchings from the outer mitochondrial membrane. Immunohistochemical studies revealed that all the tumors were variably positive for cytokeratins 8, 18, and 19, and epithelial membrane antigen but negative for vimentin. Flow cytometric DNA analysis of eight carcinomas revealed slightly hypodiploid cell populations in seven tumors. Of these, four also contained hyperdiploid cell populations. Follow-up (6-108 months) of 16 patients revealed all these patients to be alive and well. These findings further confirm the concept that chromophobe cell carcinoma is a special subtype of renal cell carcinoma in which the presence of microvesicles is a characteristic morphologic feature. Furthermore, loss of chromosomal DNA may also be a frequent, perhaps unique, feature of chromophobe cell carcinoma.

Adenocarcinoma↗
PubMed1995

Comparison of biphasic and monophasic pulses: does the advantage of biphasic shocks depend on the waveshape?

With present implantable defibrillators, the ability to vary the defibrillation technique has been shown to increase the number of patients suitable for transvenous system. As newer waveforms become available, the need for a flexible device may change. In addition, although it has been shown that the option of biphasic waveform may increase the defibrillation efficacy, this may depend upon the shape of the biphasic waveform used. Thirty patients undergoing transvenous defibrillator implant were included in the study. In 20 patients (group I), defibrillation efficacy of simultaneous monophasic, sequential monophasic, and biphasic waveform with 50% tilt was determined randomly. Similarly, in ten patients (group II) testing of simultaneous monophasic shocks and biphasic waveforms with 65% and 80% tilt was performed in random order. The electrode system used consisted of two transvenous leads and a subcutaneous patch in all 30 patients. In group I, 50% tilt biphasic waveform consistently provided similar or better defibrillation efficacy compared to monophasic waveforms (biphasic 7.5 +/- 5.1 joules vs simultaneous 17 +/- 7.8 joules, P < 0.01; and vs sequential 17 +/- 8.4 joules, P < 0.01). In group II, 65% tilt biphasic pulse required less energy for defibrillation as compared with simultaneous monophasic shocks (9.6 +/- 4.5 joules vs 15.6 +/- 5.1 joules, P = 0.04). No significant difference was observed in terms of defibrillation threshold between 80% tilt biphasic shocks and simultaneous monophasic pulses (11.8 +/- 6 joules vs 15.6 +/- 5.1 joules, P = NS). Biphasic shocks with smaller tilt delivered using a triple lead system more uniformly improved defibrillation threshold over standard monophasic waveforms.

Defibrillators, Implantable↗
PubMed1995

Effects of initial polarity on defibrillation threshold with biphasic pulses.

BACKGROUND: Previous studies have shown that the polarity of epicardial patches significantly affects the defibrillation efficacy of monophasic shocks. However, whether this improvement can be extended to different pulsing methods and lead systems, such as biphasic shocks using endocardial defibrillating electrodes, is unknown. METHODS: Twenty consecutive patients undergoing testing and permanent implant using an Endotak lead system with a biphasic device were included in the study. In each patient the defibrillation threshold was determined delivering biphasic pulses with the distal coil as the cathode and the proximal coil as the anode during the positive phase and with the polarity reversed. The initial electrode polarity tested was chosen randomly. The defibrillation threshold was defined as the lowest pulse amplitude that effectively terminated ventricular fibrillation induced with 60-Hz alternating current. For each biphasic pulse peak voltage, pulse duration, resistance, and stored energy were recorded. RESULTS: Of the 20 patients, 12 (60%) had lower defibrillation threshold when the proximal coil was negative, whereas only 2 patients had a lower defibrillation threshold when the distal coil was negative. In four patients a subcutaneous patch would have been required if only the biphasic pulse with the distal coil as negative had been tested. The mean stored defibrillation threshold energy was lower with the configuration using the proximal coil as cathode (16.3 +/- 8.8 J vs 21.5 +/- 11 J; P < 0.01). CONCLUSION: Change in the initial polarity of biphasic shocks may influence defibrillation efficacy and should, therefore, be assessed in each patient to achieve a more satisfactory safety margin and minimize the use of more invasive lead configurations.

Defibrillators, Implantable↗
PubMed1995

Efficacy of different treatment strategies for neurocardiogenic syncope.

OBJECTIVES: The purpose of this study was to evaluate the efficacy of different therapeutic approaches for patients with a history of syncope and positive head-up tilt testing. BACKGROUND: Head-up tilt testing has gained broad acceptance as a reliable diagnostic method for the assessment of patients with recurrent unexplained syncope. However, once the diagnosis is established, there is no consensus on the most appropriate treatment. In this respect, efficacy of drug therapy in preventing recurrence of symptoms in such patients is not entirely clear, and controversies exist regarding the need to confirm the effects of pharmacological interventions. METHODS: Clinical follow-up was obtained in 303 patients with a history of syncope and positive head-up tilt testing. After the diagnostic head-up tilt, patients were assigned to different therapeutic approaches according to their preference or logistic impediments. Of 303 patients, 44 received empiric therapy, 210 were treated with medications proven effective during repeated head-up tilt testing, and 49 refused or discontinued medical therapy. The three groups were similar with regard to age, sex, and clinical presentation. The mean follow-up was 2.8 +/- 1.8 years. Among the patients treated according to head-up tilt guided therapy, 130 were on beta blockers, 35 on theophylline, 10 on ephedrine, 31 on disopyramide, and 4 on miscellaneous regimens. Empiric treatment consisted of beta blockers in 37 of 44 patients and other drugs in the remaining patients. RESULTS: During the follow-up, recurrence of symptoms was experienced in 12 (6%) of the 210 patients receiving the head-up tilt guided therapy, 16 (36%) of 44 in the empiric therapy group, and 33 (67%) of 49 in the no therapy group. Recurrence of symptoms in patients on empiric or no therapy was significantly more frequent as compared to the head-up tilt guided therapy group (P < 0.01). CONCLUSIONS: In patients with unexplained syncope and positive upright tilt testing, therapeutic strategies identified on the basis of response during head-up tilt have a more positive impact on the recurrence of symptoms during follow-up.

Adolescent↗
PubMed1995

Sensing failure in a tiered therapy implantable cardioverter defibrillator: role of auto adjustable gain.

Implantable cardioverter defibrillators have an established role in the management of life-threatening tachyarrhythmias. These devices use sophisticated sensing circuitry to detect and promptly treat a vast majority of these arrhythmias. However, they are not foolproof. We report one case where the device failed to sense every other QRS complex during induced ventricular fibrillation due to marked electrical alterans. Thus, undersensing can be a potentially fatal problem despite the use of auto adjustable gain.

Aged↗
PubMed1995

Radiofrequency catheter ablation of multiple morphologies of ventricular tachycardia by targeting a single region of the left ventricle.

INTRODUCTION: As treatment options for ventricular tachycardia (VT) continue to evolve, the use of radiofrequency catheter ablation is rapidly expanding. However, in the presence of multiple morphologies of VT, achieving successful results may seem less likely. We report two patients with multiple morphologies of VT who underwent successful radiofrequency ablation by application of radiofrequency energy to a single region in the left ventricle. METHODS AND RESULTS: Two patients, each without any apparent cardiac dysfunction and a history of documented VT, were referred to our institution for further management. They underwent an electrophysiologic study and were found to have easily inducible VT, of three morphologies in one patient and two in the other. Using a transaortic approach, left ventricular mapping was performed for detecting a site with presystolic potentials, earliest ventricular activation, or both. Application of radiofrequency energy to a single area in the left ventricle resulted in the elimination of all previously inducible VT in each patient. CONCLUSION: VTs with distinctly different morphologies can occur in patients with no detectable structural heart disease. These VT circuits may share a common pathway and, therefore, may readily be amenable to therapy with radiofrequency catheter ablation.

Adult↗
PubMed1995

Cardiac pacing during neurocardiogenic (vasovagal) syncope.

Head-up tilt testing is increasingly being used as a diagnostic modality in patients with unexplained syncope who are thought to have neurocardiogenic (vasovagal) mechanisms of syncope. Although large-scale placebo-controlled trials are still awaited, pharmacologic therapy is usually effective in preventing syncope or presyncope in this patient population. However, the role of permanent pacemaker therapy remains controversial. Because hypotension is usually associated with paradoxical bradycardia and occasionally asystole, it has been argued that permanent pacemaker therapy may be useful in preventing syncope and, thus, injury, in the so-called "malignant vasovagal cardioinhibitory response" in which the onset of syncope is thought to be abrupt. The onset of hypotension, however, usually precedes bradycardia during neurocardiogenic syncope, and pacing may thus not prevent syncope or presyncope in these patients. The role of cardiac pacing in patients with neurocardiogenic syncope is reviewed.

Animals↗
PubMed1995

Catheter ablation of the left bundle branch for the treatment of sustained bundle branch reentrant ventricular tachycardia.

Sustained Bundle Branch Reentrant VT. Radiofrequency catheter ablation of the left bundle branch (LBB) was attempted in a patient with sustained bundle branch reentry. During sinus rhythm, the QRS had a complete LBB block pattern, and the LBB was activated retrogradely (transseptal). Ablation of the LBB eliminated inducibility of the tachycardia, while the QRS complex and the duration of the HV interval (70 msec) remained unchanged. Successful ablation of the LBB eliminated bundle branch reentry and yet maintained the anterograde conduction properties of the His-Purkinje system, obviating implantation of a permanent pacemaker.

Aged↗
PubMed1995

Posteroseptal accessory pathways: an overview of anatomical characteristics, electrocardiographic patterns, electrophysiological features, and ablative therapy.

First, the posteroseptal region of the heart is probably the most complex area among those that harbor AV accessory fibers and a firm grasp of the anatomical characteristics of this region may facilitate achieving a successful AP ablation. Second, there is no sharp demarcation between the posteroseptal area and its surrounding regions including mid-septal, left posterior paraseptal, and right posterior paraseptal locations. Therefore, there are some inevitable overlaps between the electrocardiographic and electrophysiological features of APs located in the posteroseptal region and those areas immediately adjacent to it. Third, in the vast majority of cases, successful ablation can be achieved using a right atrial approach. Therefore, dividing posteroseptal APs into right- or left-sided pathways may only be useful for describing their ECG or electrophysiological characteristics with little or no value in predicting the site of successful ablation. Fourth, it seems advisable to attempt efforts to induce functional bundle branch block during orthodromic tachycardia and assess its effect on the VA interval. Ventriculoatrial interval prolongation due to right bundle branch block strongly favors a right free-wall or anteroseptal AP location. Prolongation of the VA interval by 30 msec or less in response to left bundle branch block is compatible with a posteroseptal location. In this situation, the mapping and ablative efforts should primarily be focused on the right atrial approach, including the terminal coronary sinus. If left bundle branch block causes VA interval lengthening of 30 msec or greater, the AP is most likely in the left free-wall region, including the posterior paraseptal area. Finally, the presence of APs having an intimate relationship with the middle cardiac (posterior interventricular) vein or the coronary sinus pouch, although exceedingly uncommon, should be considered in difficult cases in which radiofrequency applications to the conventional posteroseptal locations are unsuccessful. Such cases may require coronary sinus venography for better visualization and precise mapping of the terminal sinus complex.

Arrhythmias, Cardiac↗
PubMed1995

Catheter ablation in supraventricular tachycardia.

The evolution of catheter ablation for the treatment of supraventricular tachycardias represents a major advance in the management of cardiac arrhythmias. Excellent results in the majority of patients undergoing the procedure, together with a low rate of early complications and a brief hospitalization, make catheter ablation a highly cost-effective permanent cure. At present, however, its place in relation to alternate therapies in the management of supraventricular tachycardias has not been clearly established owing to unresolved risk-benefit issues. Continuing technical advances will likely enable catheter ablation to be successfully applied to a broader range of cardiac arrhythmias.

Anti-Arrhythmia Agents↗
PubMed1995

Renal failure in acute pancreatitis.

Twenty six (7.3%) of a total of 356 patients with acute renal failure were found to have acute pancreatitis as the primary disease. Seventeen (65.4%) of them were males. Their mean age was 35.6 years. Clinically epigastric pain and tenderness were seen in all (100%); nausea vomiting (73%), low grade fever (50%), left sided pleural effusion (38.4%), haemopericardium (26.9%), shock (26.9%), pseudocyst (19.3%) and adult respiratory distress syndrome (7.6%) were the other major presenting features. Serum amnylase (100%), lipase (53.8%), triglycerides (53.8%) and blood sugar (38.5%) were raised in majority whereas serum calcium was detected to be below normal in 46.2% patients. Blood urea and serum creatinine were raised in all and hyperkalacmia was found in 50% patients. CT scan and USG abdomen showed bilateral enlarged kidneys (100%), pancreatic oedema (80.7%), necrosis of pancreas (19.3%) and pseudocyst (19.3%). Management included repeated peritoneal dialysis in all (100%) and surgical intervention in 53.8% patients with severe necrotising and haemorrhagic pancreatitis. All patients recovered from acute renal failure, but 26.9% patients expired due to complications of acute pancreatitis other than acute renal failure.

Acute Disease↗
PubMed1994

Feasibility of concomitant implantation of permanent transvenous pacemaker and defibrillator systems.

In 17 patients (14 men and 3 women aged 69 +/- 10 years), a transvenous pacemaker was implanted before (8 patients), following (7 patients), or simultaneously (2 patients) with the insertion of a transvenous defibrillator. Indications included malignant ventricular arrhythmias and symptomatic bradycardia in all patients. All patients had structural heart disease. All pacemakers were non-programmable bipolar, either single chamber (n = 7) or dual chamber (n = 10). Eleven pacemakers were rate responsive. The Transvene system was implanted in 7 patients (Pacer-Cardioverter-Defibrillator in 6 patients and the Cadence defibrillator in 1). The Endotak lead system was implanted in 10 patients (Ventak in 7 patients and the Cadence in 3). The mean defibrillation threshold was 16 +/- 5 J. Repositioning of the pacemaker leads eliminated undersensing of ventricular fibrillation by the defibrillator, which occurred during asynchronous pacing in 2 patients. During a mean follow-up of 11 +/- 6 months, 2 patients died because of pump failure and 7 patients received defibrillator therapy for ventricular arrhythmias. No significant complications were noted. Successful concomitant implantation of transvenous pacemakers and defibrillators was thus accomplished in 17 patients, which suggests that insertion of a second transvenous device can be safely accomplished.

Adult↗
PubMed1994

Rhodopsin kinase: studies on the sequence of and the recognition motif for multiphosphorylations.

Peptides of 10-12 amino acids in length, which overlapped with the sequence of the last 20 amino acids in the C-terminal tail of rhodopsin, were synthesized and used as substrates for rhodopsin kinase. In all cases the phosphorylation of the peptides was found to be greatly stimulated (> 20-fold) by the presence of light-activated rhodopsin (Rho*). The incorporation of 32P at seven Ser/Thr residues that are the potential sites of phosphorylation was quantified, and the results were analyzed in terms of two parameters. First, a global comparison of phosphorylation at each site was made when the propensity for the modification was found to be in the order: Ser 343 > Ser 338 > Thr 336 > Ser 334, Thr 342 > Thr 335, Thr 340. Second, the peptides were aligned on a hypothetical template with the residue to be phosphorylated occupying the P-position, and the manner in which the nature of the surrounding residues effected the phosphorylation was assessed. It was found that the optimal phosphorylation of the P-site Ser/Thr occurs if it has at least one residue on the amino side and five on the acyl side and also contains a neutral residue, preferably small (A, P, S, T) at the P+4 position.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1994

The phospho-opsin phosphatase from bovine rod outer segments. An insight into the mechanism of stimulation of type-2A protein phosphatase activity by protamine.

The vertebrate visual transduction system involves a cycle of phosphorylation and dephosphorylation of a transmembranous photoreceptor (rhodopsin). Upon illumination, the activated photoreceptor (metarhodopsin-II) is phosphorylated by a specific kinase on up to seven serine and threonine residues. A dephosphorylation process must then be undertaken to return the photoreceptor to its ground state. Initial work, along with studies using the rabbit skeletal muscle catalytic subunit of protein phosphatase 2A, indicated that the phosphatase responsible was a member of the type-2 family. The work has been further extended and using 1000 bovine retinae, the catalytic subunit and a holoenzyme form of phospho-opsin phosphatase were purified 2100-fold and 550-fold respectively. The stimulation of the activities of both these fractions with protamine sulphate and the inhibition by okadaic acid are consistent with the fact that these phosphatases belong to the type-2A family. Western blotting using a variety of specific antibodies established that the catalytic subunit (36 kDa, C subunit) was indeed of type 2A, while the holoenzyme was a heterotrimer comprising the preceding catalytic subunit complexed to two other polypeptides of 55 kDa (B subunit) and 65 kDa (A subunit), both of which were of alpha subtype; phospho-opsin phosphatase may thus be described as a trimeric enzyme containing the ABC subunits of type-2A protein phosphatase, i.e. PP2A1. The dephosphorylation of phospho-opsin by both fractions was found to be stimulated (4-8-fold) by the presence of protamine sulphate (250 micrograms/ml; 50 microM). However, when phospho-peptides corresponding to the C-terminal region of opsin were used, these were maximally dephosphorylated without requiring the presence of protamine; at equivalent concentrations of substrates the phospho-peptides were dephosphorylated (in the absence of protamine) at rates which were approximately equal to those obtained with phospho-opsin (in the presence of protamine). It was shown that type-1 phosphatases had little activity against these phospho-peptides. Furthermore, if phospho-opsin was treated with protamine, the activity of the phosphatase assumed an elevated level and was not significantly stimulated by the addition of exogenous protamine. This effect could be reversed by washing the protamine-treated substrate with 1 M NaCl, whence the protamine-dependent stimulation returned to normal levels. To this end, studies revealed that protamine was binding to the particulate substrate in a ratio of protamine/opsin of 0.7:1. The cumulative finding may be rationalised by suggesting that the effect of protamine is a substrate-directed phenomenon and a hypothetical mechanism for this effect is considered.

Amino Acid Sequence↗
PubMed1994

Mechanism of the acyl-carbon cleavage and related reactions catalyzed by multifunctional P-450s: studies on cytochrome P-450(17)alpha.

It is now well-known that conventional cytochrome P-450s catalyze hydroxylation reactions using an iron mono-oxygen species, the structure of which, as inferred from chemical model studies, may be drrepresented by the following canonical forms: FeV==O<-->(.+)FeIV==O<-->FeIV--O(.). Certain multifunctional P-450s, notably those involved in steroid biosynthesis, catalyze, in addition to hydroxylation reactions, an acyl-carbon cleavage process in which the participation of an iron peroxide intermediate, FeIII--OOH, has been suggested. However the possibility still exists that the C--C bond cleavage may also occur using the FeV==O species. We have scrutinized the chemical consequences of involving either an FeV==O or an FeIII--OOH species for five different C--C bond cleavage reactions. With respect to the status as well as the origin of hydrogen and oxygen atoms, in four of the examples the mechanism involving the FeV==O species makes the same prediction as that using the iron peroxide intermediate, that is, the incorporation of an atom of oxygen from O2 into acyl part of the cleaved fragment. The fifth example, however, involving the formation, with pig testes microsomes, of 17 alpha-hydroxyandrogen (androst-5-ene-3 beta,17 alpha-diol) from pregnenolone, presents an interesting contrast--in this case different outcomes are predicted by the two mechanisms. These possibilities have been experimentally evaluated using substrates stereo- and regiospecifically labeled with heavy isotopes and incubated with pig testes microsomes under either 16O2 or 18O2.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗