Search PubMed⌕ Search

Biomedical subjects

M Akhtar

Publications and source records attributed to M Akhtar.

At least 91 records · Page 5Linked to original sources
PubMed1997

Defibrillation efficacy of commercially available biphasic impulses in humans. Importance of negative-phase peak voltage.

BACKGROUND: Recent studies have shown that specifically shaped biphasic waveforms can lower energy requirements for ventricular defibrillation. We prospectively compared the defibrillation efficacy of three different biphasic wave shapes incorporated in three commercially available implantable defibrillators. The results led to the development of a second protocol in which the importance of negative-phase peak voltage and duration was investigated. METHODS AND RESULTS: Defibrillation threshold (DFT) testing using different biphasic waveforms was performed randomly on 42 patients undergoing implantation of a cardioverter-defibrillator for ventricular arrhythmias. In 23 patients (group 1), 3 waveforms were tested: a CPI waveform with 60% positive-phase (P1) tilt and 50% negative-phase (P2) tilt, a Medtronic waveform with 65% fixed tilt in both P1 and P2, and a Ventritex waveform with 60% P1 tilt and a P2 leading edge voltage equal to half of the P1 trailing edge voltage. In 19 patients (group 2), 3 biphasic waveforms with equal P1 tilt at 65% but shorter P2 duration or smaller P2 peak voltage were tested. The Endotak C 60 series lead system (CPI) was used in 11 patients in group 1 and 10 patients in group 2. A Transvene lead system (Medtronics) was used in the remaining patients. Stored energy required for defibrillation was significantly lower with the CPI waveform compared with the Ventritex waveform. In group 2, energy requirements were significantly increased for the waveform with a smaller P2 peak voltage, whereas a short P2 duration did not influence defibrillation success. CONCLUSIONS: Our results suggest that specifically shaped biphasic waveforms delivered from commercially available devices can affect energy requirements for defibrillation. More importantly, the amplitude of the P2 peak voltage may be a more critical determinant than the P2 duration for defibrillation success of biphasic waveforms in humans.

Aged↗
PubMed1997

Efficacy of the implantable cardioverter-defibrillator in the elderly.

OBJECTIVES: We sought to assess the effect of advanced age on the outcome of patients with an implantable cardioverter-defibrillator (ICD). BACKGROUND: ICDs are effective in preventing sudden cardiac death in susceptible patients, but their beneficial effect on survival is attenuated by the high rate of nonsudden cardiac death in those treated. Although advanced age is an important variable in determining cardiovascular mortality, its impact on the outcome of patients with an ICD has been inadequately studied. METHODS: We performed multivariate analysis of a data base consisting of 769 consecutive patients with an ICD. Seventy-four patients > or = 75 years old at ICD implantation (Group 1) were compared with the remaining 695 patients (Group 2). RESULTS: The two groups were similar in clinical presentation, left ventricular function and gender distribution. The mean follow-up time was 29 and 42 months, respectively, for patients in Group 1 and Group 2. Actuarial survival at 4 years was 57% in Group 1 versus 78% in Group 2 (p = 0.0001). This difference was primarily due to a higher rate of nonsudden cardiac death in Group 1. On multivariate analysis, age > or = 75 years, New York Heart Association functional class III, left ventricular ejection fraction < 30% and appropriate shocks during follow-up were independently associated with increased mortality (odds ratio 3.56, 1.8, 1.6 and 1.39, respectively). CONCLUSIONS: Among patients with similar functional class and ejection fraction, the mortality risk is increased threefold in those > or = 75 years old at the time of ICD implantation. Extrapolation of results from younger patients is likely to overestimate ICD benefit in the elderly.

Age Factors↗
PubMed1997

The mutation T315A in Candida albicans sterol 14alpha-demethylase causes reduced enzyme activity and fluconazole resistance through reduced affinity.

Sterol 14alpha-demethylase (P45051) is the target for azole antifungal compounds, and resistance to these drugs and agrochemicals is of significant practical importance. We undertook site-directed mutagenesis of the Candida albicans P45051 heterologously expressed in Saccharomyces cerevisiae to probe a model structure for the enzyme. The change T315A reduced enzyme activity 2-fold as predicted for the removal of the residue that formed a hydrogen bond with the 3-OH of the sterol substrate and helped to locate it in the active site. This alteration perturbed the heme environment, causing an altered reduced carbon monoxide difference spectrum with a maximum at 445 nm. The changes also reduced the affinity of the enzyme for the azole antifungals ketoconazole and fluconazole and after expression induced by galactose caused 4-5-fold azole resistance in transformants of S. cerevisiae. This is the first example of a single base change in the target enzyme conferring resistance to azoles through reduced azole affinity.

Amino Acid Sequence↗
PubMed1997

Interaction of human CYP17 (P-450(17alpha), 17alpha-hydroxylase-17,20-lyase) with cytochrome b5: importance of the orientation of the hydrophobic domain of cytochrome b5.

Human CYP17 (P-450(17alpha), 17alpha-hydroxylase-17,20-lyase)-catalysed side-chain cleavage of 17alpha-hydroxyprogestogens into androgens is greatly dependent on the presence of cytochrome b5. The native form of cytochrome b5 is composed of a globular core, residues 1-98, followed by a membrane insertable C-terminal tail, residues 99-133. In the present study the abilities of five different forms of cytochrome b5 to support the side-chain cleavage activity of CYP17 were compared. The five derivatives were: the native pig cytochrome b5 (native pig), its genetically engineered rat counterpart (core-tail), the soluble core form of the latter (core), the core with the secretory signal sequence of alkaline phosphatase appended to its N-terminal (signal-core) and the latter containing the C-terminal tail of the native rat protein (signal-core-tail). When examined by Edman degradation and MS, the engineered proteins were shown to have the expected N-terminal amino acid sequences and molecular masses. The native pig was found to be acetylated at the N-terminal. The native pig and core-tail enzymes were equally efficient at enhancing the side-chain cleavage activity of human CYP17 and the signal-core-tail was 55% as efficient. The core and signal-core constructs were completely inactive in the aforementioned reaction. All the five derivatives were reduced to varying degrees by NADPH:cytochrome P-450 (NADPH-P450) reductase and the relative efficiencies of this reduction were reminiscent of the behaviour of these derivatives in supporting the side-chain cleavage reaction. In the side-chain cleavage assay, however, NADPH-P450 reductase was used in large excess so that the reduction of cytochrome b5 derivatives was not rate-limiting. The results highlight that productive interaction between cytochrome b5 and CYP17 is governed not only by the presence of a membrane insertable hydrophobic region on the cytochrome b5 but also by its defined spatial orientation at the C-terminal.

Acetaldehyde↗
PubMed1997

Recoverin inhibits the phosphorylation of dark-adapted rhodopsin more than it does that of bleached rhodopsin: a possible mechanism through which rhodopsin kinase is prevented from participation in a side reaction.

In its resting state rhodopsin kinase is present in an inactive from and is activated after interaction with light-activated rhodopsin (Rho*). The activated rhodopsin kinase then phosphorylates Rho* but is also able to catalyse the phosphorylation of dark-adapted rhodopsin. A consequence of the latter behaviour of the activated kinase is that at low levels of bleach a large number of phosphoryl groups are incorporated per mol of Rho*. Recoverin- and Ca2+-dependent inhibition of rhodopsin kinase was found to be inversely related to the extent of bleaching; the lower the fraction of rhodopsin bleached, the greater the inhibition. The IC50 of recoverin is approx. 1 microM at a 0.2% level of bleach and about 5 microM in a fully bleached sample. The inhibitory effect of recoverin was studied separately on the phosphorylation of rhodopsin and Rho*. The formation of phosphorylated rhodopsin was inhibited 4.5-fold more strongly than that of phosphorylated Rho*. These results are interpreted to suggest that one of the roles of the recoverin-dependent regulation of the activity of rhodopsin kinase is to prevent the enzyme from participating in the unwanted phosphorylation of dark-adapted rhodopsin, directing it to fulfil its 'correct' function of quenching the transduction activity of Rho*.

Calcium↗
PubMed1997

The Heidelberg classification of renal cell tumours.

This paper presents the conclusions of a workshop entitled 'Impact of Molecular Genetics on the Classification of Renal Cell Tumours', which was held in Heidelberg in October 1996. The focus on 'renal cell tumours' excludes any discussion of Wilms' tumour and its variants, or of tumours metastatic to the kidneys. The proposed classification subdivides renal cell tumours into benign and malignant parenchymal neoplasms and, where possible, limits each subcategory to the most commonly documented genetic abnormalities. Benign tumours are subclassified into metanephric adenoma and adenofibroma, papillary renal cell adenoma, and renal oncocytoma. Malignant tumours are subclassified into common or conventional renal cell carcinoma; papillary renal cell carcinoma; chromophobe renal cell carcinoma; collecting duct carcinoma, with medullary carcinoma of the kidney; and renal cell carcinoma, unclassified. This classification is based on current genetic knowledge, correlates with recognizable histological findings, and is applicable to routine diagnostic practice.

Humans↗
PubMed1997

Is it feasible to diagnose germ-cell tumors by fine-needle aspiration biopsy?

Fine needle aspiration biopsy is an extremely useful procedure for the diagnosis of germ cell tumors. Most of the subtypes can be easily recognized and differentiated from other subtypes. For difficult cases clinical pathologic correlation may be extremely helpful in establishing a precise diagnosis. Mixed germ cell tumors may cause some difficulty if one of the components is predominant. Immunohistochemistry may also play an important role in arriving at a definitive diagnosis.

Biopsy, Needle↗
PubMed1997

Evaluation and treatment strategies in patients at high risk of sudden death post myocardial infarction.

Over 50 percent of deaths in patients who survive an acute myocardial infarction are due to fatal ventricular tachyarrhythmias. Patients who survive an episode of sustained ventricular arrhythmia are at highest risk of recurrent cardiac arrest. Electrophysiologic studies have been found to be useful in guiding therapy and reducing mortality in these patients and in patients with syncope due to arrhythmic etiology. Evaluation and treatment of nonsustained ventricular tachycardia post infarction remains somewhat controversial. A recently published trial (MADIT), however, showed improved survival with an implanted defibrillator in patients with coronary disease and asymptomatic nonsustained ventricular tachycardia. Asymptomatic patients post infarction at high risk include those who have significant left ventricular dysfunction, late potentials, high-grade ventricular ectopy, and abnormal heart rate variability. These tests individually, however, have a low positive predictive accuracy. This, combined with the fact that antiarrhythmic drugs are frequently not effective and can be proarrhythmic, leaves the best treatment for these patients uncertain. It is known, however, that beta-adrenoreceptor blocking agents do reduce mortality after an acute myocardial infarction. Early studies have shown mixed results relating to sudden death and total mortality with amiodarone. To date, no other antiarrhythmic drug has shown benefit, while several have been shown to be harmful. Recent studies have also shown some beneficial effects of angiotensin-converting enzyme inhibitors, carvedilol, a third-generation beta-blocking agent with vasodilator properties, and the angiotensin II receptor antagonist losartan. However, their precise role in reducing sudden death needs to be defined further.

Anti-Arrhythmia Agents↗
PubMed1997

Idiopathic membranous nephropathy in identical twins.

Familial idiopathic membranous nephropathy is rarely reported, despite the striking immunogenetic association of the disease with certain HLA antigens. This report describes a pair of identical male twins who contemporaneously developed idiopathic membranous nephropathy. HLA typing was carried out in the twins and in almost all members of their family. Interestingly, HLA antigens that have been reported to be associated with idiopathic membranous nephropathy, especially DR3, were found not only in the twins, but in the other family members as well. Due to similarities between Heymann nephritis and human membranous nephropathy, we performed a search for anti-brush border and antipodocyte antibodies. The inability to detect these antibodies suggests that they were probably not involved in the pathogenesis of these cases.

Adult↗
PubMed1997

Catheter ablation for atrioventricular nodal reentrant tachycardia.

The current status of catheter ablation techniques for the management of atrioventricular nodal reentry tachycardia is outlined in this article. Some pertinent aspects of the atrioventricular nodal anatomy and physiology are discussed, to the extent that they are essential for understanding of the mechanism of this arrhythmia and the technique of catheter ablation.

Cardiac Pacing, Artificial↗
PubMed1997

Human herpesvirus-8/Kaposi's sarcoma-associated herpesvirus in organ transplant patients with immunosuppression.

Several recent studies have demonstrated Kaposi's sarcoma-associated herpes virus (KSHV), also known as putative human herpes virus-8 (HHV-8), DNA in various epidemiologic forms of Kaposi's sarcoma (KS), including AIDS-associated, classic, and endemic types. Risk of developing KS in non-HIV-infected immunosuppressed hosts, such as patients following solid organ transplantation, is also significantly higher compared to normal individuals. We have retrospectively evaluated 28 organ transplant patients with KS (23 cutaneous and five visceral) for the presence of KSHV genome by polymerase chain reaction (PCR) amplification of DNA isolated from formalin-fixed, paraffin-embedded archival tissue samples. 27/28 KS patients were positive for the presence of KSHV. In four KS patients, tissue samples with no histologic evidence of KS were also analysed for KSHV. No evidence of positivity in three samples was noted, but one patient had weak positive amplification products on DNA samples isolated from a gastric biopsy with chronic gastritis and lymph node with sinus histiocytosis. These data support the association of KSHV with KS developing in non-HIV-infected immunosuppressed patients, similar to other forms of KS, and suggest that KSHV may play a significant role in the development of all forms of KS.

Blotting, Southern↗
PubMed1997

Yield and complications in percutaneous renal biopsy. A comparison between ultrasound-guided gun-biopsy and manual techniques in native and transplant kidneys.

PURPOSE: To compare the yield and complications of ultrasound-guided gun-biopsy and manual Tru-Cut techniques in percutaneous renal biopsy. MATERIAL AND METHODS: A total of 448 biopsies were reviewed. They comprised 124 manual and 131 gun-biopsies in native kidneys, and 111 manual and 82 gun-biopsies in transplant kidneys. The gun-biopsies were performed under real-time ultrasound (US) guidance. The manual technique used US mainly for marking the position of the kidney. RESULTS: There was a significantly higher diagnostic yield and fewer complications in the gun-biopsy group. A total of 8 major complications were found, all in the manual group. CONCLUSION: Provided that the operator is experienced in US scanning, a switch from the manual technique to real-time US-guided gun-biopsy will result in the improvement of diagnostic accuracy together with a reduced risk of complications.

Adolescent↗
PubMed1997

Sarcomatoid renal cell carcinoma: the chromophobe connection.

Eleven cases of sarcomatoid renal cell carcinoma were studied to determine the relative frequency of various subtypes of renal cell carcinoma that may be associated with sarcomatoid transformation. The epithelial components in these tumors were subcategorized according to established histologic criteria into chromophobe carcinoma (n = 6 cases), clear cell carcinoma (n = 3), papillary carcinoma (n = 1), and indeterminate (n = 1). In nine cases, material was available for immunohistochemical and DNA ploidy studies. The sarcomatoid component in all cases showed positivity for epithelial membrane antigen cytokeratin, indicating an epithelial derivation of these cells. Staining for mesenchymal markers was mostly negative, except for vimentin, which reacted strongly in all cases. DNA ploidy studies using flow cytometry and cell image analysis provided very similar results. Five of five chromophobe sarcomatoid carcinomas showed hypodiploid cell lines in the epithelial areas, whereas the sarcomatoid components mostly showed aneuploid peaks. In the remaining cases, DNA ploidy pattern was more variable. These findings indicate that chromophobe carcinoma may be the most frequent epithelial component associated with sarcomatoid renal cell carcinoma.

Adult↗
PubMed1997

The effect of biphasic waveform tilt in transvenous atrial defibrillation.

Atrial defibrillation can be accomplished using low energy shocks and transvenous catheters. The biphasic waveform tilt required to achieve optimal atrial defibrillation thresholds (ADFTs) is, however, not known. The effect of single capacitor biphasic waveform tilt modification on ADFT was assessed in 20 patients. Following AF induction the defibrillation pulses were delivered between the catheters positioned in the coronary sinus and the right atrium. The single capacitor biphasic waveform shocks, delivered over the same pathways, consisted of 65% tilt (65/65 biphasic waveform) to produce an overall tilt of 88%, or 50% tilt (50/50 biphasic waveform) to produce an overall tilt of 75%. Although 65/65 biphasic waveform delivers more energy, the shorter duration 50/50 biphasic waveform reduced stored energy ADFT 21%, from 1.34 +/- 0.82 J with 65/65 biphasic to 1.06 +/- 0.81 J. These differences were not statistically significant. Nine patients had lower ADFT with 50/50 biphasic waveform while five patients had lower ADFT with 65/65 biphasic waveform. Equivalent reduction in ADFT was seen in the remaining six patients. The ADFT was 0.83 +/- 0.65 J when both tilts were considered. In conclusion, biphasic waveform tilt modification may affect the ADFT in an individual patient. The optimal biphasic waveform for ADFT is not known.

Adult↗
PubMed1997

Right side implant of the unipolar single lead defibrillation system.

The active can defibrillator has been designed for implantation in the left prepectoral region. Whether this system can be successfully implanted on the right side is unknown. We describe six cases in which placement of the unipolar single lead defibrillation system was successfully attempted in the right prepectoral region due to impediments on the left side. The mean age of the patients was 62 +/- 12 years. Five patients had ischemic heart disease and one idiopathic dilated cardiomyopathy. The endocardial defibrillation electrode was placed in the right ventricle through the right subclavian vein and positioned at the apex in two patients and in the septal position in four patients. Defibrillation threshold testing was performed using a step-up/step-down protocol beginning at 12 J with 3-J increments or decrements. Defibrillation threshold was defined as the lowest energy of the first shock able to terminate ventricular fibrillation. The generator models used were the Medtronic 7218C in 1 patient, the Medtronic 7219C in 3 patients, and the Ventritex Cadet 115 AC in 2 patients. The mean defibrillation threshold was 15 +/- 3 J. The defibrillation thresholds were retested at 1, 3, and 6 months, and showed no significant change in five patients but decreased from 15 J to 12 J in one patient. The presence of impediments on the left side should not preclude attempts to place the unipolar active can system in the right prepectoral region.

Aged↗
PubMed1997

The effect of polarity of the initial phase of a biphasic shock waveform on the defibrillation threshold of pectorally implanted defibrillators.

The effect of initial phase polarity on the DFT of two pectorally implanted biphasic ICDs was tested in a randomized, prospective manner at the time of implantation. Twenty-two consecutive patients with VT-VF who received either the Medtronic PCD 7219C Jewel device (10 patients) or PCD 7219D Jewel device (12 patients) were studied. DFT testing was performed in a standard step-down manner. Both initial phase polarities--initial defibrillation current flowing from active can/SVC coil +/- subcutaneous patch) to the RV coil (RV coil to active can/SVC (RV+)--were tested in random order. The mean DFT achieved with RV+ compared with RV-was lower for the 7219C patient group (6.6 +/- 3.1 vs 10.8 +/- 5.5 J; P = 0.007). A similar trend was observed for the 7219D group, though the difference did not reach statistical significance (12.0 +/ 4.0 vs 16.3 +/- 7.3 J; P = 0.07). Seven of the 10 patients in the 7219C group had a lower DFT with RV+, while the initial phase polarity made no difference in 3. In the 7219D group, 7 patients had a lower DFT using RV+, 2 patients had a lower DFT using RV-, and the initial phase polarity made no difference in 3. In conclusion, this study demonstrates that changing the polarity of the initial phase of a biphasic shock waveform can have a significant impact on the DFT achieved at the time of ICD implantation.

Aged↗