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Biomedical subjects

A Zaidi

Publications and source records attributed to A Zaidi.

At least 19 recordsLinked to original sources

The use of the Hilbert transform in ECG signal analysis.

This paper presents a new robust algorithm for QRS detection using the first differential of the ECG signal and its Hilbert transformed data to locate the R wave peaks in the ECG waveform. Using this method, the differentiation of R waves from large, peaked T and P waves is achieved with a high degree of accuracy. In addition, problems with baseline drift, motion artifacts and muscular noise are minimised. The performance of the algorithm was tested using standard ECG waveform records from the MIT-BITH Arrhythmia database. An average detection rate of 99.87%, a sensitivity (Se) of 99.94% and a positive prediction (+P) of 99.93% have been achieved against study records from the MIT-BITH Arrhythmia database. A detection error rate of less than 0.8% was achieved in every study case. The reliability of the proposed detector compares very favorably with published results for other QRS detectors.

Algorithms↗

Bilateral extracorporeal shock wave lithotripsy in a spinal cord injury patient with a cardiac pacemaker.

OBJECTIVES: To review the precautions to be observed before and during extracorporeal shock wave lithotripsy (ESWL) in spinal cord injury (SCI) patients with a cardiac pacemaker and the safety of bilateral ESWL performed on the same day. DESIGN: A case report of bilateral ESWL in a SCI patient with a permanent cardiac pacemaker. SETTING: The Regional Spinal Injuries Centre, Southport, the Lithotripsy Unit, the Royal Liverpool University Hospitals NHS Trust, Liverpool, and the Department of Cardiology, Manchester Royal Infirmary, Manchester, UK. SUBJECT: A 43-year-old male sustained a T-4 fracture and developed paraplegia with a sensory level at T-2. During the post-injury period, he developed episodes of asystole requiring implantation of a dual chamber (DDD) permanent pacemaker. Twenty-one months later, he developed a right ureteric calculus with hydronephrosis. A radio-opaque shadow was seen in the left kidney with no hydronephrosis. During right ureteric stenting, the ureteric stone was pushed into the renal pelvis. 1,500 shock waves were delivered to this stone on the right side, followed by ESWL to the left intra-renal stone with 1250 shock waves. RESULTS: The patient tolerated ESWL to both kidneys. The pacemaker was reprogrammed to a single chamber ventricular pacing mode at 30 beats per minute with a reduced sensitivity during lithotripsy. There were no untoward cardiac events during or after lithotripsy. The serum creatinine was 45 micromol/l before lithotripsy and 44 micromol/l two weeks after ESWL. CONCLUSION: SCI patients with a cardiac pacemaker may be able to undergo extracorporeal shock wave lithotripsy following temporary reprogramming of the pacemaker. Bilateral, simultaneous ESWL is safe in the vast majority of patients provided that there is no risk of simultaneous ureteric obstruction by stone fragments. However, it should be remembered that a decrease in renal function could occur following bilateral ESWL of renal calculi.

Adult↗

Physiological aspects of pig-to-primate renal xenotransplantation.

BACKGROUND: Few data exist on the physiological aspects of pig-to-primate renal xenotransplantation. METHODS: Use of organs transgenic for human decay accelerating factor has allowed assessment of the metabolic and hormonal functions of these xenografts. RESULTS: Porcine renal xenografts largely maintain plasma electrolyte homeostasis. An increase in proteinuria was detected that may result from graft injury. In contrast to allotransplantation a severe anaemia developed requiring recipient treatment with exogenous human erythropoietin. CONCLUSIONS: Our experience provides qualified encouragement for the likely physiological compatibility of pig and primate species, but identifies areas where a xenograft may not match the performance of an allograft.

Anemia↗

Antisense oligonucleotide suppression of Na(+)/Ca(2+) exchanger activity in primary neurons from rat brain.

An antisense (AS) oligodeoxynucleotide based on a conserved sequence in the three isoforms of the Na(+)/Ca(2+) exchanger (NCX) was used to decrease expression of this Ca(2+) transporter in primary neuronal cultures. Two AS oligo applications decreased NCX activity by approximately 40% within 12-24 h, and neither sense (S) or missense (MS) oligos altered NCX activity. The reduced NCX expression was confirmed by immunoblots and enzyme-linked immunosorbent assays (ELISAs). Resting [Ca(2+)](i) levels were 20% higher in AS-treated neurons and showed a slower return to baseline levels following activation of Ca(2+) influx by N-methyl-D-aspartate (NMDA). These results suggest that NCX plays a significant role in maintaining neuronal Ca(2+) homeostasis and in restoring baseline Ca(2+) levels following depolarization.

Animals↗

Long-term survival of nonhuman primates receiving life-supporting transgenic porcine kidney xenografts.

BACKGROUND: Recently, there has been a resumed interest in clinical xenotransplantation using pig organs. However, no data are available yet regarding the capacity of porcine organs to sustain the life of a primate beyond the first month. We have attempted to obtain long-term survival of nonhuman primates using human decay-accelerating factor (hDAF) transgenic pig organs and an immunosuppressive strategy particularly aimed at neutralizing the humoral component of the immune response. METHODS: hDAF transgenic or control kidneys were transplanted into 14 bilaterally nephrectomized cynomolgus monkeys (Macaca fascicularis) that underwent splenectomy and were immunosuppressed with cyclosporine A, cyclophosphamide, and steroids. All animals also received recombinant erythropoietin. Postoperatively, the primates were monitored daily. Laboratory evaluations included serum biochemistry, hematology, and measurements of hemolytic antipig antibodies. To assess the role of splenectomy in the control of humoral response, historical data were also used from a group of monkeys (n=7) that received the same immunosuppressive regimen and an hDAF transgenic porcine kidney but did not have splenectomy or receive recombinant erythropoietin. RESULTS: This immunosuppressive approach obtained the longest survival time (78 days) described to date of a primate receiving a life-supporting porcine renal xenograft. Furthermore, four of nine animals in this series survived for 50 days or more. Most biochemical measurements in this study (including plasma urea, creatinine, sodium, and potassium concentrations) remained within normal ranges for several weeks in all of the longest-surviving animals. CONCLUSIONS: Normalization of renal function (urea and creatinine) in primate recipients of porcine renal xenografts suggests that pig kidneys may be suitable for future clinical xenotransplantation. Additional immunosuppressive approaches, specifically designed to prevent humorally mediated immunological damage, should be explored to further prolong survival of primates that have received porcine xenografts.

Animals↗

Geographic variation of HIV infection in childbearing women with syphilis in the United States.

OBJECTIVES: Substantial biologic and epidemiologic data indicate the importance of syphilis as a potential cofactor for sexual transmission of HIV infection, but few detailed data exist on the geographic covariation of these two important sexually transmitted infections. DESIGN: HIV prevalence in childbearing women and primary and secondary (P&S) syphilis data from 29 states were examined to explore the importance of the epidemiology of syphilis as a factor in facilitating HIV transmission. METHOD: The spatial relationship between P&S syphilis and HIV infection in the health districts of 29 states was analyzed and adjusted for demographic and socioeconomic factors such as racial composition, income, housing, education levels, and access to medical services using the 1990 US census, and geographic location. RESULTS: In 29 states and the District of Colombia, 448 health districts, representing more than 75% of the US population, reported HIV prevalence rates for mothers' district of residence. The HIV seroprevalence ranged from 0 to 1258/10 000 in these health districts. The incidence of P&S syphilis from 1984-1994 in these districts ranged from 0 to 87/100 000. The P&S syphilis incidence was positively associated with the prevalence of HIV infection among childbearing women (P < 0.0001). CONCLUSIONS: Syphilis that persists in communities in the United States appears to represent a 'sentinel public health event' reflecting risk for sexual HIV transmission. These findings, along with other biologic and epidemiologic information, reinforce the importance of syphilis as an indicator for targeting HIV prevention efforts generally, as well as syphilis control as a specific HIV-prevention strategy.

Confounding Factors, Epidemiologic↗

Misdiagnosis of epilepsy: many seizure-like attacks have a cardiovascular cause.

OBJECTIVES: We sought to investigate the value of cardiovascular tests to diagnose convulsive syncope in patients with apparent treatment-resistant epilepsy. BACKGROUND: As many as 20% to 30% of epileptics may have been misdiagnosed. Many of these patients may have cardiovascular syncope, with abnormal movements due to cerebral hypoxia, which may be difficult to differentiate from epilepsy on clinical grounds. METHODS: Seventy-four patients (33 men, mean age 38.9 +/- 18 years [range 16 to 77]) who were previously diagnosed with epilepsy were studied. Inclusion criteria included continued attacks despite adequate anticonvulsant drug treatment (n = 36) or uncertainty about the diagnosis of epilepsy, on the basis of the clinical description of the seizures (n = 38). Each patient underwent a head-up tilt test and carotid sinus massage during continuous electrocardiography, electroencephalography and blood pressure monitoring. Ten patients subsequently underwent long-term electrocardiographic (ECG) monitoring with an implantable loop recorder. RESULTS: In total, an alternative diagnosis was found in 31 patients (41.9%), including 13 (36.1%) of 36 patients taking an anticonvulsant medication. Nineteen patients (25.7%) developed profound hypotension or bradycardia during the head-up tilt test, confirming the diagnosis of vasovagal syncope. One other patient had a typical vasovagal reaction during intravenous cannulation. Two patients developed psychogenic symptoms during the head-up tilt test. Seven patients (9.5%) had significant ECG pauses during carotid sinus massage. In two patients, episodes of prolonged bradycardia correlated precisely with seizures according to the insertable ECG recorder. CONCLUSIONS: A simple, noninvasive cardiovascular evaluation may identify an alternative diagnosis in many patients with apparent epilepsy and should be considered early in the management of patients with convulsive blackouts.

Adolescent↗

Haemodynamic effects of increasing angle of head up tilt.

OBJECTIVE: To investigate the haemodynamic effects of varying the angle of head up tilt. METHODS: 20 healthy subjects (12 female, eight male; mean (SD) age 33.6 (8.4) years) underwent head up tilt for five minutes to each of four angles of tilt in random order, with a five minute rest period at the horizontal between each angle. Forearm blood flow was measured using intermittent occlusion mercury strain gauge plethysmography at two and five minutes. Subjects underwent continuous monitoring of heart rate, systolic blood pressure (SBP), and diastolic blood pressure (DBP) by Finapres and cardiac output and stroke volume by impedance cardiography. Each variable was measured at two and five minutes, averaged over the period of blood flow measurement. RESULTS: Every haemodynamic variable at each angle was significantly different from supine values. Head up tilt produced progressive increases in heart rate (11-21%), SBP (12-21%), and DBP (20-33%) with increasing tilt angle. However, although 45 degrees produced significantly less haemodynamic effect, there were no significant differences for angles between 60 degrees and 90 degrees. Cardiac output fell on head up tilt by 17-20% and stroke volume by 28-34%, but increasing tilt angle produced no significant additional reduction in cardiac output and stroke volume because of increases in heart rate and vasoconstriction. CONCLUSIONS: Angles < 60 degrees produce significantly less haemodynamic effects than steeper angles. Increasing tilt angle beyond 60 degrees produces no apparent additional effect on cardiac output or sympathetic tone. Increasing tilt angle beyond 60 degrees confers no additional orthostatic stress and may not affect the sensitivity and specificity of head up tilt testing as previously thought. Sixty degrees of tilt is a more practical angle for support of a syncopal patient and is recommended.

Adult↗

Effects of reactive oxygen species on brain synaptic plasma membrane Ca(2+)-ATPase.

The regulation of free intracellular calcium [Ca2+]i is altered in neurons from the aged brain, possibly due to reductions in the activity of Ca2+ transporters. The plasma membrane Ca(2+)-ATPase (PMCA) plays a critical role in Ca2+ homeostasis, and its kinetic properties change in aged rat brain. These changes could be due to oxidative modification of PMCA as a result of age-related chronic oxidative stresses. The present studies were undertaken to determine the sensitivity of the neuronal PMCA to in vitro exposure of synaptic plasma membranes (SPMs) to reactive oxygen species (ROS). We examined the effects of three oxidants including peroxyl radicals generated by azo-initiators, 2,2'-Azobis 2-amidinopropane dihydrochloride (AAPH) and 4,4'-Azobis 14-cyanovaleric acid (ACVA), hydrogen peroxide (H2O2), and peroxynitrite (ONOO-). Synaptic plasma membranes briefly exposed to these oxidants were analyzed for functional and structural alterations in PMCA. Although all three oxidants led to significant loss of PMCA activity, the effect of ONOO- was the most potent, followed by peroxyl radicals and H2O2. Kinetic analysis of PMCA activity after oxidant treatment showed decreases in Vmax without significant changes in K(act). Immunoblots revealed oxidant-induced cross-linking of PMCA molecules that were partially reversed under reducing conditions and completely reversed with addition of urea. The PMCA appears to be very sensitive to inhibition by ROS and hence may be a target of oxidative stress in the aging brain. Reduction in its activity may contribute to age-related alterations in neuronal [Ca2+]i regulation.

Age Factors↗

Accurate diagnosis of convulsive syncope: role of an implantable subcutaneous ECG monitor.

Convulsive syncope due to transient bradycardia is recognized as a cause of treatment-resistant seizures. However, the diagnosis may be difficult to make with conventional electrocardiographic devices if attacks are infrequent. We present a case of apparent epilepsy in which a new implantable electrocardiographic event recorder (the 'Reveal' insertable loop recorder) was used to show that attacks were caused by prolonged asystole of up to 36 s in duration. The insertable loop recorder may have an important role in the investigation of patients with treatment-resistant seizures, particularly where there is a strong suspicion of an underlying cardiac arrhythmia.

Adult↗

Head-up tilting is a useful provocative test for psychogenic non-epileptic seizures.

Differentiating psychogenic non-epileptic attack disorder (NEAD) from true epilepsy is difficult. This often results in a misdiagnosis and unnecessary and ineffective treatment. Prolonged EEG/video recording is the most sensitive tool for differentiating NEAD from epilepsy, but is costly and therefore limited in availability. Provocative tests, particularly the use of saline injection, can reduce the length of monitoring but give rise to ethical dilemmas. This study assesses the value of head-up tilt testing as a provocative test for NEAD. Twenty-one patients (17 female, mean age 34.6 +/- 11.5 years) with recurrent seizure-like episodes and a clinical diagnosis of NEAD were studied. Patients were tilted to 80( composite function )on an electric tilt table with footplate support for up to 45 minutes during continuous ECG, EEG and blood pressure monitoring. Seventeen patients (81%) experienced typical symptoms (non-epileptiform limb shaking in 15 patients, absence in one patient, myoclonic jerking in one patient) during head-up tilt without significant EEG abnormalities or haemodynamic changes. The mean time to onset of seizure-like activity was 13.2 +/- 11 minutes (range 0-31 minutes). No patients suffered injury or any other significant side-effect. Provocative testing using suggestion and head-up tilt is a sensitive tool for diagnosing NEAD and represents a safe, simple and inexpensive outpatient technique for investigating patients with suspected NEAD.

Adult↗

Patients view of the anaesthetist in a developing country.

OBJECTIVE: The objective of this study was to assess patients regarding their knowledge and perception of the anaesthetists' role in patient care in a developing country. SETTING: The audit was conducted at the Aga Khan University Hospital, Karachi. METHODS: Two hundred surgical and 102 medical out-patients were included in the audit prospectively who filled a detailed questionnaire. RESULTS: Fifty-six percent of the patients knew that anaesthetists were medically qualified but only 20% and 27% had an idea about their role in the intraoperative and immediate postoperative period. 14.6% were aware of the anaesthetists role outside the operating room. No difference was observed between the two groups of patients except that a higher percentage of surgical patients were interested in having more information regarding anaesthesia and wanted to choose their anaesthetist if the need arose. Gender difference was observed in answer to two questions only. A higher percentage of males know the role of anaesthetist in the recovery room whereas a greater number of females who had surgery before remembered their anaesthetist postoperatively. CONCLUSION: The results of this audit show a poor perception of the anaesthetists role both inside and outside the operating room. Although public knowledge surveys have been carried out in developed countries there is a pressing need to repeat these in developing countries since the image as perceived by public may have a direct bearing on the recruitment of young doctors into an already shortage specialty in these less affluent countries.

Anesthesia↗

Decrease in Ca-ATPase activity in aged synaptosomal membranes is not associated with changes in fatty acyl chain dynamics.

We have examined lipid peroxidation (LPO) and fatty acid acyl chain dynamics in synaptosomal membranes isolated from aged rat (Fischer 344 x Brown Norway F1 hybrids) brains, correlating these results with measurements of enzymatic activity of the synaptic plasma membrane Ca2(+)-ATPase (PMCA). Calcium-dependent ATPase activity in these membranes exhibits progressive decreases with a maximal loss of activity with age of approximately 35%. The sensitivity of this membrane-bound ion transporter to the lipid composition of the surrounding membrane, as well as the high abundance of oxidatively sensitive polyunsaturated fatty acyl chains in synaptosomal membranes, suggests that this age-related loss in catalytic turnover may result from LPO-mediated protein modification and/or changes in the physical structure of the bilayer. However, high-performance liquid chromatography analysis of 2,4-dinitrophenylhydrazone derivatives reveals no significant age-related increases in the content of reactive aldehydes (malondialdehyde, formaldehyde, acetaldehyde or acetone) which comprise breakdown products of lipid peroxidation. Electron paramagnetic resonance measurements employing 5- and 12-stearic acid spin labels with the nitroxide reporter groups at two depths in the bilayer were used to assess the fatty acyl chain dynamics (fluidity) of synaptosomal membranes. The resulting spectra demonstrate anisotropic lipid dynamics of two populations of lipids, i.e. lipids in direct association with membrane proteins (boundary lipids) and bulk lipids that do not directly associate with proteins. The nanosecond dynamics of both lipid populations is unaltered with age indicating that any compositional changes occurring with age are insufficient to result in alterations in bilayer fluidity relevant to PMCA activity. Thus, the observed age-related decline in PMCA activity may be explained by direct modification of membrane protein.

Aging↗

Sensitivity of the synaptic membrane Na+/Ca2+ exchanger and the expressed NCX1 isoform to reactive oxygen species.

Two plasma membrane proteins, the Na+/Ca2+ exchanger (NCX) and the Ca2+-ATPase, are major regulators of free intraneuronal Ca2+ levels as they are responsible for extrusion of Ca2+ from the intracellular to the extracellular medium. Because disruption of cellular Ca2+ regulation plays a role in damage occurring under conditions of oxidative stress, studies were conducted to assess the sensitivity of the NCX to reactive oxygen species (ROS). Exchanger activity in brain synaptic plasma membranes and in transfected CHO-K1 cells was inhibited following brief exposure to the peroxyl radical generating azo initiator 2,2'-azobis(2-amidinopropane)dihydrochloride (AAPH) and to peroxynitrite. Incubation with hydrogen peroxide did not alter NCX activity, even at 800 microM concentration. In CHO-K1 cells transiently transfected with the NCX1 isoform of the exchanger, AAPH treatment decreased the maximal transport capacity (Vmax), whereas the K(act) remained unchanged. Peroxynitrite led to an increase in K(act) with no change in Vmax. Loss of activity following exposure to either AAPH or peroxynitrite was associated with the formation of high molecular weight aggregates of NCX, and AAPH also caused fragmentation of the exchanger protein. These findings suggest that the NCX is sensitive to biologically relevant ROS and could be involved in the loss of Ca2+ homeostasis observed under oxidative stress.

Amidines↗