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Biomedical subjects

B R Reddy

Publications and source records attributed to B R Reddy.

At least 19 recordsLinked to original sources

Degradation of monocrotophos in soils.

The degradation of a widely used organophosphorus insecticide, monocrotophos (dimethyl (E)-1-methyl-2-methylcarbamoyl vinyl phosphate) in two Indian agricultural soils at two concentration levels, 10 and 100 microg g(-1) soil under aerobic conditions at 60% water-holding capacity at 28+/-4 degrees C was studied in a laboratory. The degradation of monocrotophos at both concentrations in black vertisol and red alfinsol soils was rapid accounting for 96-98% of the applied quantity and followed the first-order kinetics with rate constants (k) of 0.0753 and 0.0606 day(-1) and half-lives (t1/2) of 9.2 and 11.4 days, respectively. Degradation of monocrotophos in soils proceeded by hydrolysis with formation of N-methylacetoacetamide. Even three additions of monocrotophos at 10 microg g(-1) soil did not result in its enhanced degradation. However, there was cumulative accumulation of N-methylacetoacetamide in soils pretreated with monocrotophos to the tune of 7-15 microg g(-1) soil. Both biotic and abiotic factors were involved in degradation of monocrotophos in soils.

Agriculture↗

Interaction effects of insecticides on microbial populations and dehydrogenase activity in a black clay soil.

Three insecticides, monocrotophos, quinalphos, and cypermethrin, were applied at 0, 5, 10, and 25 microg g(-1) either singly or in combination to a black clay soil to investigate their effects on the soil microflora and dehydrogenase activity. All three insecticides significantly enhanced the proliferation of bacteria and fungi and the soil dehydrogenase activity even at the highest level of 25 microg g(-1). Monocrotophos or quinalphos in combination with cypermethrin at tested levels interacted significantly to yield additive, synergistic, and antagonistic responses toward bacteria and fungi and dehydrogenase activity in soil. Antagonistic interactions were more pronounced toward soil microflora and dehydrogenase activity when the two (monocrotophos or quinalphos + cypermethrin) insecticides were present together in the soil at highest level (25 + 25 microg g(-1)), whereas synergistic or additive responses occurred at lower level with the same combination of insecticides in soil.

Bacteria↗

Prospective evaluation of a microprocessor-assisted cardiac rhythm algorithm: results from one clinical center.

A new microprocessor-assisted cardiac rhythm algorithm (MAC-RHYTHM), based on median QRST subtraction from 10-second electrocardiographic (ECG) data, was prospectively tested on 10,761 ECGs acquired at one of three clinical centers. Atrial waves (P waves, atrial fibrillatory waves, and flutter waves) were detected from the median QRST-subtracted residual signals. Rhythm criteria were applied to the detected atrial waves and their temporal relation to QRS complexes for generating rhythm interpretations. Rhythm statements generated by MAC-RHYTHM were compared against the true rhythm of the ECGs as read by an experienced cardiologist. The results of prospective testing were compared with the results of an earlier retrospective testing using MAC-RHYTHM and a released commercial ECG analysis program on stored ECGs. The prospective results were very similar to the results of MAC-RHYTHM on retrospective data for all the rhythms examined (sinus rhythms, atrial fibrillation, atrial flutter, junctional rhythms, second degree atrioventricular blocks). For three of the abnormal rhythms, namely, atrial fibrillation, junctional rhythms, and second degree atrioventricular blocks, MAC-RHYTHM gave significantly higher sensitivity in both prospective (87.5%, 92.2%, and 80.8%, respectively) and retrospective (82.0%, 81.2%, and 79.6% respectively) testing than the released commercial ECG analysis program (65.0%, 39.6%, and 12.0% respectively). Similarly, for sinus rhythms, MAC-RHYTHM had significantly higher specificity (prospective, 91.0% and retrospective, 91.7%) than the released commercial program (86.5%). The specificity for the abnormal rhythms remained very high with MAC-RHYTHM (prospective, 99.4% to 99.7% and retrospective, 99.1% to 99.7%) compared to the released commercial program (99.0% to 99.9%). This prospective study also indicated that further work is needed to improve the detection of pacemaker spikes and the interpretation of paced rhythms in 10-second resting ECGs.

Arrhythmias, Cardiac↗

Late potential recognition by artificial neural networks.

Ventricular late potentials (LP's) are high-frequency low-amplitude signals obtained from signal-averaged electrocardiograms (ECG's) [SAECG's]. LP's are useful in identifying patients prone to ventricular tachycardia (VT), spontaneous or inducible during electrophysiology testing. A combination of self-organizing and supervised artificial neural network (ANN) models was developed to identify patients with a positive electrophysiology (PEP) test for inducible ventricular tachycardia from patients with a negative electrophysiology (NEP) test using LP's. We have added morphology information of vector magnitude waveform to original set of three time-domain features of LP's, which are total QRS duration (TQRSD), high-frequency low-amplitude signal duration (HFLAD), and root-mean-square voltage (RMSV). Pattern recognition results from an ANN model with this combination feature set are superior to the results from Bayesian classification model based on conventional three time-domain features of SAECG. In order to increase the robustness of the recognition, a filtered QRS offset point is randomly shifted +/- 8 ms to form a fuzzy training set, which was to simulate the possible error in detecting QRS offset point of filtered SAECG. We also found that nonlinear transformation through the hidden layer of developed ANN model could increase Euclidean distance between PEP and NEP patterns.

Algorithms↗

Analysis of interval measurements on CSE multilead reference ECGs.

As part of the International Electrotechnical Commission's (IEC) efforts to develop standards for interpretive electrocardiographs, electrocardiograms (ECGs) of the Common Standards of Electrocardiography (CSE) multilead measurement database were processed to (1) determine whether original ECG data would offer any advantage over cycle-repeated (artificial) ECGs and (2) compare the "clean" ECGs selected for interval measurement compliance testing (n = 100) with the remaining 25 "noisy" or nonsinus rhythm ECGs. Two sets of CSE measurement ECGs, namely, 125 original ECGs of the MO1 series and 125 artificial ECGs of the MA1 series were divided into 100 IEC-selected clean ECGs with good P and T waves and 25 noisy or nonsinus ECGs and processed for global wave duration and interval measurements (P duration, PR interval, QRS duration, and QT interval). The measured duration and interval values were compared against the CSE reference values (medians of referee values for 25 physician overread ECGs and medians of interpretive programs for the rest) to compute the measurement "differences". Also, the data of the median cardiac complex were evaluated for noise content. The original ECG data gave consistently smaller differences for all of the four measurements than the differences with the artificial ECG data. The noise levels in the median complexes formed from the original ECG data were significantly lower than the noise levels in the median complexes from the artificial ECG data. The noise levels in the medians of the 100 clean ECGs were lower than the noise levels in the medians of the 25 noisy ECGs for both the original and artificial ECG data.

Algorithms↗

Analysis of high-frequency signal-averaged ECG measurements.

Analysis of high frequency (150-250 Hz) in the signal-averaged electrocardiogram (SAECG) is one of the emerging methods for detecting vessel patency in acute myocardial infarction following thrombolytic therapy and angioplasty. Root-mean-square voltage (RMSV) of the filtered QRS has been used in earlier studies to detect reperfusion; however, previous analysis indicated that RMSV is sensitive to residual noise in the SAECG and errors in QRS delineation (onset/offset). A new measurement is proposed, high-frequency energy (HFQE), and the robustness of the RMSV and HFQE was evaluated for simulated errors in QRS delineation. In this study, two measures (RMSV and HFQE) were tested on 24 control subjects and 21 patients undergoing thrombolytic therapy. Results indicate that unfiltered QRS duration is more stable than filtered QRS duration for the control subjects and patients and that HFQE had less fluctuation than RMSV in thrombolytic therapy patients. In the control group, HFQE was sensitive to the amplitude variation of the filtered SAECG. Therefore, another new measurement is proposed high-frequency integral of absolute value (HFAV), for reducing the sensitivity to amplitude changes in the filtered SAECG. This new feature was tested on control subjects and was found to be more stable than HFQE. In the thrombolitic therapy group, HFAV provided similar information as HFQE. These three measurements-RMSV, HFQE, and HFAV-provide a comprehensive analysis of the high-frequency SAECG for detecting vessel patency and reocclusion. Relative merits of these measures need to be evaluated on a larger database of patients undergoing thrombolysis and angioplasty for acute myocardial infarction.

Angioplasty, Balloon, Coronary↗

The effect of prostaglandin E1 on liver adenine nucleotides and cytoplasmic enzymes in a porcine model of normothermic hepatic ischemia.

The liver has been judged relatively resistant to ischemia, but prolonged inflow occlusion at normothermic conditions can produce evidence of reversible or irreversible hepatocellular damage. Cytoprotective agents have been used both experimentally and clinically to afford extended viability of hepatocytes under reduced perfusion. One agent, prostaglandin E1, has been described clinically as effective in sustaining liver function under ischemic conditions. We have sought to verify this observation in an experimental model using prolonged normothermic inflow occlusion. Twenty miniature pigs were anesthetized and subjected to subtotal normothermic hepatic inflow occlusion (portal vein, hepatic artery, choledochal vessels) to allow for sufficient splanchnic decompression. Half of the animals received pretreatment with prostaglandin E1 (alprostadil) 500 micrograms intravenously. Inflow occlusion was maintained for 2 hours followed by reperfusion and killing 24 hours later. As a measure of functional preservation, the tissue adenine nucleotides adenosine monophosphate, diphosphate, and triphosphate (AMP, ADP, ATP) were measured in ischemic liver by freeze-clamping and high-performance liquid chromatography during occlusion and after reperfusion. Cytosolic enzyme determinations (aspartate transaminase, alanine transaminase, lactate dehydrogenase) were also made before occlusion and after reperfusion. As a possible indicator of cellular injury, blood ionized Ca++ was measured before inflow occlusion and after reperfusion. Although no difference was found in levels of AMP and ADP between prostaglandin E1 and control animals, ATP levels rose significantly higher during recovery in prostaglandin E1 animals at 60 minutes and 24 hours after reperfusion (13.97 +/- 1.29 and 13.60 +/- 0.91 mumoles/gm dry weight prostaglandin E1 vs. 9.25 +/- 0.97 and 9.80 +/- 0.85 mumoles/gm dry weight co control, P < .01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenine Nucleotides↗

Two identical copies of IS1246, a 1275 base pair sequence related to other bacterial insertion sequences, enclose the xyl genes on TOL plasmid pWW0.

Two identical direct repeats of a 1275 bp sequence, designated IS1246, encompass the xyl genes, which determine the catabolism of toluene, m- and p-xylenes to central metabolites, on the TOL catabolic plasmid pWW0. IS1246 has a terminal inverted repeat of 12 bp (5'GGGCACCTCGAA3') and contains a major open reading frame of 280 codons. This ORF shows significant homology with ORFs encoded by a number of bacterial insertion sequences from Bacteroides, Neisseria and Escherichia coli.

Amino Acid Sequence↗

Signal-averaged ECG parameters in cardiac normals using Frank lead system and Fourier transform filter and gender specific differences: a multicenter study.

There is only limited data on normal reference values for signal-averaged electrocardiograms (SAECGs) using Frank leads and fast Fourier transform filter (FFT). Furthermore, the influence of gender on reference values and their relation to body characteristics was only the subject of a few studies on small series of normals. One hundred eighty-five cardiac normals (85 women and 100 men) were examined in this multicenter study. The obtained SAECG values (mean +/- standard deviation) are as follows: filtered QRS duration (FQRSD) = 108.6 +/- 7.5 msec; low amplitude signal duration < 40 microV (LASD) = 30.4 +/- 8.4 msec; and root mean square voltage in the terminal 40 msec (RMSV) = 43.5 +/- 20.6 microV. Between men and women, significant differences were found in FQRSD (111.7 +/- 6.5 vs 105.0 +/- 7.0 msec, P < 0.001) and in RMSV (38.6 +/- 17.4 vs 49.4 +/- 22.7 microV, P < 0.001). No difference was observed for LASD. After normalizing the three SAECG parameters for body characteristics, FQRSD normalized for height was the only variable where gender differences were eliminated. For FQRSD and LASD the 90th percentile and for RMSV the 10th percentile are proposed as cut-off values. Only for the 90th percentile of FQRSD a clear difference between men and women was observed. The following gender specific normal values for SAECG, at 40-Hz high pass filtering, using Frank leads and an FFT filter are proposed: for males, FQRSD < 122 msec; for females, FQRSD < 115 msec; for both genders, LASD < 41 msec and RMSV > 20 microV.

Action Potentials↗

Slow response to vancomycin or vancomycin plus rifampin in methicillin-resistant Staphylococcus aureus endocarditis.

OBJECTIVE: To determine the median response time to therapy with vancomycin alone or with vancomycin plus rifampin in patients with methicillin-resistant Staphylococcus aureus (MRSA) endocarditis. DESIGN: Cohort analysis of a randomized study. SETTING: University medical center. PATIENTS: Forty-two consecutive patients with MRSA endocarditis were randomly assigned to receive either vancomycin (group I) or vancomycin plus rifampin (group II) for 28 days. MEASUREMENTS: Clinical signs and symptoms were recorded, and blood cultures were obtained daily to determine the duration of bacteremia. MAIN RESULTS: The median duration of bacteremia was 9 days (7 days for group I and 9 days for group II). The median duration of fever for all patients and for each treatment group was 7 days. Six patients failed therapy, including three patients who died 5, 6, and 9 days after therapy was started, respectively. The other three patients who failed therapy required valve surgery on days 2, 22, and 27, respectively. Although patients had sustained bacteremia, no unusual complications were seen in either treatment group, and most patients responded to continued antibiotic therapy. CONCLUSIONS: Slow clinical response is common among patients with MRSA endocarditis who are treated with vancomycin or vancomycin plus rifampin. Nevertheless, few complications appear to be related solely to this sustained bacteremia.

Adult↗

17 alpha-substituted analogs of estradiol for the development of fluorescent estrogen receptor ligands.

For the successful development of a high-affinity fluorophore-estradiol conjugate, the fluorophore must be attached to the estradiol molecule at a position that interferes least with its binding to the receptor. We have concentrated on 17 alpha substituents as models for fluorophore attachment, based on literature precedent and on our earlier work with small 17 alpha side chains. In this report, we describe syntheses and estrogen receptor binding affinities of 19 analogs of estradiol substituted in the 17 alpha position with larger side chains (of six to 11 carbons), some of which may be synthetically modified to link a fluorophore. These analogs were synthesized either by nucleophilic cleavage of estrone-17 beta-oxirane 3-benzyl ether and subsequent debenzylation (4 to 18), by cross-coupling of alkynes (21 to 24), by alkylation of 17 alpha-ethynylestradiol 3,17-bis(tetrahydropyranyl ether) and subsequent acidic hydrolysis (25 to 28), or by reacting estrone either with appropriate aryl/alkynyllithium reagents (29, 30, and 32) or with benzylmagnesium bromide (31). Relative binding affinities of these newly synthesized analogs were determined for estrogen receptor (rat uterus) using a standard competition assay. The results suggest that analogs with reduced mobility and/or more polarizable electron density in the side chain generally bind more strongly to the receptor. The relative affinities of several selected compounds were also determined in the presence of 4% dimethylformamide; some compounds bearing larger, nonpolar 17 alpha substituents showed dramatically improved affinities, while affinities for compounds with shorter nonpolar side chains remained largely unchanged. These binding affinity results should be useful in designing new high-affinity fluorescent ligands for the estrogen receptor.

Fluorescence↗

Pretreatment with the iron chelator desferrioxamine fails to provide sustained protection against myocardial ischaemia-reperfusion injury.

STUDY OBJECTIVE: The aim was to determine whether the potent iron chelator desferrioxamine, previously shown by our laboratory and others to cause acute limitation of infarct size, would provide sustained protection against myocardial ischaemia-reperfusion injury. DESIGN: Anaesthetised dogs underwent a 2 h transient coronary artery occlusion. After surgical preparation, each dog was randomised into one of two groups receiving either desferrioxamine or equivalent infusion of saline. Infusion of desferrioxamine was initiated 30 min before occlusion at an initial dose of 10 mg.kg-1 for the first hour of the protocol, followed by a maintenance dose of 1.5 mg.kg-1.h-1 throughout the remainder of the ischaemic period and the initial 4 h of reperfusion. The animals were reanaesthetised the following day and killed 20-24 h following reperfusion. Variables measured included heart rate and arterial pressures; regional myocardial blood flow; urinary iron content; and infarct size. In addition, % wall thickening in the ischaemic-reperfused myocardium was assessed by echocardiography in a limited number of animals. EXPERIMENTAL MATERIAL: 12 mongrel dogs weighing 22(SEM 4) kg were used, n = 6 in each group. MEASUREMENTS AND MAIN RESULTS: Both groups were equally and severely ischaemic during coronary artery occlusion. Desferrioxamine caused a modest and transient reduction in mean arterial pressure during the ischaemic episode, but had no effect on heart rate or myocardial blood flow. As expected, urinary iron content was significantly higher in treated animals v controls, at 465(SEM 107) v 55(23) micrograms, p less than 0.01, indicating that desferrioxamine effectively chelated free iron. However, it failed to exert a significant cardioprotective effect: infarct size did not differ between control and treated groups [54(4)% v 58(5)% of the myocardium at risk], and wall thickening was similar throughout occlusion and reperfusion in control and desferrioxamine treated animals. CONCLUSIONS: Despite substantial reduction in infarct size previously observed at 4 h following reflow with the same dose and regimen of desferrioxamine treatment, results of the present study indicate that desferrioxamine did not provide sustained protection against myocardial ischaemia-reperfusion injury. We therefore conclude that desferrioxamine delays--but does not prevent--myocyte necrosis in this canine model.

Animals↗

Developmental appearance of thrombospondin in neonatal mouse skeletal muscle.

Immunocytochemical localization of the adhesive glycoprotein thrombospondin made in comparison with other components of extracellular matrices shows its sequential appearance in the mouse muscle endomysium during postnatal development. Thrombospondin, absent at birth, in contrast to laminin, type IV collagen and fibronectin, is progressively detected during the first month of neonatal life in the whole muscle extracellular matrix. Immunoblotting of thrombospondin showed the appearance 14 days after birth of a band migrating at 180 kDa corresponding to thrombospondin. A fragment of thrombospondin at 110 kDa was already present at birth, as was also a lower molecular mass band at 70 kDa. Another band at 50 kDa also appeared during development in muscle extracts. Clonal muscle cells in culture were able to synthesize thrombospondin but only at the myotube stage, since little thrombospondin was detected at the myoblast stage. These data show a development regulation of thrombospondin expression in muscle which correlates with muscle differentiation.

Animals↗

Acute neurohormonal and hemodynamic response to a new peak III phosphodiesterase inhibitor (ICI 153,110) in patients with chronic heart failure.

Peak III phosphodiesterase (PDE) inhibitors have combined positive inotropic and vasodilator effects. We studied 10 patients with chronic heart failure during and after infusion of intravenous (i.v.) ICI 153,110, an investigational peak III PDE inhibitor. Maximum hemodynamic response for the group occurred after cessation of infusion at a lower plasma drug concentration. At maximum hemodynamic response, cardiac index (CI) increased (2.4 +/- 0.5 vs. 3.2 +/- 0.37 L/min/m2, p less than 0.05) with a decrease in mean arterial pressure (MAP 91 +/- 5 vs. 80 +/- 3 mm Hg, p less than 0.05), pulmonary capillary wedge pressure (PCWP 25 +/- 2 vs. 17 +/- 3.1 mm Hg, p less than 0.01), systemic vascular resistance (SVR 1,422 +/- 106 vs. 983 +/- 97 dynes.s.cm-5, p less than 0.05) and pulmonary vascular resistance (PVR 227 +/- 39 vs. 16 +/- 31 dynes.s.cm-5, p less than 0.05). During the infusion, plasma renin activity (PRA) decreased from 6.34 +/- 2.53 to 3.6 +/- 3 ng/ml/h (NS). The five patients with high baseline PRA had a significant decrease (11.2 +/- 2.5 vs. 5.4 +/- 1.67 ng/ml/h, p less than 0.01) that preceded changes in CI and SVR by 1-2 h. These data suggest that reduction in PRA may have contributed to the hemodynamic effects of this peak III PDE inhibitor.

Dihydropyridines↗

Severe bradycardia following electrical cardioversion for atrial tachyarrhythmias in patients with acute myocardial infarction.

Bradycardia following electrical cardioversion is an uncommon complication. The present report describes three patients who developed life-threatening bradycardia following electrical cardioversion for atrial tachyarrhythmias in the setting of an acute myocardial infarction. All three patients had multivessel coronary artery disease with a totally occluded right coronary artery and a possibility of ischemic sinus node dysfunction. When electrical cardioversion is undertaken for new onset of atrial tachyarrhythmia in the setting of an acute myocardial infarction, measures for immediate, temporary pacing should be easily available.

Aged↗

Early treatment with deferoxamine limits myocardial ischemic/reperfusion injury.

Oxygen-derived free radicals (the superoxide anion O2- and hydroxyl radical.OH) have been implicated in myocardial injury associated with coronary artery occlusion followed by reperfusion. Transition metals (such as iron or copper) are needed to catalyze the formation of the .OH radical and subsequent .OH-mediated lipid peroxidation, yet the role of these transition metals in the pathogenesis of myocyte necrosis remains undefined. To address this issue, 21 dogs underwent 2 h of coronary artery occlusion and 4 h of reperfusion. Each animal was randomly assigned into 1 of 3 treatment groups: 7 received the iron chelator deferoxamine beginning 30 min preocclusion, 7 received deferoxamine beginning 5 min prior to reperfusion, while 7 dogs served as saline controls. Deferoxamine effectively chelated free iron in both treatment groups (total urine iron content averaged 42 +/- 16, 662 +/- 177 and 803 +/- 2.5 micrograms in control, pretreated, and deferoxamine at reperfusion groups respectively; p less than 0.05), but had no significant effect on in vivo area at risk (AR), hemodynamic parameters, collateral blood flow during occlusion, or myocardial blood flow following reperfusion. Area of necrosis (AN) in dogs pretreated with deferoxamine (34.6 +/- 3.7% of the AR; p less than 0.05) was significantly smaller than that observed in the saline control group (55.4 +/- 4.7% of the AR). Deferoxamine administered at the time of reperfusion, however, had no significant effect on infarct size (AN/AR = 54.3 +/- 8.7%, p = NS vs. controls). Thus, early treatment with the iron chelator deferoxamine acutely reduced the extent of myocyte necrosis produced by 2 h of transient coronary artery occlusion in the canine model.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗