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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
PubMed1995

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↗
PubMed1994

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1990

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↗
PubMed1990

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↗
PubMed1989

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↗
PubMed1989

Evaluation of Fourier transform filter for high-resolution ECG.

The high-resolution electrocardiography has become an important clinical tool for analyzing the high-frequency content of electrocardiograms (ECGs). Recent emphasis has been on the detection of ventricular late potential activity due to its ability to predict ventricular tachycardia (VT) in myocardial infarction (MI) patients. To accentuate the high-frequency components, the signal-averaged ECG data are filtered using high-pass filters. Two types of filters used in commercial systems, bidirectional Butterworth and Fourier transform filters, are compared using a common signal-averaged ECG data base. Signal-averaged ECG data acquired at two clinical sites (Mayo Clinic and Bowman Gray School of Medicine) using the MAC15 HIRES system were filtered using a 40-Hz fast Fourier transform (FFT) filter with a 6 dB/octave rolloff on an IBM-compatible personal computer. The same average data were filtered using a 40-Hz bidirectional Butterworth filter with similar rolloff. Using a common algorithm, outputs of both filters were used to compute vector magnitude and to obtain the measurements to quantify high-frequency, low-amplitude (HFLA) signals. The measurements include total QRS duration, duration of HFLA signals, root mean square voltage, and mean voltage in the terminal 40 msec. Applying the published criteria for late potentials, sensitivity and specificity were computed for both filters on data obtained from 59 patients of old MI (group 1, 29 with clinical or inducible VT and group 2, 30 with no history of VT and noninducible). The results were very similar, and both filters were found to be functionally equivalent.

Action Potentials↗
PubMed1989

Favourable long term prognosis in patients with non-Q wave acute myocardial infarction not associated with specific electrocardiographic changes. Diltiazem Reinfarction Study Research Group.

Electrocardiograms obtained serially from 544 patients with non-Q wave infarction in the Diltiazem Reinfarction Study were analysed to compare the short term (less than or equal to 14 days) and long term (one year) follow up of 105 patients (19%) whose admission electrocardiogram showed no localisable repolarisation abnormalities (group 1) with the outcome in 439 patients (81%) who had ST-T wave abnormalities (group 2) localised to two or more contiguous leads within an anterior, inferior, or lateral lead group. There were no major between group differences in baseline clinical variables, concomitant medications, or treatment allocation (diltiazem v placebo). Group 2 patients, in the first year, had a higher incidence of early recurrent ischaemia (angina greater than or equal to 24 hours after myocardial infarction associated with ischaemic repolarisation changes), reinfarction, and readmission for chest pain than group 1 patients, despite comparable creatine kinase and creatine kinase MB activities in both groups. About 20% of patients with acute non-Q wave myocardial infarction did not have definable ST-T wave abnormalities. These patients had a similar clinical and enzymatic profile as patients with non-Q wave infarction with definable ST-T wave abnormalities and they were more likely to have a favourable short term and long term outcome.

Creatine Kinase↗
PubMed1988

High-resolution ECG on a standard ECG cart.

High-resolution (HI-RES) ECG analysis software and a new front end have been designed for a standard 12-lead ECG cart, MAC-12. The front end acquires orthogonal ECG at 1,000 samples/sec and 1.2 microV/bit and transmits to the cart. The HI-RES software delineates QRS complexes and correlates them with a template in frequency domain to compute an average cardiac complex (P, QRS, and T). This complex is used for analysis of late potentials, bundle of His activity, and detection of coronary artery disease using its high-frequency content. Both time- and frequency-domain methods are implemented for analysis of ventricular late potentials. In the time-domain method, the average beat is bandpass filtered using three lower cutoff frequencies--25, 40, and 80 Hz--with the higher cutoff at 250 Hz. For each of these frequencies, the following features are extracted: RMS voltages in terminal 40 and 50 msec; ventricular activation time; and duration of high-frequency, low-amplitude signals. The frequency-domain analysis examines the spectral contents of the windowed segment of terminal QRS; ST-segment; and a combined segment of QRS and ST. The spectral features include ratios of magnitudes of Fourier coefficients and areas above 20 Hz, dB drop at 40 Hz, and areas after 60 dB offset. Initial testing of this system is complete, and it is due for clinical trials soon.

Bundle of His↗
PubMed1987

An experimental microcomputer controlled system for synchronized pulsating anti-gravity suit.

An experimental system to deliver synchronized external pressure pulsations to the lower body is described in this technical note. The system is designed using a microcomputer with a real time interface and an electro-pneumatic subsystem capable of delivering pressure pulses to a modified anti-G suit at a fast rate. It is versatile, containing many options for synchronizing, phasing and sequencing of the pressure pulsations and controlling the pressure level in the suit bladders. Details of its software and hardware are described along with the results of initial testing in a Dynamic Flight Simulator on human volunteers.

Computers↗
PubMed1986

17 alpha-allyl estradiol analogues as candidates for development of high-affinity fluorescein-estradiol conjugates.

In order to develop stable, high-affinity fluorescein-estradiol conjugates, the fluorescein moiety must be leashed to the estradiol molecule at a point which interferes least with estradiol's binding to the receptor. Because of the high affinity of 17 alpha-substituted estradiol (e.g. ethynyl estradiol), we investigated a series of 17 alpha-substituted estradiol compounds to determine the optimal properties of a leash at this position. Twelve estradiol derivatives bearing a three-carbon 17 alpha side chain with or without a terminal functional group and with varying degrees of unsaturation were synthesized. Initial comparison of the receptor binding affinities of some of these derivatives suggested that three factors might reduce affinity: internal hydrogen bonding of the 17 beta-hydroxyl proton with an oxygen atom of the 17 alpha side chain; hydrophilicity of the ligand; or steric interference of the side chain with receptor binding. Further comparisons were designed to evaluate the relative contribution of these factors. The results suggest that the relative affinities of these 17 alpha-substituted estradiol derivatives are influenced primarily by the steric interference of the side chains and also by their hydrophilicity. Internal hydrogen bonding involving the 17 beta-hydroxyl proton does not seem to have a profound effect.

Animals↗
PubMed1982

A simple VCG system with temporal dimension, directional reference and display of component loops.

A vectorcardiogram (VCG) represents the cardiac electrical activity as continuous vector loops in three mutually perpendicular planes, namely frontal, transverse and sagittal. This technical note describes a simple system developed to record VCG with an ordinary x-y oscilloscope and simple camera. Facilities exist for recording VCG with temporal dimension, directional reference and display of specific component loops of a cardiac cycle. The system is in use for recording VCG at rest and during stress tests involving exercise and hypoxia at simulated altitude. Its performance has been found satisfactory and the system highly reliable.

Data Display↗