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Biomedical subjects

D Jain

Publications and source records attributed to D Jain.

At least 91 records · Page 5Linked to original sources

Quantitative 111In antimyosin antibody imaging to predict the age of myocardial infarction.

To establish whether quantitative 111In antimyosin uptake can be used to predict infarct age, we studied the heart-lung ratio in 107 images from 90 patients at various intervals following a Q-wave infarction. Imaging was performed 24 hours following 111In antimyosin injection. The HLR was measured as the ratio of the maximum counts in the infarcted myocardium to the adjacent lung background. The ratio ranged from 1.26 to 3.87, and declined with increasing infarct age. Infarcts were classified on the basis of age as type I (less than 3 days old), type II (less than 14 days), and type III (less than 90 days). True positive and false positive rates (TPR and FPR), and test-likelihood ratio calculations were performed for HLR thresholds ranging from 1 to 4, for the three infarct types. A FPR of 0% and likelihood ratio of infinity was obtained at a HLR threshold of 2.3 for type I infarcts (TPR 40.8%); at a HLR threshold of 2 for type II infarcts (TPR 50.6%), and a threshold of 1.8 for type III infarcts (TPR 52.6%). The likelihood of each infarct type can be estimated directly from the HLR for values below the above thresholds. These results show that quantitative 111In-antimyosin imaging may be used to predict infarct age.

Antibodies, Monoclonal↗

Assessment of right ventricular function. Role of nuclear imaging techniques.

Due to the complex geometry of the right ventricle, contrast angiography is not ideally suited for determining its volumes and for carrying out volume-based analyses. Nuclear cardiological techniques, being free from this limitation, have played an important role in understanding the right ventricular performance in various disease conditions. This technique is currently in clinical use and can be applied for assessing the role of right ventricular function in various cardiopulmonary diseases.

Heart↗

Purification and characterization of recombinant antistasin: a leech-derived inhibitor of coagulation factor Xa.

Antistasin (ATS) is a selective, tight-binding inhibitor of blood coagulation Factor Xa originally isolated from the salivary glands of the Mexican leech Haementeria officinalis. In order to provide sufficient quantities of ATS to further investigate the role of Factor Xa in blood coagulation, a recombinant version of ATS has been produced in an insect baculovirus host-vector system. In this study, we describe the purification and in vitro and in vivo characterization of a single recombinant antistasin (rATS) isoform. The purified protein constitutes a minor isoform relative to the more abundant ATS isoforms present in leech salivary gland extracts. In vitro, rATS inhibits purified human Factor Xa stoichiometrically, prolongs plasma-based clotting assays at nanomolar concentrations, and like native ATS, is cleaved at a single position by Factor Xa during the course of inhibition. An initial evaluation of the in vivo efficacy of rATS was addressed utilizing a rhesus monkey model of mild disseminated intravascular coagulation. rATS was shown to fully suppress thromboplastin-induced fibrinopeptide A generation in a dose-dependent fashion. The availability of rATS should provide a valuable tool for the critical evaluation of the specific role played by Factor Xa in coagulation.

Amino Acid Sequence↗

111In antimyosin antibody uptake is related to the age of myocardial infarction.

The intensity of 111In antimyosin uptake is related to the type (Q wave or non-Q wave), size, and location of an acute myocardial infarction. To determine whether the uptake intensity is also related to the infarct age, and to establish the time frame during which 111In antimyosin uptake occurs postinfarction, we studied a quantitative measure of uptake intensity, the heart-lung (HL) ratio, in 90 consecutive patients at various intervals following a Q wave infarction. Imaging was performed 24 hours following 111In antimyosin injection. Uptake of antimyosin could be demonstrated up to 154 days postinfarction. The HL ratio was measured as the ratio of the maximum counts in the infarcted myocardium to the adjacent lung background, and was 1.93 +/- 0.51 (mean +/- SD) overall. The ratio declined exponentially with increasing age of infarct. Using nonlinear regression analysis, 47% of the total variance of the HL ratio could be attributed to age alone (p less than 0.001). Sequential antimyosin imaging was performed in nine patients, with the first study between 4 and 15 days, the second between 50 to 100 days, and the third between 125 to 270 days after the onset of chest pain. The HL ratios were (mean +/- SD) 1.77 +/- 0.25 for scans between 4 and 15 days, 1.54 +/- 0.12 for scans between 50 and 100 days (p less than 0.02), and 1.42 +/- 0.16 (p less than 0.05) for scans between 125 to 270 days, further establishing the progressive reduction in 111In antimyosin uptake with age of myocardial infarction.

Adult↗

Effective thrombolysis without marked plasminemia after bolus intravenous administration of vampire bat salivary plasminogen activator in rabbits.

BACKGROUND: The use of recombinant tissue-type plasminogen activator (t-PA) in thrombolytic therapy is frequently associated with significant fibrinogenolysis. In contrast, recombinant vampire bat salivary plasminogen activator (Bat-PA) displays strict fibrin specificity, an attribute that could be desirable in a fibrinolytic agent. METHODS AND RESULTS: The efficacy and fibrin selectivity of Bat-PA was evaluated and compared with that of t-PA using a rabbit model of femoral arterial thrombosis. Administration of 8.1, 14, and 42 nmol Bat-PA/kg by bolus intravenous injection restored flow in 50%, 75%, and 80% of the rabbits, respectively. The incidence of reperfusion after bolus intravenous injection of 14 and 42 nmol t-PA/kg was 15% and 78%, respectively. The maximal femoral artery reperfusion flows were equivalent after treatment with 42 nmol Bat-PA/kg or 42 nmol t-PA/kg, but the time to reach maximal flow for Bat-PA was approximately one half that of t-PA. Furthermore, the rapid restoration of flow by 42 nmol Bat-PA/kg, in contrast to equimolar t-PA, was accomplished without fibrinogenolysis and with only small decreases in the plasminogen and alpha 2-antiplasmin levels. Equipotent doses of Bat-PA and t-PA both resulted in approximate 2.5-fold increases in the template bleeding times of aspirin-pretreated rabbits. The clearance of Bat-PA from rabbits exhibited biexponential elimination kinetics; approximately 80% was cleared by the relatively slow beta phase (half-life of 17.1 minutes). Overall, Bat-PA was cleared approximately fourfold slower than t-PA. CONCLUSIONS: Bolus intravenous administration of Bat-PA would facilitate prompt initiation of thrombolytic therapy, and the avoidance of plasminemia could result in fewer and less severe bleeding complications.

Animals↗

Immunoscintigraphy for detecting acute myocardial infarction without electrocardiographic changes.

OBJECTIVE: To establish whether immunoscintigraphy with antibody to myosin may detect acute myocardial infarction without electrocardiographic changes. DESIGN: Prospective study of patients with suspected acute myocardial infarction or unstable angina with cardiac imaging with 111indium myosin antibody, estimation of cardiac enzyme concentrations, electrocardiography, 201thallium imaging, and radionuclide ventriculography. SETTING: Coronary care unit in a district general hospital. PATIENTS: 119 Consecutive patients with suspected acute myocardial infarction or unstable angina. Patients with cardiomyopathy, myocarditis, valvular heart disease, myocardial infarction or cardiac surgery in the previous two weeks or with left bundle branch block and women of childbearing age were excluded. RESULTS: Of 75 patients with suspected acute myocardial infarction, seven had no diagnostic electrocardiographic changes despite normal conduction patterns. Immunoscintigraphy with myosin antibody disclosed necrosis in all seven patients, which was localised in regions supplied by diseased coronary arteries in all but one. Six patients had abnormal images on 201thallium imaging, and all seven had abnormal wall motion at the site of antibody uptake. One patient with minimal left main stem and right coronary artery atheroma had uptake of antibody at two discrete sites. CONCLUSIONS: Immunoscintigraphy with antibody to myosin confirms myocardial infarction in the absence of electrocardiographic changes and discloses the site of infarction.

Adult↗

Clinical and prognostic significance of lung thallium uptake on rest imaging in acute myocardial infarction.

Exercise-induced pulmonary uptake of thallium-201 in patients with ischemic heart disease is probably due to transient pulmonary edema and left ventricular failure induced by exercise. The significance of increased lung uptake of thallium-201 at rest after acute myocardial infarction (AMI) has not been described. Ninety-six patients admitted with chest pain for suspected AMI or unstable angina underwent thallium-201 imaging at rest. Using conventional diagnostic criteria, 62 had AMI, 12 had unstable angina and 22 had neither. Increased lung uptake of thallium-201 was present in 24 of the total 96 (25%) patients, 20 of the 62 (32%) patients with AMI and 4 of 34 (13%) patients with no evidence of infarction. In the AMI group, those with increased lung thallium-201 uptake had a higher mean +/- standard deviation segmental thallium-201 defect score (22 +/- 7 vs 12 +/- 8, p less than 0.0001), lower ejection fraction (35 +/- 14 vs 49 +/- 14%, p less than 0.002), higher peak creatine kinase levels (2,410 +/- 1,247 vs 1,496 +/- 1,228 IU/liter, p less than 0.01), higher wall motion abnormality score (25 +/- 13 vs 13 +/- 12, p less than 0.0001), increased incidence of clinical in-hospital heart failure (15 of 20 vs 7 of 42, p less than 0.0001) and higher short-term mortality (4 of 20 vs 1 of 42, p less than 0.02) compared to those without increased lung thallium-201 uptake.(ABSTRACT TRUNCATED AT 250 WORDS)

Angina, Unstable↗

Ranolazine (RS-43285): a preliminary study of a new anti-anginal agent with selective effect on ischaemic myocardium.

Ranolazine (RS-43285) has been shown to possess significant anti-ischaemic properties in a canine model of reversible myocardial ischaemia. The clinical efficacy of this new agent was assessed by a single blind, placebo controlled study of 14 patients with chronic stable angina. A 2 week placebo phase was followed by therapy with 30 mg and 60 mg of ranolazine tid for 2 weeks each. Graded, symptom limited treadmill exercise tests were performed at the end of each phase, 1.5 h (AM) and 7 h (PM) after the morning dose. An additional exercise test 1.5 h after the first dose of 30 mg was included to assess the acute dose response. In the AM study, the mean exercise time increased from 6.9 min (placebo) to 7.8 min after the first dose of 30 mg and to 8.2 min and 8.5 min respectively at the end of 30 mg and 60 mg phases. In the PM study, exercise time improved from 6.5 min (placebo) to 8.2 min and 7.8 min respectively at the end of 30 mg and 60 mg phases. The time to onset of angina showed a similar improvement. No significant changes were observed in the resting and peak exercise heart rates and blood pressure. This preliminary study suggests that ranolazine may significantly prolong exercise time in patients with stable coronary artery disease without altering heart rates and blood pressure.

Acetanilides↗

Haemostatic abnormalities in brain tumours.

The coagulation profile of 25 patients with brain tumours was studied preoperatively, intraoperatively and postoperatively. Ten patients had abnormal coagulation status preoperatively. Surgical intervention led to either an alteration of preexisting abnormality or appearance of new coagulation abnormality. Disseminated intravascular coagulation and fibrinolysis occurred with equal frequency in patients with meningiomas and gliomas. The alterations as a result of surgery were transient and compensated rapidly.

Adult↗

111In-antimyosin antibody imaging for detection of myocardial infarction: a quantitative approach.

Indium-111-antimyosin imaging has been shown to be a sensitive and specific method for detecting myocardial necrosis, but a quantitative method for interpretation of 111In-antimyosin planar images is lacking. A prospective study was performed in 114 patients with suspected acute myocardial infarction using planar 111In-antimyosin imaging. A ratio of maximum myocardial uptake counts (H) (9 X 9 pixels) over adjacent lung background (L), i.e. H/L ratio, was obtained from 24 and 48 h images. This value was compared with peak creatine kinase (CK) enzyme and left ventricular ejection fraction (LVEF). The patients were classified into groups based upon standard criteria for Q-wave acute myocardial infarction (Q-MI) (n = 50), non-Q-MI (n = 21), unstable angina (n = 15) and those with no evidence of MI or ischaemia (n = 28). The mean +/- S.D. H/L ratio in the Q-MI group was 2.28 +/- 0.50 (24 h, left anterior oblique, LAO, view) and was greater than the non-Q-MI group (1.98 +2- 0.30) (P less than 0.02). In patients with unstable angina (UA), seven had a high ratio (1.75 +/- 0.29) and eight had a lower ratio (1.29 +/- 0.07). In the group of patients without MI or UA, the ratio was 1.24 +/- 0.11 and this was significantly lower than the Q-MI and non-Q-MI groups and those patients with UA and positive 111In uptake (P less than 0.001, respectively). However, there was no significant difference between old MI and patients without evidence of MI or UA.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Indium-111-antimyosin images compared with triphenyl tetrazolium chloride staining in a patient six days after myocardial infarction.

The results of indium-111 (111In) antimyosin imaging during life and the findings on postmortem imaging and triphenyl tetrazolium chloride (TTC) staining of the heart are reported from a patient who received 111In-antimyosin on the sixth day following myocardial infarction and died after imaging the next day. The planar images obtained during life showed abnormal 111In-antimyosin uptake in the posterior, lateral, and apical walls of the left ventricle. Autopsy revealed extensive infarction of the left ventricular lateral and posterior walls with cardiac rupture, which was the cause of sudden death. Direct imaging of the sliced specimen of heart revealed abnormal tracer uptake in the lateral and posterior walls of the left ventricle, which correlated closely with the area of necrosis outlined by TTC staining. Our results confirm the experimental findings that antimyosin antibody binds specifically to the acute irreversibly damaged myocardial cells. A high degree of tracer uptake can be seen even when 111In-antimyosin is injected six days postinfarction.

Aged↗

Lack of effect of asymmetrical dosage timing of isosorbide-5-mononitrate on nitrate tolerance during long-term administration.

Isosorbide 5-mononitrate is an active metabolite of isosorbide dinitrate and possesses many theoretical advantages over its parent drug. However, the development of partial tolerance has been demonstrated when the drug is given 12 hourly or 8 hourly. We have therefore evaluated the acute and sustained (2 weeks) effects of isosorbide-5-mononitrate 40 mg given twice daily (08.00 h and 14.00 h, allowing an 18-h dose-free period) in 19 patients with stable chronic angina, using computerized exercise testing and a placebo-controlled, double-blind, randomized trial protocol. There were two phases of 2 weeks each in which patients received placebo or active isosorbide-5-mononitrate. Acute testing was performed 2 h after the first dose and chronic testing 2 h after the morning dose on Day 14. Acute testing showed an increase in exercise time from a mean (SD) of 6.7 (2.2) min to 10.1 (2.95) min (P less than 0.01) after a single dose of isosorbide-5-mononitrate 40 mg. The time to 1 mm of ST depression, and rest and peak exercise heart rates increased significantly during acute testing with isosorbide-5-mononitrate; resting and peak exercise systolic blood pressures fell significantly. Due to drop outs cross-over analysis was performed on 11 patients who completed both chronic phases and 13 patients were assessed for the comparison of acute isosorbide-5-mononitrate with chronic isosorbide-5-mononitrate. After 2 weeks of therapy exercise time did not show a sustained increase 8.01 (2.14) min chronic placebo to 8.58 (1.93) min chronic isosorbide-5-mononitrate.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Effects of carvedilol in patients with impaired left ventricular function due to ischaemic heart disease.

In this single-blind, placebo-controlled trial, carvedilol, a nonselective beta-blocking and vasodilating agent was studied in six patients with chronic stable angina. All patients had reproducible treadmill exercise time without medical treatment and developed chest pain in association with ST-segment depression (greater than 1 mm at J + 80 msec) on exercise. None had a history of rest or unstable angina or myocardial infarction within three months prior to the study. In all patients, anti-anginal medication except sublingual nitroglycerin was discontinued for 10 days. The patients entered an initial two week-phase of placebo. They then received carvedilol, 25 mg and then 50 mg twice daily for two weeks on each dose, followed by another two week-placebo-phase. Radionuclide ventriculography was performed at the end of each phase at rest and during maximal symptom-limited exercise. Bicycle ergometry was carried out in the supine position with incremental workloads. Exercise time and workload were recorded at the end of the first phase and imaging was performed at the same time and workload throughout the trial. Carvedilol produced a dose-related reduction in rest and exercise heart rate and blood pressure. Peak exercise ST-segment change was reduced by both doses of carvedilol, but this did not achieve a level of significance. After the first placebo phase all patients had abnormal left ventricular wall motion and resting ejection fraction (range: 35% to 45%). Four out of six patients had significant improvement in wall motion abnormalities, in two patients there was no change, and none developed a deterioration in abnormal wall motion.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗