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Biomedical subjects

J T Watson

Publications and source records attributed to J T Watson.

At least 109 records · Page 6Linked to original sources

Implantable ventricular assist systems.

A major goal of the Circulatory Support Program of the National Heart, Lung, and Blood Institute (NHLBI) is the development of a tether-free implantable ventricular assist system (VAS) to rehabilitate patients with advanced heart disease. In 1980, the NHLBI initiated a targeted program to develop and integrate implantable electromechanically powered VASs capable of operating for at least 2 years. The objectives of the program are to complete the development of the VAS and perform in vitro and in vivo evaluation studies. This article summarizes the research status of this NHLBI-sponsored program. It defines the VAS system requirements, describes the systems under development, identifies progress achieved to date, and identifies research challenges.

Animals↗

Electron capture negative chemical ionization mass spectrometry of chemically oxidized corticosteroids.

A procedure which can be used to increase the electron affinity of corticosteroids for purposes of quantitative analysis is proposed. Ten important corticosteroids are chemically oxidized to 1,4-androstadien-3,11,17-trione or 4-androsten-3,6,17-trione structural steroid analogs to enhance their electrophilicity prior to detection by electron capture negative chemical ionization mass spectrometry. The choice of oxidation reagent, a preliminary assessment of the structure-response relationship of the oxidation products, the optimization of negative ion formation as a function of source temperature and the basis for distinguishing the isomers dexamethasone and betamethasone are addressed.

Adrenal Cortex Hormones↗

Mechanical support for the failing heart.

The National Heart, Lung, and Blood Institute (NHLBI) has sponsored considerable research directed toward basic studies on the etiology of heart disease and atherosclerosis. While progress has been very encouraging there are still significant numbers of patients with end-stage heart disease. NHLBI initiated goal-oriented research activities on the artificial heart based upon the recommendation of the National Heart Advisory Council in 1964. The major goal of the Artificial Heart Program was to develop devices which could be effectively used to rehabilitate patients with end-stage heart disease. This paper will describe the evolution and specific program goals of the Artificial Heart Program and provide a description of the left ventricular assist system (LVAS) and total artificial heart (TAH) research efforts. Specific attention will be directed toward defining device requirements, descriptions of the blood pump and energy converter, control system operation and energy transmission methods. A summary of experimental results and current development status will also be provided.

Assisted Circulation↗

Clinical temporary ventricular assist. Pathologic findings and their implications in a multi-institutional study of 41 patients.

Forty-one patients, distributed among four centers, had left (33 patients), right (five), or bilateral (three) temporary ventricular assistance with textured (24) or smooth (17) surfaced diaphragm pumps, during an evaluation supported by the National Institutes of Health. Cardiac failure had occurred in 39 postoperative patients (after aorta-coronary bypass [23], valve replacement [four], both [nine], or other [three]), with total cardiopulmonary bypass time mean 306 minutes (range 69 to 600). Two patients had cardiomyopathy. Death of 35 nonsurvivors was due to myocardial necrosis (14), hemorrhage (nine), cerebrovascular accidents (three), infection (three), and other (six). Mean duration of support in all patients was 62 hours. In 16 patients (40%) whose condition improved, cardiac assist duration was mean 127 hours (range 48 to 264), compared with mean 19 hours (range 1 to 120) in 25 who did not. Of 17 patients in whom duration of support exceeded 72 hours, 15 (88%) improved, 11 were weaned, and six survived long term. Tissue examination (in 33 patients) by biopsy at pump implantation or autopsy revealed coagulation or contraction band myocyte necrosis, with or without hemorrhage, in 26 patients; of these, 10 improved and six were long-term survivors. Pump-related complications (two) included pulmonary embolism, most likely related to a cannulation site thrombus, and an aortic cannulation site infection in one patient each. This study suggests that mechanical cardiac assist may be accomplished with a low complication rate; should not necessarily be denied to patients with existing necrosis, because myocardial necrosis does not preclude improvement or survival; and frequently leads to functional myocardial recovery if patients survive early noncardiac complications, often the result of long duration of cardiopulmonary bypass.

Adolescent↗

Quantitative methodology for corticosteroids based on chemical oxidation to electrophilic products for electron capture-negative chemical ionization using capillary gas chromatography-mass spectrometry. I. Assessment of feasibility in the analysis of horse urine for dexamethasone.

Sensitive and specific methodology based on capillary column gas chromatography-electron capture-negative chemical ionization-mass spectrometry has been developed for the quantitative analysis of corticosteroids from biological fluids. The feasibility of this method is demonstrated in the quantitative analysis of dexamethasone in horse urine following administration of the drug. A structurally similar compound, 6 alpha-methylprednisolone, is added to the urine as an internal standard. The free dexamethasone and the internal standard are extracted and oxidized to high-electron-affinity 1,4-androstadiene-3,11,17-trione structural analogs and then analyzed by capillary column gas chromatography-electron capture-negative chemical ionization-mass spectrometry.

Adrenal Cortex Hormones↗

The present and future of cardiac assist devices.

This article describes the status of development of an implantable electrically powered ventricular assist device designed for a minimum of a 2-year operation in patients with advanced heart failure. While these devices are envisioned for chronic support of the failing circulation, air-driven blood pumps have been used to provide life support to patients with acute ventricular dysfunction produced by a reversible myocardial injury of unknown origin. The physical and hemodynamic characteristics of the mechanical circulatory support devices are detailed. Clinical indications and results are provided on patients treated with temporary ventricular assist devices. Long-term follow-up of some patients has demonstrated sustained improved cardiac function for up to 5 years after treatment. Reperfusion injury and postischemic myocardial depression are discussed as two possible etiologies of acute ventricular dysfunction. In the summer of 1984, investigators began a collaborative program to test the engineering reliability of implantable devices as well as their performance in animals. This 3-year Device Readiness Program had a goal of demonstrating an 80% reliability with a confidence interval of 70%. In the future, the implantable device will be evaluated clinically in selected patients to investigate its ability to support circulatory functions and the results of host-device interactions. These devices have potential both as experimental tools in studies of heart and vascular disease and in the treatment of patients with intractable heart failure.

Adult↗

Long-term follow-up of postcardiotomy patients with profound cardiogenic shock treated with ventricular assist devices.

Success of ventricular assist devices in patients with postcardiotomy shock has provided enough survivors to allow evaluation of the length and quality of life. Fifteen survivors from 28 to 68 years (mean 53) old from four centers were followed for 6 to 77 months (mean 35) after discharge from the hospital. Four patients suffered perioperative myocardial infarctions. In three patients, ventricular function was normal before surgery and remained so afterward. Of 12 patients with moderate or severely impaired ventricular function, five improved, five were unchanged, and two were worse. One patient died 6 months after surgery of cardiomyopathy. Seven patients are employed full-time and one works part-time. Five patients are retired but active and one is moderately disabled. NYHA functional class improved in the patients as a group: 13 were in classes III and IV before surgery and 13 were in classes I and II after surgery. Two patients had noncardiac partial disability. Survivors of ventricular assist device support for postcardiotomy shock have an excellent chance for high-quality life and the risk of crippling cardiac disability is small.

Adult↗

Application of fast atom bombardment mass spectrometry to biological samples: analysis of urinary metabolites of acetaminophen.

Fast atom bombardment (FAB) is useful for the characterization of all major metabolites of the analgesic acetaminophen (APAP). It is particularly useful for providing mass spectra of the polar glucuronide and sulfate conjugates which eluded identification by field desorption and other more conventional methods of ionization. A protocol is described for the use of FAB in the identification of urinary APAP metabolites isolated by reversed phase high-performance liquid chromatography (HPLC) following therapeutic dosages of the drug. A tentative set of recommendations for the off-line use of HPLC and FAB is directed towards solving problems encountered when using these two analytical techniques in concert. In addition, a method for calculating the signal to background ratio (S/B) for analyte peaks in FAB spectra from selected relative ion intensities is proposed. Examples are presented that show the potential of S/B as an empirical parameter for judging the quality of FAB spectra.

Acetaminophen↗

Iodination of docosahexaenoic acid by lactoperoxidase and thyroid gland in vitro: formation of an lodolactone.

In the presence of iodide, hydrogen peroxide and lactoperoxidase, docosahexaenoic acid (22:6 omega 3) was converted into iodinated compounds. The major product was identified as 5-iodo-4-hydroxy-7, 10, 13, 16, 19-docosapentaenoic acid, gamma-lactone, on the basis of 125 I incorporation, mass spectrometry, chemical modifications and proton nuclear magnetic resonance spectroscopy. Iodolactonization of docosahexaenoic acid occurred in the rat thyroid in vitro and was inhibited by the peroxidase inhibit or methimazole. These data indicate that formation of an idolactone constitutes one pathway of docosahexaenoic acid metabolism which could be expressed in tissues containing an iodide peroxidase.

Animals↗

Intraaortic balloon counterpulsation: its influence alone and combined with various pharmacological agents on regional myocardial blood flow during experimental acute coronary occlusion.

We investigated the separate and combined effects of pharmacological and intraaortic balloon pump (IABP) support on regional myocardial blood flow in an experimental model of acute myocardial ischemia. Chloralose-anesthetized dogs were ventilated with an oxygen-air mixture, and cardiac output, arterial pressure, and heart rate were held constant. Treatment was begun 20 minutes following permanent ligation of the left anterior descending coronary artery (LAD). We evaluated the following pharmacological interventions: 25% hypertonic mannitol, isosorbide dinitrate, methyl-prednisolone sodium succinate, and propranolol. We measured left ventricular hemodynamics and intramyocardial blood flow by the radioactive microsphere technique prior to treatment and at 15-minute intervals thereafter. Compared with control measurements 20 minutes following LAD ligation, collateral blood flow to ischemic myocardium tended to decrease with no treatment. Treatments with the four pharmacological interventions and with IABP alone produced no significant improvement in collateral blood flow to ischemic myocardium 15 minutes following treatment. In contrast, mannitol, isosorbide dinitrate, and propranolol, each combined with IABP support, produced significant improvements in collateral flow within the same time periods. In nonischemic myocardium, combined pharmacological and IABP treatment did not enhance myocardial blood flow above that obtained with the pharmacological agents alone. The most effective combination of mechanisms for improving the ischemic region's myocardial blood flow appeared to be a reduction of extravascular coronary flow resistance coupled with a simultaneous increase in diastolic arterial pressure.

Animals↗

Metabolism of linoleic and arachidonic acids in VX2 carcinoma tissue: identification of monohydroxy octadecadienoic acids and monohydroxy eicosatetraenoic acids.

The metabolism of arachidonic and linoleic acids by VX2 carcinoma tissue in vitro was determined. Prostaglandin E2 was the major metabolic product of arachidonic acid in the neoplastic tissue. Minor products accounting for 3- 8% of arachidonic acid metabolism were II-hydroxy-5, 8, 12, 14-eicosatetraenoic acid (II-HETE) and 15-hydroxy-5, 8, 11, 13-eicosatetraenoic acid (15-HETE). Linoleic acid was converted to a mixture of 9-hydroxy-10, 12-octadecadienoic acid (9-HODD) and 13-hydroxy-9, 11-octadecadienoic acid (13-HODD). The conversion of linoleic acid to monohydroxy C-18 fatty acids varied from 40-80% 9-HODD and 20-60% 13-HODD in tumor tissue harvested from different animals. The quantity of monohydroxy C-18 fatty acids biosynthesized by VX2 carcinoma tissue from endogenous linoleic acid equals or exceeds that of prostaglandin E2 biosynthesis from endogenous arachidonic acid. The presence of a hydroxyl group adjacent to a conjugated diene suggest that the monohydroxy C-18 and monohydroxy C-20 fatty acids were formed via the action of lipoxygenase-like enzymes. These lipoxygenase-like reactions are inhibited by indomethacin in a concentration-dependent fashion similar to the inhibition of prostaglandin E2 biosynthesis. The enzymes catalyzing the lipoxygenase-like reactions of linoleic and arachidonic acids are localized in the microsomal fraction of VX2 carcinoma tissue. These data suggest that the lipoxygenase-like reactions are catalyzed by fatty acid cyclooxygenase and that there are two major pathways of fatty acid cyclooxygenase metabolism of polyenoic fatty acids in the neoplastic tissue. One pathway involves the formation of prostaglandin E2 via cyclic endoperoxy intermediates. The second pathway involves the formation of monohydroxy C-18 fatty acids from linoleic acid via lipoxygenase-like reactions.

Animals↗