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Biomedical subjects

D W Miller

Publications and source records attributed to D W Miller.

At least 181 records · Page 10Linked to original sources
PubMed1984

Synthesis, spectral analysis, and mutagenicity of 1-, 3-, and 6-nitrobenzo[a]pyrene.

The mutagenic environmental pollutants 1-, 3-, and 6-nitrobenzo[a]pyrene were synthesized. Nitration of 7,8,9,10-tetrahydrobenzo[a]pyrene with sodium nitrate in trifluoroacetic acid and acetic anhydride at ambient temperature gave a mixture of 1-, 3-, and 6-nitro-7,8,9,10-tetrahydrobenzo[a]pyrene, which was separated by chromatography. Dehydrogenation of the isolated nitrotetrahydrobenzo[a]pyrenes with 2,3-dichloro-4,5-dicyano-1,6-benzoquinone produced 1-, 3-, and 6-nitrobenzo[a]pyrene in high yield. Comparison of the spectral data of these compounds with those obtained from direct nitration of benzo[a]pyrene confirmed that 1- and 3-nitrobenzo[a]pyrenes are indeed the minor products of the latter reaction. This confirmation also verifies that 1- and 3-nitrobenzo[a]pyrene were the minor nitrated products of benzo[a]pyrene formed in model air atmospheres. The 1-, 3-, and 6-nitrobenzo[a]pyrene were mutagenic in Salmonella typhimurium tester strains TA98 and TA100 in the presence of a mammalian microsomal (S9) activating system. Both 1- and 3-nitrobenzo[a]pyrene, but not 6-nitrobenzo[a]pyrene, were also direct-acting mutagens in these strains. However, only 6-nitrobenzo[a]pyrene exhibited weak mutagenic activity when tested in Chinese hamster ovary cells, while only 3-nitrobenzo[a]pyrene produced a concentration-dependent decrease in cellular survival.

Benzopyrenes↗
PubMed1984

Transformation of 1- and 2-methylnaphthalene by Cunninghamella elegans.

Cunninghamella elegans metabolized 1- and 2-methylnaphthalene primarily at the methyl group to form 1- and 2-hydroxymethylnaphthalene, respectively. Other compounds isolated and identified were 1- and 2-naphthoic acids, 5-hydroxy-1-naphthoic acid, 5-hydroxy-2-naphthoic acid, 6-hydroxy-2-naphthoic acid, and phenolic derivatives of 1- and 2-methylnaphthalene. The metabolites were isolated by thin-layer and reverse-phase high-pressure liquid chromatography and characterized by the application of UV-visible absorption, 1H nuclear magnetic resonance, and mass spectral techniques. Experiments with [8-14C]2-methylnaphthalene indicated that over a 72-h period, 9.8% of 2-methylnaphthalene was oxidized to metabolic products. The ratio of organic-soluble in water-soluble metabolites at 2 h was 92:8, and at 72 h it was 41:59. Enzymatic treatment of the 48-h aqueous phase with either beta-glucuronidase or arylsulfatase released 60% of the metabolites of 2-methylnaphthalene that were extractable with ethyl acetate. In both cases, the major conjugates released were 5-hydroxy-2-naphthoic acid and 6-hydroxy-2-naphthoic acid. The ratio of the water-soluble glucuronide conjugates to sulfate conjugates was 1:1. Incubation of C. elegans with 2-methylnaphthalene under an 18O2 atmosphere and subsequent mass spectral analysis of 2-hydroxymethylnaphthalene indicated that hydroxylation of the methyl group is catalyzed by a monooxygenase.

Kinetics↗
PubMed1984

Effects of a fluoro substituent on the fungal metabolism of 1-fluoronaphthalene.

The metabolism of 1-fluoronaphthalene by Cunninghamella elegans ATCC 36112 was studied. The metabolites were isolated by reverse-phase high-pressure liquid chromatography and characterized by the application of UV absorption, 1H nuclear magnetic resonance, and mass spectral techniques. C. elegans oxidized 1-fluoronaphthalene predominantly at the 3,4- and 5,6-positions to form trans-3,4-dihydroxy-3,4-dihydro-1-fluoronaphthalene and trans-5,6-dihydroxy-5,6-dihydro-1-fluoronaphthalene. In addition, 1-fluoro-8-hydroxy-5-tetralone, 5-hydroxy-1-fluoronaphthalene, and 4-hydroxy-1-fluoronaphthalene as well as glucoside, sulfate, and glucuronic acid conjugates of these phenols were formed. Circular dichroism spectra of the trans-3,4- and trans-5,6-dihydrodiols formed from 1-fluoronaphthalene indicated that the major enantiomers of the dihydrodiols have S,S absolute stereochemistries. In contrast, the trans-5,6-dihydrodiol formed from 1-fluoronaphthalene from 3-methylcholanthrene-treated rats had Cotton effects that are opposite in sign (R,R) to those formed by C. elegans. The results indicate that the fungal monooxygenase-epoxide hydrolase systems are highly stereoselective in the metabolism of 1-fluoronaphthalene and that a fluoro substituent blocks epoxidation at the fluoro-substituted double bond, decreases oxidation at the aromatic double bond that is peri to the fluoro substituent, and enhances metabolism at the 3,4- and 5,6-positions of 1-fluoronaphthalene.

Animals↗
PubMed1983

Synthesis and characterization of the anomeric pair of 17 beta-glucuronides of ethynylestradiol.

The alpha- and beta-anomers of the 17 beta-D-glucuronide conjugate of ethynylestradiol were synthesized by the SnCl4-promoted reaction between beta-acetoxy GAM and the t-17 beta-hydroxyl group of EE2-3-acetate. The conjugates were resolved by crystallization and HPLC. Positive identification was established by u.v. spectrophotometry, i.r. and mass spectrometry and 1H- and 13C-n.m.r. The structure of the beta-anomer was confirmed by X-ray crystallographic analysis. In addition, the alpha-anomer was refractory to hydrolysis by bovine beta-glucuronidase, establishing a biochemical difference between the conjugate pair.

Chromatography, High Pressure Liquid↗
PubMed1983

Influence of propranolol on supraventricular tachycardia early after coronary artery revascularization. A randomized trial.

A total of 116 patients undergoing coronary revascularization were randomized preoperatively in a double-blind manner to receive 80 mg daily of propranolol or placebo in the postoperative period. Preoperatively, all patients had been receiving at least 80 mg of propranolol a day to the time of the operation. In addition, all patients had a left ventricular ejection fraction of 0.4 or more, no history of supraventricular tachyarrhythmia (SVT), and no need of digitalis preparations or other antiarrhythmic drugs. All patients were monitored for 5 days and propranolol or placebo was started 24 hours postoperatively. SVT was documented with biatrial electrograms in all cases. Study groups were similar in postoperative creatine kinase MB levels and postoperative weight gain, but the placebo group tended to be older and have more grafts per patient. Seven patients randomized were dropped from the study, two with perioperative infarction, four with persistent ventricular arrhythmias necessitating quinidine or procainamide, and one with persistent postoperative hypotension (placebo). There were no significant differences in the incidence of postoperative SVT in these two groups: 13.2% in the propranolol group and 16.1% in the placebo group. We conclude that 80 mg daily of propranolol given postoperatively to patients undergoing coronary revascularization does not effectively reduce the incidence of SVT.

Clinical Trials as Topic↗
PubMed1982

Dacron patch closure of aortic annulus mycotic aneurysms.

Six patients with large mycotic aortic annular aneurysms were successfully operated on over a 3-year period. Aortic valve replacement was facilitated in all six patients by closing the orifice of the abscess with a Dacron patch and then seating the prosthetic valve at the level of the aortic annulus. In each case, a portion of the prosthetic valve ring was sutured directly to the patch. No patient has clinical evidence of a perivalvular leak 18-48 months after operation. One patient required reoperation to close a ventricular septal defect caused by partial patch dehiscence. Dacron patch closure has been highly effective in our experience and is simpler than many other options.

Adult↗
PubMed1982

Results of a survey of the professional activities of 811 cardiopulmonary perfusionists.

We queried 811 cardiopulmonary perfusionists in North America on the equipment and techniques they currently use for cardiopulmonary bypass, their professional training, and their income structure. Most cardiac surgical teams use one of four types of bubble oxygenators; only 5% use a membrane oxygenator exclusively. More than 80% monitor the activated clotting time during cardiopulmonary bypass, and 61% confirm the adequacy of heparinization with this test before initiating bypass. Most perfusionists surveyed, 507, are hospital salaried; 117 are employed by cardiac surgeons; and 72 have established a fee for service arrangement. In 1980, reported incomes for cardiopulmonary perfusionists ranged between $12,000 and $110,000, with a mean of $25,000. Only 196 respondents (24%) were graduates of accredited training programs in perfusion technology, but 618 (76%) were board certified in cardiovascular perfusion. This study presents an in-depth survey of the present status of perfusion technology, a discipline which has grown up around the practice of cardiac surgery.

Cardiopulmonary Bypass↗
PubMed1981

Transcription of heat shock loci of Drosophila in a nuclear system.

We have investigated transcription in nucleic isolated from 6-18-h Drosophila melanogaster embryos. Kinetic aspects and specific products of the reaction have been analyzed; in particular, we have examined whether or not a faithful representation of an induced state, in this case the heat shock response, is maintained in the isolated nucleic. RNA polymerase II is active for at least 30 min. The combined RNA polymerase I and III activities are seen to continue synthesis for 60 min. Maximal synthesis by all enzymes is obtained in the absence of Mn2+. Transcripts from the 5S DNA have been characterized. These consist of two species, of 135 and 120 nucleotides, apparently the precursor and mature forms of 5S RNA. Extensive initiation by RNA polymerase III occurs on 5S DNA in this system. Transcription from the heat shock loci at 87A and 87Cl has been analyzed by hybridization of the newly synthesized RNA (selected by using 5'-mercuri-UTP) to plasmids containing the hsp 70 gene and adjacent regions. Only those segments of the DNA to which transcripts have been mapped in vivo hybridized with the in vitro synthesized RNA, and this transcription was observed only in nuclei isolated from heat-shocked embryos; no transcripts are detected in nuclei isolated from control embryos. These RNA species are synthesized by RNA polymerase II. Further analysis of transcription of the hsp68 gene (at locus 95D) has also been carried out. We conclude that in this system RNA polymerases II and II transcribe the chromatin template accurately and that the changes related to gene activation by heat shock are stable during nuclear isolation.

Animals↗
PubMed1981

Boerhaave syndrome. Successful conservative management in three patients with late presentation.

Three patients with Boerhaave syndrome were successfully managed with nonoperative treatment. The diagnosis was delayed 5 days in one patient and 10 days in the other two. None of the patients appeared septic. Their conditions had been misdiagnosed as myocardial infarction, pneumonia and pulmonary embolism. Treatment consisted of intravenous hyperalimentation and administration of antacids and antibiotics. Cimetidine was also used in one patient. Two patients were discharged 14 days after diagnosis and the third on the 20th hospital day. Follow-up barium swallows showed complete healing in 2 months in all three patients. Conservative management of spontaneous esophageal perforation is feasible when (1) the perforation is already 5 days old, (2) there are no signs of severe sepsis, (3) esophageal barium study shows a wide-mouthed cavity draining freely back into the esophagus, and (4) the pleural space is not contaminated. When the diagnosis is made promptly, surgical therapy remains the treatment of choice, and patients managed conservatively who show signs of sepsis should be operated on without hesitation. Follow-up esophageal evaluation should be performed to confirm complete healing and to evaluate underlying disease.

Antacids↗
PubMed1981

Risks of coronary arteriography and bypass surgery in patients with left main coronary artery stenosis.

The risk of coronary arteriography is considerably increased in patients who have left main coronary artery stenosis (LMCAS). Among 1,060 patients undergoing coronary arteriography over a three-year period, 83 were found to have LMCAS and three of these patients died (3.6 percent) during or shortly after the arteriographic procedure. Bypass surgery, however, can now be carried out at a very low risk irrespective of the degree of coronary disease present--there was no hospital mortality in 74 patients with LMCAS undergoing bypass surgery at our institution during this period. In addition to careful attention to detail, techniques that can minimize the risk of both of these procedures in patients with LMCAS include invasive hemodynamic monitoring and various pharmacologic manipulations to prevent myocardial ischemia. In a small percentage of patients, rest angina may prove refractory to inhospital medical treatment, and intraaortic balloon pumping may be necessary to stabilize the conditions of these patients before proceeding with arteriography and myocardial revascularization.

Adult↗
PubMed1981

The practice of coronary artery bypass surgery in 1980.

We obtained information from 677 cardiac surgeons in the United States on the type of practice, case load, and techniques currently used for coronary bypass operations. These surgeons collectively performed 93,000 bypass operations in 1979. Less than 25% of these procedures were done in university or federal hospitals; the majority were performed in the private sector by surgeons engaged in a single specialty group practice. The mean case load in 1979 was 137 operations per surgeon, and only 46 (6.8%) did fewer than 25 bypass operations during that year. These surgeons devote a relatively small percentage of their professional activity to other areas in thoracic surgery--the majority do not perform congenital heart surgery and two thirds devote less than 10% of their professional activity to general thoracic surgery. Compared with our previous national survey done in 1975, techniques used for bypass grafting have changed considerably over the past 5 years. An increasing number of surgeons conduct cardiopulmonary bypass with an arterial input line introduced into the ascending aorta and with a single cannula for venous drainage and do not routinely vent the left ventricle. Cold chemical cardioplegia has become the technique of choice (by 91% of surgeons) for myocardial protection, sequential bypass grafts are now widely employed, and 83.2% of surgeons perform all distal anastomoses during a single period of cardioplegic arrest.

Cardiac Surgical Procedures↗
PubMed1981

Carotid arterial disease in patients undergoing coronary artery bypass operations.

The occurrence of stroke associated with coronary artery bypass operations is approximately 2%. In an attempt to reduce this incidence some centers have proposed carotid thromboendarterectomy for symptomatic and asymptomatic carotid arterial disease in patients undergoing a coronary artery bypass operation. To obtain a better understanding of the incidence of carotid occlusive disease in candidates for the coronary bypass operation and to evaluate the practical use of a noninvasive method to screen patients preoperatively, we evaluated 102 patients preoperatively with an ultrasonic Duplex scanner; 24 studies were requested on the basis of either previous neurologic problems or the presence of a bruit and 78 patients were evaluated as part of a study protocol. In the unrequested group 6% (5/78) of the patients had a stenosis of 50% diameter reduction or more. In the requested group 54% (13/24) had a stenosis of 50% diameter reduction or more. In the postoperative phase one stroke and one transient ischemic attack were noted among the unrequested group and none in those suspected of having carotid disease on clinical grounds. Neither affected patient had a high-grade stenosis. There is little evidence to support the contention that noninvasive screening of patients free of symptoms or signs of carotid disease prior to coronary artery bypass operation is a valuable method of screening for patients who will sustain a focal neurologic event.

Carotid Artery Diseases↗
PubMed1980

Improved anesthesia for deep surface-induced hypothermia: the halothane-diethyl ether azeotrope.

The halothane-diethyl ether azeotrope was evaluated in dogs as the anesthetic agent for deep surface hypothermia with total circulatory arrest for open-heart operation. All 10 animals given azeotrope in 100% oxygen (O2) experienced atrial arrhythmias during cooling, and 1 had ventricular fibrillation prior to the completion of cooling at 18 degrees to 20 degrees C. After only 30 minutes' arrest, 8 of the 10 dogs had postoperative motor disturbances. Administering the azeotrope in 95% O2 and 5% carbon dioxide (CO2) yielded markedly improved results characterized by a rapid, smooth cooling course, easy resuscitation following circulatory arrest, and rapid rewarming, and 3 out of 10 dogs experienced mild motor disturbance after 60 minutes of circulatory arrest. This method, when compared with our standard method of ether in 100% O2, resulted in reduced blood lactates and a striking improvement in clinical status on the first postoperative morning. In limited clinical trials, infants undergoing repair of congenital cardiac defects have done well and responded as expected based on the laboratory experience. Since the results with the azeotrope in 95% O2 and 5% CO2 were at least as good as, and in several instances better than, those with the standard method employing either, the nonexplosive characteristic of the azeotrope warrants continued evaluation of this agent.

Animals↗
PubMed1980

Sensitivity of the conformation of deoxyguanosine to binding at the C-8 position by N-acetylated and unacetylated 2-aminofluorene.

The conformation of N-(deoxyguanosin-8-yl)-2-acetylaminofluorene and N-(deoxyguanosin-8-yl)-2-aminofluorene was investigated by 1H n.m.r. spectroscopy. There was rotation about the glycosyl bond and preference for either the anti or syn conformation depended on whether or not the 8-arylamino nitrogen was acetylated. The unacetylated adduct existed preferentially in the anti form and the acetylated adduct existed preferentially in the alternate syn form. There was also rotation about the backbone C4' -C5' bond. The unacetylated adduct was mainly in the gauche-gauche conformation about C4'-C5', while the acetylated adduct was mainly in the alternate gauche-trans/trans-gauche form. Using space filling models with the conformation of the unacetylated adduct conserved in the helix, a possible structure of modified DNA was proposed which had less perturbation of the helix than that of the acetylated adduct. This was consistent with single strand endonuclease hydrolysis data. The acetylated and unacetylated adducts may cause entirely different types of local conformational changes in DNA because of major differences in interactions between the base and the sugar moiety at the modified nucleoside level.

2-Acetylaminofluorene↗