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Biomedical subjects

S P Nolan

Publications and source records attributed to S P Nolan.

At least 19 recordsLinked to original sources

Convenient and efficient Suzuki-Miyaura cross-coupling catalyzed by a palladium/diazabutadiene system.

[structure: see text]. A Pd(OAc)2/diazabutadiene system has been developed for the catalytic cross-coupling of aryl halides with arylboronic acids. A combination of the diazabutadiene DAB-Cy (1, N,N'-dicyclohexyl-1,4-dizabutadiene) and Pd(OAc)2 was found to form an excellent catalyst for the Suzuki-Miyaura cross-coupling of various aryl bromides and activated aryl chlorides with arylboronic acids.

Journal Article↗

A modular synthetic approach toward exhaustively stereodiversified ligand libraries.

[structure] This report describes a modular approach to the synthesis of stereodiversified natural product-like libraries. Monomers 2 and 3 were coupled in parallel by silyl-tethered olefin metathesis to generate all 16 stereoisomers of cis-enediols 1. All 16 stereoisomers were incorporated into chimerae having flanking peptidic segments. These chimerae exhibited a broad range of hydrophobicities, raising the possibility that stereochemical variation might be used to tune the pharmacologic properties of small molecules.

Alkenes↗

Studies of the synthesis and thermochemistry of coordinatively unsaturated chelate complexes (eta 5-C5Me5)IrL2 (L2 = TsNCH2CH2NTs, TsNCH2CO2, CO2CO2).

A comparative synthetic, structural, and thermochemical study on a series of chelate complexes containing the fragment (eta 5-C5Me5)Ir [(eta 5-C5Me5)Ir(TsNCH2CH2NTs) (1), (eta 5-C5Me5)Ir(TsNCH2CO2) (2), (eta 5-C5Me5)Ir(CO2CO2) (3)] was performed to clarify the roles of carboxylato and sulfonamido ligands. Whereas 1 and 2 are monomeric in solution and in the solid state, 3 appears to exist as an oligomer or polymer, (3)n, which can be broken up by addition of a ligand L such as a phosphine, CO, or 2-methoxypyridine to form (eta 5-C5Me5)Ir(L)(CO2CO2) (6). The synthesis of (3)n from [(eta 5-C5Me5)IrCl(mu-Cl)]2 required the use of silver oxalate in CH3CN, but if other solvents were used, the bridging oxalato complex (eta 5-C5Me5)IrCl(mu-eta 2-eta 2-C2O4)ClIr(eta 5-C5Me5) (7) was obtained and identified by X-ray diffraction. Enthalpies for reaction of THF-soluble monomers 1 and 2 with PMe3 were determined to be -28.7(0.5) and -28.5(0.4) kcal mol-1, respectively. The oligomerization behavior of 3 may be a result of reduced sigma- or pi-donation of carboxylato ligands compared to N-tosylamido ligands, because the values for nu CO in oxalato and bissulfonamido complexes 6-CO and (eta 5-C5Me5)Ir(CO)(TsNCH2CH2NTs) (4-CO) were 2064 and 2042 cm-1, respectively.

Journal Article↗

Interventions to reduce decibel levels on patient care units.

The University of Virginia Health System inpatient satisfaction survey identified noise as the most important irritant to surgical inpatients. Analysis of the level and pattern of noise on patient floors and intensive care units was done with baseline measurements followed by then two separate interventions: 1) education of nursing and physician staff 2) closing patient room doors. A decibel meter (M-27 Dosimeter) recorded the noise level over 24 hours. Patients doors were open in the initial measurements. Next, three 1-hour education sessions were conducted by a surgeon and nursing supervisor to review noise-reduction strategies with the staff. These included using pagers in vibrate mode, minimizing overhead announcements, and conducting nurse reports and physician teaching sessions in classrooms away from the nurses' station. Finally, the doors were closed except as visitors and staff entered the room. Little impact was seen from staff education. Closing patient doors on surgical floors decreased noise an average of 6.0 dB, a change that patients can readily perceive. Conversely, intensive care unit patients are exposed to more noise with closed doors, presumably because most noise emanates from equipment within the room. A policy of closing patient floor room doors may increase patient satisfaction.

Communication↗

Is vertical vein ligation necessary in repair of total anomalous pulmonary venous connection?

BACKGROUND: In the repair of total anomalous venous connection, vertical vein ligation is recommended to eliminate left-to-right shunting. However, the small left heart chambers may not always tolerate the immediate increase in blood flow after combined repair and vein ligation. METHODS: A retrospective review of 23 infants and children undergoing correction of total anomalous pulmonary venous connection was undertaken to determine whether vertical vein ligation is a necessary component of successful surgical repair. In 14 patients this vein was ligated, whereas in 9 it was left patent. Six patients who underwent ligation and 5 who did not had pulmonary venous obstruction before operation. RESULTS: The operative mortality rate was 36% (5 of 14 patients) for the ligated group compared with 0% (0 of 9 patients) for the nonligated group (p = 0.06). All deaths occurred in patients with preoperative obstruction and a low mean left atrial pressure, and four of the deaths were directly attributable to left heart failure. Follow-up echocardiography in patients in whom the vertical vein was not ligated revealed adequate cardiac function and no residual left-to-right flow through the previously patent venous conduit. CONCLUSION: Vertical vein ligation during the repair of total anomalous pulmonary venous connection is not routinely necessary and actually may be undesirable in patients with preoperative obstruction, in whom the left heart chambers are particularly small.

Cardiac Surgical Procedures↗

Reflections on the evolution of cardiopulmonary bypass.

The concept of cardiopulmonary bypass is more than a century old. Although the first clinical application occurred in 1953, there were great deficits in knowledge and materials that had to be overcome before we could achieve the outcomes of cardiac surgery that we have today.

Cardiac Surgical Procedures↗

Synthesis and ligand binding of eta(6)-(2beta-carbomethoxy-3beta-phenyltropane) transition metal complexes.

The transition metal complexes [eta(6)- (2beta-carbomethoxy-3beta-phenyltropane)]tricarbonylchromium (3) and [eta(6)-(2beta-carbomethoxy-3beta-phenyltropane)] [eta(5)-(pentamethylcyclopentadienyl)]ruthenium(II)triflate (4) were synthesized from 2beta-carbomethoxy-3beta-phenyltropane (2, WIN 35,065) to further elucidate the influence of substituents on the 3beta-aryl on the affinity of the ligand for cocaine-binding sites at the dopamine transporter. The compounds were tested for their ability to displace bound [(3)H]WIN 35,428 (5) from rat caudate putamen tissue and for their ability to inhibit [(3)H]dopamine uptake. The binding affinity for 3 was 2-fold greater than those observed for cocaine (1) and 2, while the binding affinity for 4 was found to be 100-fold less than those of 1 and 2. In addition, 3 was equipotent with 1 and 2 in [(3)H]dopamine uptake inhibition studies, while 4 was 10-fold less potent. The potencies of the complexes 3 and 4 correlated well with the structure-activity relationships of other 2beta-carbomethoxy-3beta-aryltropane derivatives. These data further support a pharmacophore model in which the region occupied by the aryl ring is a lipophilic pocket with electropositive character.

Animals↗

Transatrial approach to posterior postinfarct ventricular septal defects.

Repair of posterior postinfarct ventricular septal defects via the transinfarct left ventriculotomy is technically challenging and can be associated with significant morbidity. A transatrial approach avoids incising through the acutely infarcted myocardium and, in selected cases, offers a safe and reliable repair of these defects.

Cardiac Surgical Procedures↗

Reduction of femoral arterial bleeding post catheterization using percutaneous application of fibrin sealant.

The number of cardiac catheterizations performed yearly is growing with correspondingly increasing amounts of morbidity, complications, and hospital costs. This study suggests that fibrin sealant instillation via an arterial sheath at the completion of femoral catheterization may improve hemostasis. Results using fibrin sealant in 12 unheparinized dogs documented significant reductions (McNemar's exact test) versus control for groin ecchymoses (1 versus 8, P = .008) and radiolabeled hematoma formation (0 versus 7, P = .016). Also swelling was less in the fibrin sealant treated groins when compared to control groins (1 versus 6, P = .125), but failed to reach statistical significance. Results in eight heparinized dogs (activated clotting time 374 +/- 22, mean +/- SEM) revealed a statistically significant reduction in signs of gross bleeding in the fibrin sealant-treated groins (1 versus 8, P = .016). This method may contribute to reduced morbidity, complications, and length of hospitalization. It may also allow for earlier patient mobilization after cardiac catheterization.

Administration, Cutaneous↗

General surgical complications can be predicted after cardiopulmonary bypass.

OBJECTIVE: The authors review the general surgical complications of cardiopulmonary bypass, including newer procedures such as heart and lung transplantation, to identify patients at higher risk. SUMMARY BACKGROUND DATA: Although rare, the general surgical complications of cardiopulmonary bypass are associated with high mortality. The early identification of patients at increased risk for these complications may allow for earlier detection and treatment of these problems to reduce mortality. METHODS: A retrospective review was performed of 1831 patients undergoing cardiopulmonary bypass from 1991 to 1993. This was done to identify factors that significantly contributed to an increased risk of general surgical complications. RESULTS: Factors associated with an increased risk of general surgical complications included prolonged cardiopulmonary bypass (p < 0.005) and intensive care unit stay (p < 0.002), occurrence of arrhythmias (p < 0.001), use of inotropic agents (preoperatively or postoperatively p < 0.001), insertion of the intra-aortic balloon pump (preoperatively p < 0.005, postoperatively p < 0.001), use of steroids (p < 0.001), and prolonged ventilator support (p < 0.001). Multivariate analysis identified use of the intra-aortic balloon pump (p < 0.001) as the strongest predictor of the general surgical complications of cardiopulmonary bypass. A variety of factors not contributing significantly to an increased risk also were identified. CONCLUSIONS: Factors indicative of or contributing to periods of decreased end-organ perfusion appear to be significantly related to general surgical complications after cardiopulmonary bypass.

Aged↗

Mechanism of mitral leaflet excursion.

The factors that influence the extent of mitral leaflet opening (MLO) and closure (MLC) have not been defined. We hypothesized that left ventricular (LV) systolic function determines the rate of increase of the early diastolic left atrial (LA)-LV pressure gradient, which is responsible for the extent of MLO, and also the rate of change of the early systolic LV-LA pressure gradient, which determines the degree of MLC. Accordingly, global LV function was changed by altering left main coronary artery flow with LA pressure held relatively constant. LV end-systolic dimension and peak positive LV rate of pressure development (dP/dt) correlated best with the degrees of MLO and MLC, with average correlation coefficients of 0.88 and 0.68, and 0.86 and 0.72, respectively. Although transsecting the submitral apparatus resulted in flailing of the mitral leaflets during normal LV systolic function, the extents of MLO and MLC during LV systolic dysfunction were still influenced by LV systolic function. It is concluded that LV systolic function determines the extent (both opening and closure) of mitral leaflet excursion.

Animals↗

The search for standards.

The International Organization for Standardization (ISO) assigned the responsibility for developing valve standards to its technical committee on surgical implants. A sub-committee on cardiovascular implants and the working group for heart valves were formed more than 20 years ago. The working group has learned a great deal, not only from its experience with ISO, but most of all from the collaboration of its international experts representing science, engineering and manufacturing. The first valve standard was published in 1984, revised in 1989, and the next revision will probably be published in 1995. After the formation of this ISO working group in 1972, the U.S. Food and Drug Administration (FDA) developed regulations for the premarket approval of heart valves in the United States. The European Committee for Standardization (CEN) was subsequently formed and appointed a working group to develop heart valve standards for Europe. It rapidly became apparent that the lack of co-ordination and communication of three separate organizations writing documents with different requirements and tests would lead to inconsistent and conflicting requirements. The ultimate outcome could have been a threat to public welfare by limiting the availability of medical devices. The commitment to the harmonization of standards by CEN and ISO, and the recent FDA policy to participate actively in standards development, have greatly improved this situation. Past errors, omissions and inappropriate attitudes have often slowed the standards process or have resulted in incomplete standards. This learning experience, while painful, should point the way to more timely and complete standards development in the future.

Biomedical Engineering↗

High speed cine-radiographic study of aortic valve leaflet motion.

The leaflets of the aortic valve move extremely rapidly during opening and closing. To analyse this movement, radiopaque markers were placed on the aortic valves of four dogs during cardiopulmonary bypass. One to five months later the dogs were studied using x-ray, and the marker motion was recorded on cine-film at 500 frames/second. Simultaneous aortic pressure varied from 70/30 to 188/152 mmHg and heart rate from 33 to 150 bpm. Analysis of 19 systolic periods and 2500 cine-frames indicated that leaflet motion occurred in four phases: 1--rapid movement during initial opening, 2--a little movement near maximal excursion, 3--a slow movement during early closing and 4--a rapid movement to complete closure. Phases 1 and 4 averaged 17.6 and 16.5 msec respectively, and were independent of heart rate, whereas the length of phases 2 and 3 varied with heart rate. The leaflets moved 82% of their maximum excursion during rapid opening and 53% during rapid closure. Leaflet curvature reversed in both the radial and the circumferential directions during opening. The leaflet profile in the radial direction changed as follows: during rapid opening, the belly of the leaflet moved outward, first causing the leaflet to straighten and then to conform to the profile of blood flow. During closure the belly of the leaflet moved centrally, causing the leaflet to curve toward the ventricle. The leaflet profile in the circumferential direction indicated that during opening the midpoint of the leaflet leads the motion towards the aortic wall.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Distribution of low density lipoprotein in the branch and non-branch regions of the aorta.

Atherosclerosis occurs focally in branch segments of the artery. Understanding why these segments are more susceptible to the development of the disease is at the root of understanding atherogenesis. We investigated accumulation of low density lipoprotein (LDL) in the branch and non-branch regions of the aorta to determine why the disease develops in branch regions. Abdominal aortas and their major branches were harvested from 36 rabbits. Rabbit LDL was prepared from whole blood and radiolabeled with 125I. The aorta was incubated with radiolabeled LDL in the lumen at 37 degrees C, under intraluminal pressure of 2-3 mmHg, for 1 h. Disks of 1.8 mm diameter were punched from the branch and non-branch regions of the aorta, cryosectioned and the sections counted in a gamma counter. Protein bound radioactivity was determined by TCA precipitation. LDL accumulation was highest towards the aortic intima and declined sharply towards the media. LDL accumulation at any given depth was higher in the branch than non-branch region. LDL accumulation in the intimal-medial sections was 87% higher in the branch than non-branch region. Total LDL accumulation in the branch was almost twice that in the non-branch region. Mean LDL accumulation was also greater in the branch than non-branch region. The aorta was significantly thicker at the branch. LDL distribution profiles indicate that LDL is present in a greater concentration and over a greater depth in the branch than non-branch region. The tendency of the branch region to accumulate LDL in greater amounts may explain its susceptibility to atherosclerotic lesion development.

Animals↗