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Biomedical subjects

J M Duncan

Publications and source records attributed to J M Duncan.

At least 19 recordsLinked to original sources

Origin of a new Phytophthora pathogen through interspecific hybridization.

Plant disease epidemics resulting from introductions of exotic fungal plant pathogens are a well known phenomenon. An associated risk-that accelerated pathogen evolution may be occurring as a consequence of genetic exchange between introduced, or introduced and resident, fungal pathogens-is largely unrecognized. This is, in part, because examples of natural, interspecific hybridization in fungi are very rare. Potential evolutionary developments range from the acquisition of new host specificities to emergence of entirely new pathogen taxa. We present evidence from cytological behavior, additive nucleotide bases in repetitive internal transcribed spacer regions of the rRNA-encoding DNA (rDNA), and amplified fragment length polymorphisms of total DNA that a new, aggressive Phytophthora pathogen of alder trees in Europe comprises a range of heteroploid-interspecific hybrids involving a Phytophthora cambivora-like species and an unknown taxon similar to Phytophthora fragariae. The hybrids' marked developmental instabilities, unusual morphological variability, and evidence for recombination in their internal transcribed spacer profiles indicates that they are of recent origin and that their evolution is continuing. The likelihood of such evolutionary events may be increasing as world trade in plants intensifies. However, routine diagnostic procedures currently in use are insufficiently sensitive to allow their detection.

Biological Evolution

Right atrial bypass grafting for central venous obstruction associated with dialysis access: another treatment option.

PURPOSE: Central venous obstruction is a common problem in patients with chronic renal failure who undergo maintenance hemodialysis. We studied the use of right atrial bypass grafting in nine cases of central venous obstruction associated with upper extremity venous hypertension. To better understand the options for managing this condition, we discuss the roles of surgery and percutaneous transluminal angioplasty with stent placement. METHODS: All patients had previously undergone placement of bilateral temporary subclavian vein dialysis catheters. Severe arm swelling, graft thrombosis, or graft malfunction developed because of central venous stenosis or obstruction in the absence of alternative access sites. A large-diameter (10 to 16 mm) externally reinforced polytetrafluoroethylene (GoreTex) graft was used to bypass the obstructed vein and was anastomosed to the right atrial appendage. This technique was used to bypass six lesions in the subclavian vein, two lesions at the innominate vein/superior vena caval junction, and one lesion in the distal axillary vein. RESULTS: All patients except one had significant resolution of symptoms without operative mortality. Bypass grafts remained patent, allowing the arteriovenous grafts to provide functional access for 1.5 to 52 months (mean, 15.4 months) after surgery. CONCLUSION: Because no mortality directly resulted from the procedure and the morbidity rate was acceptable, this bypass grafting technique was adequate in maintaining the dialysis access needed by these patients. Because of the magnitude of the procedure, we recommend it only for the occasional patient in whom all other access sites are exhausted and in whom percutaneous dilation and/or stenting has failed.

Adult

Concomitant occlusive disease of the coronary arteries and great vessels.

BACKGROUND: Although an increasing number of elderly and high-risk patients, including those with generalized atherosclerosis, are undergoing coronary revascularization, few reports exist regarding the management of patients who have both occlusive disease of the great vessels and coronary artery disease. METHODS: Between 1972 and 1996, 31 consecutive patients (mean age, 56.5 years; 74% men) with multivessel coronary artery disease and symptomatic occlusive disease of the great vessels (25 single-vessel, 80.6%; 6 multiple-vessel, 19.4%) had 40 great vessels reconstructed by transthoracic bypass (n = 17, 42.5%), transthoracic endarterectomy (n = 8, 20%), or extrathoracic bypass (n = 15, 37.5%). All patients had simultaneous coronary artery bypass grafting (mean, 2.6 grafts per patient), and 8 patients had 10 distal carotid bifurcation endarterectomies (6 staged, 4 simultaneous). RESULTS: The early primary patency rate was 100%, and symptoms resolved completely in all 31 patients. There was 1 in-hospital death (3.2%) in a patient who had a respiratory arrest 11 days after operation. Perioperative morbidity included two myocardial infarctions (6.5%) and one opposite-hemisphere, embolic stroke (3.2%). Long-term follow-up of the 30 survivors (167.4 patient-years; mean, 5.6 years per patient) documented 5- and 10-year actuarial survival rates of 88.6% and 60.4%, respectively, with a 100% late brachiocephalic primary patency rate. Ten-year actuarial rates of freedom from the following events were as follows: death, 60.4%; myocardial infarction, 82.5%; stroke, 90.9%; percutaneous transluminal coronary angioplasty or redo coronary artery bypass grafting, 95.2%; and vascular operation or amputation, 78.4%. CONCLUSIONS: Depending on the anatomic distribution of the disease, an integrated approach to great vessel reconstruction that incorporated transthoracic and extrathoracic approaches and techniques of endarterectomy and bypass resulted in few adverse outcomes and excellent long-term patency. Simultaneous revascularization of the great vessels and coronary arteries can produce immediate and long-term, symptom-free outcome with acceptably low operative risk.

Aged

The Information Commons: a model for (physical) digital resource centers.

Since its planning, construction, and opening in 1996, the Information Commons, located in The University of Iowa's Hardin Library for the Health Sciences, has served as a common ground for self-directed learning, information research, hands-on class sessions, and multimedia development. Initiatives launched from the Information Commons not only have helped increase the visibility of Hardin Library as an environment well equipped to support traditional research and education needs, but have promoted the library as a campus leader and viable partner in planning and delivering digital technologies effectively. Ongoing initiatives have focused on better integrating the library's services and resources with the curricula and research needs of the university's health sciences units. This paper describes the facility, its programmatic elements, and its impact on education, communication, and technology trends in an academic health sciences setting. Particular attention is paid to initiatives launched during the first two years of operation. This paper also discusses plans for expansion of the facility.

Budgets

Is an integrated approach warranted for concomitant carotid and coronary artery disease?

BACKGROUND: The management of patients with severe, concomitant coronary and carotid artery occlusive disease is controversial. METHODS: Between 1975 and 1996, 512 patients (mean age, 64.9 years; 70% male) were admitted for coronary revascularization; 316 (61.7%) had asymptomatic, severe carotid disease (stenosis > 70%) and 196 (38.3%) had symptomatic carotid disease (159 [31.1%] with transient ischemia and 37 [7.2%] with completed stroke). In group 1, coronary revascularization and carotid endarterectomy were simultaneously performed in 255 patients (49.8%) with unstable angina. In group 2 (staged approach), carotid endarterectomy was performed before coronary revascularization in 257 patients (50.2%) without unstable angina. RESULTS: Before 1986, the incidence of stroke and death was greater in group 1 (n = 149) than in group 2 (n = 156) (14 [9.4%] versus 4 [2.6%]; p < 0.01). Since 1986, outcomes in group 1 (n = 106) and group 2 (n = 101) have been similar for stroke (2 [1.9%] versus 2 [2.0%]), death (4 [3.8%] versus 3 [3.0%]), and myocardial infarction (4 [3.8%] versus 5 [5.0%]). Significant univariate and multivariate predictors of adverse outcome were primarily heart-related (reoperation, intraaortic balloon use, ejection fraction < 0.50, and angina grade 4 for death; age > 70 years and congestive heart failure for stroke). CONCLUSIONS: Despite highly selected populations, contemporary surgical results do not indicate that staged treatment of severe, concomitant coronary and carotid artery occlusive disease has an advantage over simultaneous treatment. Advances in myocardial protection and perioperative hemodynamic management may account for the low incidences of stroke and death in these operations.

Adult

The tigA gene is a transcriptional fusion of glycolytic genes encoding triose-phosphate isomerase and glyceraldehyde-3-phosphate dehydrogenase in oomycota.

Genes encoding triose-phosphate isomerase (TPI) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) are fused and form a single transcriptional unit (tigA) in Phytophthora species, members of the order Pythiales in the phylum Oomycota. This is the first demonstration of glycolytic gene fusion in eukaryotes and the first case of a TPI-GAPDH fusion in any organism. The tigA gene from Phytophthora infestans has a typical Oomycota transcriptional start point consensus sequence and, in common with most Phytophthora genes, has no introns. Furthermore, Southern and PCR analyses suggest that the same organization exists in other closely related genera, such as Pythium, from the same order (Oomycota), as well as more distantly related genera, Saprolegnia and Achlya, in the order Saprolegniales. Evidence is provided that in P. infestans, there is at least one other discrete copy of a GAPDH-encoding gene but not of a TPI-encoding gene. Finally, a phylogenetic analysis of TPI does not place Phytophthora within the assemblage of crown eukaryotes and suggests TPI may not be particularly useful for resolving relationships among major eukaryotic groups.

Amino Acid Sequence

Effects of donor position on harvested lung quality.

Potential lung donors are frequently maintained in one position for prolonged periods of time prior to harvest. This study was designed to determine if the effects of gravity induced by maintaining an animal model in the supine position for 24 hr would have adverse effects on the harvested lung. Group 1 pigs were anesthetized, instrumented, mechanically ventilated, and the lungs harvested within 90 min. Group 2 pigs were anesthetized, instrumented, and mechanically ventilated in an identical manner then maintained in the same dorsal-spinal recumbency position for 24 hrs. Hemodynamic and respiratory parameters were stable and not statistically different between the two groups for the baseline and 1 hr time period measurements. There were no significant differences between the two groups for shunt fractions, wet/dry ratios, blood flow distribution, or flush solution distribution. We conclude that in anesthetized pigs there is no evidence that routine repositioning protocols improve blood flow distribution, shunting, or dependent edema.

Animals

Carotid endarterectomy. Results in asymptomatic and symptomatic patients.

Objective evidence of the benefit of carotid endarterectomy in preventing stroke and its significant sequelae has recently been demonstrated by prospective trials. The salutary results depend on meeting strict operative outcome criteria as established by the American Heart Association. We retrospectively analyzed 265 consecutive carotid endarterectomies performed in 248 patients during 1 year at our institution. The perioperative mortality rate was 0; late mortality occurred 6 months postoperatively in 1 of 2 patients who experienced a perioperative stroke. The combined perioperative mortality and stroke rate was 0.8%. The combined mortality and stroke rate in patient subgroups was 0.7% (1/151) for asymptomatic patients, 1.6% (1/64) for symptomatic patients who had presented with a transient ischemic attack, and 0% (0/50) for symptomatic patients who had presented with a completed stroke. We conclude that the objective postoperative benefits of carotid endarterectomy in treating extracranial cerebrovascular disease can be achieved with low perioperative patient morbidity.

Carotid Stenosis

Management of mitral valve stenosis in pregnancy: case presentation and review of the literature.

Severe mitral stenosis is a challenging complication in pregnancy. A case is described in which mitral valve replacement was undertaken immediately following caesarean section at 34 weeks' gestation. A review of the literature discusses the evolution of treatment approaches for mitral stenosis in pregnancy, including open mitral commissurotomy and percutaneous mitral commissurotomy with the use of balloon catheters. With balloon procedures, potential risks to the fetus are minimized because the abdomen and pelvis are shielded. In addition, the use of adjunct transesophageal echocardiography shortens fluoroscopic time. In the case described, neither open nor percutaneous mitral commissurotomy were viable options because of moderate-to-severe mitral regurgitation and a heavily calcified valve. This is one of few such cases reported in the literature to date.

Adult

Effect of IgM-positive crossmatches on survival in heart transplant recipients.

To determine whether an IgM-positive crossmatch adversely affects the results of heart transplantation, we conducted a retrospective study of 125 orthotopic heart transplant recipients. A direct donor-recipient crossmatch was performed retrospectively on sera from all patients by the standard National Institutes of Health (NIH) method and the antihuman globulin (AHG) procedure. The patients were then divided into 3 groups as follows. Group 1 comprised 110 patients with a negative NIH and AHG crossmatch (control group). Group 2 comprised 5 patients with a positive NIH crossmatch and a negative AHG crossmatch. Group 3 comprised 10 patients with positive NIH and AHG crossmatches. All positive crossmatches in group 3 patients converted to negative after treatment of sera with dithioerythritol, indicating that the initial result was due to IgM antibodies. All patients received standard immunosuppressive treatment. An IgM-positive crossmatch did not affect the number or severity of rejection episodes among the 3 groups, nor did it have an effect on the incidence of infection. Whereas coronary artery disease was detected by angiography in 16 of 110 patients (14.6%) in group 1 and in 1 of 10 patients (10%) in group 3 (P = NS), no patient in group 2 was affected. Actuarial survival at 1 and 2 years post-transplant was significantly better for patients with an IgM-positive crossmatch (group 2) (100% survival at 2 years) than for patients with a negative crossmatch (group 1) (73% at 1 year and 71% at 2 years, P < 0.05). Based on our study, the effect of an IgM-positive crossmatch on survival is difficult to interpret because of the small sample size. An IgM-positive crossmatch, however;did not appear to have a deleterious effect on survival. It may be that the IgM antibody has an immunoregulatory role. A larger series of patients with positive crossmatches and longer follow-up will be necessary to evaluate the importance of these results.

Actuarial Analysis

The Medicare Participating Heart Bypass Demonstration Project in Houston, Texas. The experience of St. Luke's Episcopal Hospital, Texas Heart Institute, and CardioVascular Care Providers, Inc.

While passage of a health care bill remains uncertain, the structure of health care in the United States is nonetheless changing rapidly. In some cases, physicians and hospitals are working more closely with one another to provide high-quality care at lower costs. Patients, physicians, hospitals, and insurers (including the Federal government) can all benefit from such an arrangement. We review here the experience with a program of bundled-free (physician and hospital) cardiovascular care for Medicare patients at the Texas Heart Institute at St. Luke's Episcopal Hospital in Houston, Texas.

Adolescent

Improved survival after extended bridge to cardiac transplantation.

In the past, left ventricular assist device (LVAD) support was frequently plagued by complications; thus, bridge to transplantation times were kept short. Increasing evidence suggests that extended bridging provides greater benefit due to improved end-organ perfusion and, thus, generally improved physical condition. To assess whether extended bridging translates into improved long-term survival after transplantation, we reviewed our experience with the HeartMate 1000 IP LVAD (Thermo Cardiosystems, Inc, Woburn, MA). Since January 1988, 19 patients (mean age, 45 +/- 9 years) have undergone extended bridging (mean time, 106 +/- 57 days). Their mean weight was 82 +/- 16 kg, and their mean body surface area was 2.0 +/- 0.2 m2. We define "extended" as the length of support necessary for systemic organ recovery after prolonged heart failure. During support, average pump flow indices ranged from 2.3 to 3.3 L.min-1.m-2, and all patients underwent physical rehabilitation. Between the time of LVAD implantation and explantation, the mean serum creatinine value decreased from 1.63 +/- 0.6 to 1.25 +/- 0.6 mg/dL (p = not significant), and the mean serum total bilirubin value decreased from 2.8 +/- 2.0 to 0.63 +/- 0.11 mg/dL (p < 0.05). All but 1 patient improved from New York Heart Association class IV to class I. Device-related complications were minimal. Twelve control patients ("de facto randomized") who did not receive the LVAD also were evaluated: actuarial survival at 1 year was 0% (p < 0.05); 3 (25%) underwent transplantation and died within 2 months; 9 (75%) died before transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Improved multiorgan function after prolonged univentricular support.

Eleven cardiac transplant candidates (all male; mean age, 43.3 years) with multiorgan (hepatic, pulmonary, and/or renal) dysfunction were sustained for prolonged periods (> 30 days) with the HeartMate (Thermo Cardiosystems, Inc, Woburn, MA) left ventricular assist device. We evaluated the effect of extended support on end-organ recovery and on the ultimate outcome of cardiac transplantation. In addition to cardiac failure, 9 patients had hepatic dysfunction, 8 had pulmonary dysfunction, and 6 had renal dysfunction (4 of whom required hemodialysis before left ventricular assist device support). Mean duration of support was 115 days (range, 31 to 233 days). All patients underwent successful transplantation; 10 of these patients survived a mean of 24 months. One patient, who had required hemodialysis and ventilatory support during and after support, experienced progressive multiorgan failure and died 7 weeks after transplantation. Two late deaths after transplantation were unrelated to the device. Overall, patients experienced improvement in cardiac functional class status, and most participated in cardiac rehabilitation programs before transplantation. During left ventricular assist device support, hepatic function returned to normal in 8 patients, pulmonary function recovered in 7, and renal function returned to normal in 4. One patient who required hemodialysis underwent renal transplantation after cardiac transplantation and had complete recovery of renal function. In the current era of donor shortages, gravely ill patients can benefit from a strategy of prolonged left ventricular assist device support. This strategy has proved safe, has allowed for reversal of multiorgan dysfunction, and has produced healthier transplant candidates.

Adult

Peripheral organ perfusion augmentation during left ventricular failure. A controlled bovine comparison between the intraaortic balloon pump and the Hemopump.

Despite the use of inotropic therapy and the intraaortic balloon pump (IABP), inadequate peripheral organ perfusion and subsequent multiorgan failure from left ventricular dysfunction is a major cause of death following cardiac surgery. To compare the end-organ perfusion provided by the IABP with that of the recently developed Hemopump Cardiac Assist System, blood flow from visceral organs was measured by ultrasonic flow probes during separate periods of support with each of these pumps. Ten calves underwent coronary artery ligations with beta-receptor blockade; hemodynamic parameters were recorded before the induction of failure, during unsupported cardiac failure, and during Hemopump and IABP support. Improvement in mean cardiac output, mixed venous oxygen saturation, and pulmonary artery wedge pressure was significantly greater (p < 0.05) during Hemopump support than during IABP support. Renal artery flow was significantly greater during Hemopump support (276 +/- 74.2 cc/min) than during IABP support (164 +/- 79.6 cc/min). Hepatic artery flow was significantly greater during Hemopump support (34.7 +/- 25.7 cc/min) than during IABP support (24.4 +/- 18.9 cc/min), and portal vein flow was significantly greater during Hemopump support (1588 +/- 315 cc/min) than IABP support (1259 +/- 310 cc/min). There were no significant differences, however, between carotid artery flow during Hemopump support (292 +/- 171 cc/min) and that during IABP support (317 +/- 204 cc/min). We conclude that renal, hepatic, and mesenteric perfusion provided by the nonpulsatile Hemopump is superior to that of the IABP in this bovine model of left ventricular failure. Therefore, the Hemopump may be more effective in preventing multiorgan failure during recovery of ventricular function.

Animals

Immunochemical identification of human endothelial cells on the lining of a ventricular assist device.

We are studying the biologic (pseudointimal) lining that forms in the HeartMate (Thermo Cardiosystems, Inc.; Woburn, Massachusetts, USA), a left ventricular assist device with a pusher-plate blood pump, housed in solid titanium with uniquely textured blood-contacting surfaces. Sintered titanium microspheres cover the rigid surface, and integrally textured polyurethane lines the flexing diaphragm. The texture of the blood-contacting surfaces is designed to encourage formation of a biologic pseudointimal lining, which greatly reduces the risk of thromboembolic complications. We performed immunochemical analyses to characterize precisely the pseudointimal lining. Samples were taken from 2 explanted pumps; 1 had supported a patient for 132 days and the other, 189 days. The samples were cultured to detect factor-VIII-related antigen (von Willebrand factor), acetyl low-density lipoprotein receptors, smooth-muscle-cell actin, and surface adhesion molecules specific for monocytes/macrophages. Macrophage cells were predominant in both pumps, but in the 2nd pump, cultures from the center of the diaphragm were positive for acetyl low-density lipoprotein receptor and von Willebrand factor, indicating the presence of endothelial cells. We believe that blood-borne endothelial cells or endothelial cell precursors were deposited on the blood-contacting surfaces, which is an important clinical finding with regard to lowering the risk of thromboembolic complications and reducing the need for systemic anticoagulation in long-term left ventricular assist device patients.

Actins

Zinc fingerprinting for Phytophthora species: ZIF markers.

We have assessed the potential of using zinc finger markers for identification of fungal species using Phytophthora as a model organism, since it is particularly difficult to classify. The results show that such markers are suitable for species identification of Phytophthora but do not appear to aid strain identification within species.

Base Sequence