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Biomedical subjects

E L Jones

Publications and source records attributed to E L Jones.

At least 19 recordsLinked to original sources

Development of a water-soluble, sulfated (1-->3)-beta-D-glucan biological response modifier derived from Saccharomyces cerevisiae.

This report describes a method for the solubilization of micro-particulate (1-->3)-beta-D-glucan. Insoluble glucan is dissolved in methyl sulfoxide and urea (8 M) and partially sulfated at 100 degrees. The resulting water-soluble product is called glucan sulfate. The conversion rate is 98%, and the preparation is endotoxin free as determined by the Limulus lysate procedure. Glucan sulfate is composed of 34.06% C, 6.15% H, 50.30% O, 5.69% S and 3.23% N, and has a repeating unit empirical formula of (C6H10O5)8.3 SO3NH4+.4 H2O, suggesting that, on the average, a sulfate group is substituted on every third glucose subunit along the polymer. Molecular weight averages, polydispersity, and intrinsic viscosity were determined by aqueous high-performance size-exclusion chromatography (HPSEC). Two polymer peaks were resolved. Peak 1 (Mw = 1.25 x 10(6) g/mol) represents < 1% of the total polymer mass. Peak 2 (Mw = 1.45 x 10(4) g/mol) comprises > 99% of polymers. 13C NMR spectroscopy confirmed the beta-(1-->3) interchain linkage. In solution, glucan sulfate polymers self-associate in a triple helix. Glucan sulfate stimulates murine bone marrow proliferation following intravenous administration. The ability to prepare a immunologically active, water-soluble (1-->3)-beta-D-glucan preparation will greatly enhance the clinical utility of this class of compounds.

Animals

Emergency coronary artery bypass surgery for failed percutaneous coronary angioplasty. A 10-year experience.

Six hundred ninety-nine patients have required emergency coronary artery bypass after failed elective percutaneous coronary angioplasty during the decade September 1980 through December 1990. This represents 4% of 9860 patients having 12,146 elective percutaneous coronary angioplasty procedures during this interval. Emergency coronary artery bypass was required for acute refractory myocardial ischemia in 82%. Hospital mortality rate for all patients was 3.1%; 3.7% in patients with refractory myocardial ischemia but 0.8% in patients without refractory myocardial ischemia, p = 0.08. Postprocedural Q-wave myocardial infarctions were observed in 21% versus 2.4%, p less than 0.0001, and intra-aortic balloon pumping was required in 19% with versus 0.8% without refractory myocardial ischemia, p less than 0.0001. Multivessel disease, p = 0.004, age older than 65 years, p = 0.005, and refractory myocardial ischemia, p = 0.08, interacted to produce the highest risk of in-hospital death. Follow-up shows that there have been 28 additional late deaths, including 23 of cardiac causes for a 91% survival at 5 years. Freedom from both late death and Q-wave myocardial infarction at 5 years was 61%. In the group going to emergency coronary artery bypass with refractory myocardial ischemia, the late cardiac survival was 90%, and in those without ischemia, 92% at 5 years, p = not significant. The MI--free survival in the group with refractory ischemia, however, was 56% versus 83% in the group without ischemia, p less than 0.0001. Multivariate analysis showed the highest late event rates for patients with Q-wave myocardial infarction at the initial emergency coronary artery bypass, age older than 65 years, angina class III or IV, and prior coronary bypass surgery. In spite of a continuing high incidence of early acute myocardial infarction and an increasing operative mortality rate (7%) in the latest 3 years cohort of patients, excellent late survival and low subsequent cardiac event rates demonstrate the lasting effectiveness of prompt, successful emergency coronary bypass surgery for failed percutaneous coronary angioplasty.

Actuarial Analysis

Nosocomial urinary tract infections at a pediatric hospital.

Although the epidemiology of nosocomial urinary tract infections (NUTIs) is well-described in the adult population, there is little information on children. We therefore reviewed all our patients with NUTIs, to determine their age, underlying diagnoses, microorganisms involved, use of catheters and secondary bacteremias. During a 2-year period at our institution, NUTIs accounted for 10% of all nosocomial infections (0.8 infections/100 admissions). Of 44,948 patients admitted during this period 0.7% (n = 318) acquired 351 episodes of NUTI. The patient ages ranged from 5 days to 21 years. The highest rates of NUTIs per ward (NUTI/100 admissions or transfers to the ward) were seen in the neonatal surgery (4.8), hematology/oncology (2.7), infant neurosurgery (2.1) and neonatal intensive care units (1.9). The most common organisms isolated were Escherichia coli (26%), Enterococcus sp. (15%), Pseudomonas sp. (13%), Klebsiella sp. (10%) and coagulase-negative Staphylococcus (9%). Catheterrelated infections accounted for 48% of all the NUTIs. Secondary bacteremia occurred rarely, with an incidence of 2.9% (n = 7). We conclude that NUTIs represent an important proportion (10%) of nosocomial infections in our population of hospitalized children, but secondary bacteremia is uncommon.

Adolescent

Effect of an oxygen-enriched solution and multiple dosing of antegrade crystalloid cardioplegic solution on myocardial metabolism during coronary artery bypass graft operations.

The metabolic effect of excessive oxygenation and frequency of administration of antegrade crystalloid cardioplegic solution was assessed in 33 patients undergoing routine coronary artery bypass graft operations. Four patient groups were designed in which the initial aortic root injection was 1000 ml and then 100 ml administered through the vein grafts after completion of each distal anastomosis. The groups were divided as follows: group 1, single dose, normally oxygenated cardioplegic solution infused via the aortic root; group 2, single dose, high oxygen content cardioplegic solution infused via the aortic root; group 3, normally oxygenated cardioplegic solution with additional 250 ml doses via the aortic root every 20 minutes; group 4, high oxygen content cardioplegic solution with additional 250 ml doses via the aortic root every 20 minutes. In all groups myocardial mean septal temperature showed an immediate fall to approximately 11 degrees C with the initial aortic root doses and then a gradual rewarming to approximately 20 degrees C during the crossclamp period (mean 58.6 minutes). Metabolic parameters measured or calculated from the coronary sinus effluent were myocardial oxygen extraction, lactate production, base deficit, inorganic phosphate, glucose, potassium, creatine kinase (total and myocardial band fraction), and catecholamine production. There was no statistically significant difference in any of these determinations between each patient group. Furthermore, myocardial recovery, myocardial performance, and postoperative recovery characteristics were not different. We conclude that single or multidose aortic root crystalloid cardioplegic solution (either oxygen enriched or normally oxygenated) is equally effective in routine coronary artery bypass graft operations when septal temperatures are maintained between 15 degrees and 21 degrees C for a total arrest time of 60 minutes or less. In this study, increasing the volume cardioplegic solution given in multiple doses appeared to offer no significant metabolic or functional advantage in patients without complications who had satisfactory left ventricular function.

Cardioplegic Solutions

A sequential multi-assay protocol for the preclinical assessment of natural product complex carbohydrate immunomodulators.

A major barrier to the understanding, development and utilization of natural product complex carbohydrate immunomodulators has been the lack of standardization during pre-clinical efficacy and safety testing. In addition, it has been our experience that no single assay system or model is adequate for assessing preclinical efficacy and safety of these agents. To address these important issues, our laboratory group has developed a sequential multi-assay protocol for the preclinical evaluation of natural product complex carbohydrate immunomodulators. This sequential multi-assay screening protocol is divided into four phases: 1) physiochemical characterization of the carbohydrate polymer; 2) evaluation of immune stimulatory activity; 3) assessing in vivo anti-microbial activity and anti-tumor efficacy and 4) preclinical safety evaluation. This sequential protocol provides an effective, reproducible and rational approach to the preclinical assessment of complex carbohydrate immunomodulators that, in our experience, is predictive of clinical safety and efficacy.

Adjuvants, Immunologic

A method for the solubilization of a (1----3)-beta-D-glucan isolated from Saccharomyces cerevisiae.

This report describes a method for the solubilization of a micro-particulate beta-D-glucan. Insoluble glucan is dissolved in methyl sulfoxide and urea (8M) and partially phosphorylated at 100 degrees. The resulting water-soluble product is called glucan phosphate. The conversion rate is 70%, and the preparation is endotoxin free as determined by the Limulus lysate procedure. Glucan phosphate is composed of 34.66% C, 6.29% H, 42.83% O, and 2.23% P and has a repeating-unit empirical formula of (C6H10O5)7.PO3H2, indicating a phosphate group substitution on every seventh glucose subunit. Molecular-weight averages, polydispersity, and intrinsic viscosity were determined by aqueous high-performance size-exclusion chromatography (s.e.c.) with on-line, multi-angle laser light scattering (m.a.l.l.s.) photometry and differential viscometry (d.v.). Two polymer peaks were resolved. Peak 1 (Mw = 3.57 x 10(6) daltons), represents approximately 2% of the total polymers, while peak 2 (Mw = 1.10 x 10(5) daltons) comprises approximately 98% of polymers. 13C- and 31P-n.m.r. spectroscopy confirmed the beta-1,3 interchain linkage and the presence of a phosphate group. In solution, glucan phosphate polymers self-associate in a triple-helical arrangement. The ability to prepare a immunologically active, non-toxic, water-soluble beta-D-glucan preparation will greatly enhance the clinical utility of this class of compounds.

Drug Compounding

Late follow-up after repair of left ventricular aneurysm and (usually) associated coronary bypass grafting.

This study assesses clinical and operative data (LV) aneurysm was repaired to determine factors that might predict in-hospital and long-term outcome. Long-term follow-up study was obtained in 296 of 298 patients undergoing LV aneurysm repair with or without coronary artery bypass grafting between 1974 and 1986. No patient had sustained a myocardial infarction within 2 weeks of surgery or was undergoing other concurrent cardiac surgery. The average age of the study patients was 57 +/- 9 years and the average ejection fraction was 35 +/- 13%. Ninety percent of the patients underwent concurrent bypass grafting, with an average of 2.2 +/- 1.3 grafts placed. Fourteen (5%) patients died in the hospital, with most deaths attributable to LV dysfunction. Advanced age and less extensive revascularization were correlates of in-hospital mortality. The 10-year survival was 57%, myocardial infarction-free survival 43%, and freedom from death, myocardial infarction and reoperative coronary surgery 41%. Advanced age, systemic hypertension, significant left main coronary artery narrowing and emergent operative status were multivariate correlates of long-term mortality. A low-risk population was defined by the absence of these risk factors, and high-risk by the presence of greater than or equal to 1 risk factors. The 10-year survival was 71% in the low-risk and 41% in the high-risk groups (p = .0006). The 10-year myocardial infarction free survival was 55% in the low-risk and 31% in the high-risk groups (p = 0.0017). LV aneurysm repair may be performed with acceptable in-hospital mortality, and the long-term risk may be stratified.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

Multiple reoperative coronary artery bypass grafting.

Initial reoperative coronary artery bypass grafting is being performed commonly, and an increasing number of patients are being referred for subsequent reoperative coronary artery bypass grafting. From January 1980 through June 1990, 53 patients (52 male, 1 female) underwent a third or fourth coronary artery bypass operation and were retrospectively reviewed. This represented 0.3% (53/17,102) of the coronary artery bypass procedures done during that time period. The mean age was 59 +/- 8 years. The number of grafts placed ranged from one to four with an average of 2.6 per patient. Internal mammary artery grafts were used in 30 patients (57%). The mean left ventricular ejection fraction was 0.52 +/- 0.13. Intraaortic balloon pump support was necessary in 10 patients postoperatively. There were no intraoperative deaths, although 4 patients died in the postoperative hospitalization period. Perioperative myocardial infarctions were diagnosed in 6 patients, 13 patients had perioperative dysrhythmias, and 2 patients sustained a stroke. Superficial wound infections occurred in 5 patients. Late follow-up in 49 patients revealed that 2 other patients have since died, and no further myocardial infarctions have been reported in the survivors. Postoperative 3-year survival is 85%, whereas 3-year myocardial infarction-free survival is 70%. Although there is increased risk of operative complications and early death after multiple reoperative coronary artery bypass grafting, both in-hospital and long-term results suggest that it is an appropriate therapeutic strategy.

Coronary Artery Bypass

Preparation of the internal mammary artery for coronary bypass surgery.

Preparation of the internal mammary artery (IMA) for coronary bypass grafting is depicted. It is felt that this technique offers a simple, safe method for providing an IMA of maximum caliber and flow that allows not only end-to-side but sequential IMA grafting to a coronary artery. Use of this technique prepares the mammary artery to be used for both in situ and free grafting procedures to allow maximum utilization of the IMA as a superior conduit. The technique described has been used in several thousand operations.

Coronary Artery Bypass

Fatal rupture of an unsuspected post-traumatic aneurysm of the thoracic aorta during pregnancy.

A 27 year old woman presented during the third trimester of her second pregnancy complaining of chest pain. A chest radiograph showed a large aneurysm arising from the distal part of the aortic arch. She was transferred to the regional cardiothoracic centre but died suddenly on arrival. Necropsy confirmed a ruptured saccular aortic aneurysm arising just distal to the left subclavian artery. A history of a road traffic accident at the age of 12 was obtained from relatives after the patient's death. Vascular and haemodynamic changes in pregnancy may have caused the rupture of this previously silent post-traumatic aortic aneurysm.

Accidents, Traffic

Coronary bypass surgery: is the operation different today?

Patients undergoing coronary bypass grafting have undergone an evolution in recent years. To document this change, we analyzed two groups of patients in 1981 (n = 1586) and 1987 (n = 1513) to document preoperative and postoperative variables important in determining immediate morbidity and mortality after isolated coronary bypass. Between 1981 and 1987, patients were found to be older (greater than or equal to 70 years, 8.7% versus 21.8%, p less than 0.0001), more often diabetic (15% versus 24%, p less than 0.0001), have a greater prevalence of triple vessel disease (14.5% versus 46.1%, p less than 0.0001), and have more left ventricular dysfunction (ejection fraction 0.60 +/- 14 versus 0.54 +/- 13, p less than 0.0001). To facilitate analysis and because of overlap between subgroups, we subdivided patients into three subgroups for statistical comparison of the years 1981 and 1987: subgroup I, no prior procedure (n = 1546 in 1981 and 1396 in 1987); subgroup II, optimal group (n = 503 in 1981 and 292 in 1987, and defined as no prior procedure, ejection fraction greater than or equal to 0.50 and age less than 65 years); subgroup III, patients having reoperations (n = 40 in 1981 and 117 in 1987). Internal mammary artery grafting was infrequently used in 1981 but was used in 72.1% in 1987. Major postoperative morbidity between the 2 years for the total population increased significantly: need for intraaortic balloon pumping, 1.4% versus 4.7%, p less than 0.0001; myocardial infarction 3.5% versus 5.5%, p less than 0.008; stroke, 1.4% versus 2.8%, p less than 0.008; and wound infection, 1.0% versus 3.0%, p less than 0.001. Wound infection (all types) in 1987 was increased sevenfold in patients having a perioperative myocardial infarction (0.7% versus 5%, p less than 0.0001). For young patients with good left ventricular function (subgroup II), there was no increase in these morbid events between 1981 and 1987. Hospital mortality in the total population increased significantly between 1981 and 1987 from 1.2% to 3.1% (p less than 0.0002), respectively. It was lowest for the patients in optimal condition (subgroup II) in both years, 0.8% versus 1.1%, and highest for reoperative patients, 5.3% versus 4.3%. In 1981, 58% of patients (503/870) were in the optimal group compared with 35% (292/828) in 1987 (p less than 0.0001). The last six years have seen a progressive trend in surgically treating older, sicker patients who have more complex disease, with a significant reduction in the best candidate group.(ABSTRACT TRUNCATED AT 400 WORDS)

Age Factors

Isolation, physicochemical characterization and preclinical efficacy evaluation of soluble scleroglucan.

Herein we describe the isolation, physicochemical characterization and preclinical evaluation of a water-soluble biologic response modifier extracted from Sclerotium glucanicum. Alkaline extraction of insoluble S. glucanicum exopolymers produced a soluble scleroglucan composed of a triple-helical beta-1,3-linked glucopyranose backbone with single beta-1,6-linked glucopyranosyl branches every third subunit. Scleroglucan has a weight average molecular mass of 1.56 x 10(6) Da, a weight average root mean square distance from the center of gravity of the molecule to its farthest elements of 51.8 nm, a polydispersity (weight-average molecular mass/number average molecular mass) of 1.83 and intrinsic viscosity of 3.081 dl/g. Scleroglucan (250 mg/kg, intravenously) stimulated in vivo murine macrophage phagocytic activity (66%, P less than .001) and increased in vitro macrophage tumor cytotoxicity against syngeneic tumor targets by 124% (P less than .05). Scleroglucan enhanced (P less than .001) murine bone marrow proliferation in a biphasic manner by up to 328%. Scleroglucan therapy increased survival of mice challenged with syngeneic lymphoma, melanoma or adenocarcinoma. AKR/J mice bearing syngeneic lymphoma (1 x 10(3) cells, intraperitoneally) demonstrated increased (P less than .001) long-term survival (100% vs. 0%, greater than 64 days). C57Bl/6J mice bearing syngeneic melanoma B16 (5 x 10(5) cells, subcutaneously) demonstrated increased long-term survival (64% vs. 0%, P less than .05). C57Bl/6J mice bearing syngeneic adenocarcinoma BW10232 (1 x 10(5) cells, subcutaneously) demonstrated increased (P less than .05) median survival time. In addition, scleroglucan prophylaxis increased resistance of mice to challenge with Staphylococcus aureus, Candida albicans and mouse hepatitis virus A-59. Scleroglucan did not induce toxicity or hepatomegaly. We conclude that: 1) a branched, water-soluble beta-1,3-linked scleroglucan biologic response modifier can be extracted from S. glucanicum; 2) scleroglucan will stimulate immunity, modify experimental neoplastic disease and increase resistance to microbial challenge; and 3) scleroglucan shows promise as an immunopotentiating drug.

Animals

Influence of age on results of coronary artery surgery.

Coronary surgery is being used increasingly in older and more seriously ill patients. To evaluate the importance of age in predicting complications and mortality after coronary surgery, the results in 13,625 patients undergoing coronary surgery were evaluated. There were 321 patients under the age of 40, 1,758 were 40-49, 4,167 were 50-59, 5,049 were 60-69, 2,184 were 70-79, and 146 were over 80. As patients aged the proportion of women increased, the prevalence of severe angina and congestive heart failure increased, and the severity of the distributions of the coronary stenoses increased. The incidence of the complications of neurological events, wound infections, and death rose in every decade after the age of 40 years. The incidence of death was 0.6% for patients aged 40-49, 1.5% for those aged 50-59, 1.9% for those aged 60-69, 5.0% for those aged 70-79, and 8.3% for those aged 80-89. Advanced age was the most significant independent correlate of neurological events, wound infections, and death. The other multivariate correlates of neurological events were diabetes, hypertension, and, surprisingly, angina class. Again surprisingly, the only other multivariate correlate of wound infections was angina class. The other multivariate correlates of death were emergent surgery, female gender, ejection fraction, severity of coronary disease, diabetes, and a history of congestive heart failure. Of interest, periprocedural Q wave myocardial infarction was independent of age. The most predictive and significant correlate of periprocedural myocardial infarction was emergent surgery; hypertension, absence of a previous myocardial infarction, and a normal ejection fraction were weaker correlates. The ability to predict any complication was relatively weak compared with the ability to predict death. The relative infrequency of coronary surgery over the age of 80 years suggests that there is already strong selection against surgery in octogenarians. In addition, the risk of death, and to some extent other complications, may be predicted in advance based on extensive patient experience.

Adult