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Biomedical subjects

E L Jones

Publications and source records attributed to E L Jones.

At least 127 records · Page 7Linked to original sources

Primary malignant lymphoma of the large intestine complicating chronic inflammatory bowel disease.

Ten cases of malignant lymphoma of the colon and rectum complicating chronic inflammatory bowel disease are presented. Seven patients had chronic ulcerative colitis with a history varying from 6 to 20 years. There was extensive colitis in six of these patients and left-sided colitis in one. All seven lymphomas showed the pathological and immunohistological features of primary B-cell tumours of the gastrointestinal tract with a predominance of high-grade tumours. Three patients had Crohn's disease of the large intestine complicated by malignant lymphoma of the sigmoid colon or rectum. The history of Crohn's disease varied from 30 months to 20 years and in each case there was fissuring and fistulae. There was extensive anal involvement in two cases. Histologically the three lymphomas were heterogeneous: one was of 'granulomatous' T-cell type and the other two were markedly polymorphic and of equivocal phenotype. They were also characterized by numerous multinucleate tumour giant cells. Primary colorectal malignant lymphoma should be regarded as a rare, but significant, complication of ulcerative colitis. Immunosuppression may be an additional factor in the genesis of intestinal lymphoma in Crohn's disease. The prognosis appears to be dependent on factors already known to be of prognostic significance in primary gut lymphomas: a predominance of high-grade tumours suggests that the outlook is generally worse than that for idiopathic primary large intestinal lymphoma.

Adult↗

Determinants of prolonged length of hospital stay after coronary bypass surgery.

The length of hospital stay after coronary surgery was studied in 4,683 patients undergoing cardiac catheterization followed by coronary surgery at Emory University Hospital or Crawford Long Hospital between the years 1981 and 1986. Length of stay after coronary surgery had a median and modal value of 7 days. There was, however, a long statistical tail of patients with a prolonged length of stay extending out to more than 180 days. Prolonged length of stay (greater than 10 days) could be correlated with preprocedural variables such as age, elective versus emergency status, angina class, ejection fraction, and gender. Length of stay increased from a mean of 6.9 +/- 1.4 days under the age of 40 years to 10.9 +/- 12.1 days over the age of 70 years (p less than 0.0001). Length of stay was correlated with the periprocedural variables of wound infection, neurologic event, arrhythmias, pneumonia, postoperative myocardial infarction, mortality, and pericarditis. Length of stay increased from 8.8 +/- 9.6 days without a neurologic event to 21.1 +/- 17.9 days with a neurologic event (p less than 0.0001). Similarly, without a wound infection, the average stay was 8.7 +/- 8.9 days; with a wound infection, the average stay was 32.2 +/- 25.8 days (p less than 0.0001). The correlates of prolonged stay were tested in another population comprising 781 patients undergoing cardiac catheterization followed by coronary artery bypass grafting in 1987. The predictors of prolonged stay in the 1987 population were wound infection, pneumonia, arrhythmias, age, neurologic events, postoperative infarction, and ejection fraction. Thus, length of hospital stay after coronary surgery may be predicted by multiple preprocedural and periprocedural variables.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Coronary artery bypass surgery after failed elective percutaneous transluminal coronary angioplasty. A status report.

This study was performed to determine the procedural characteristics and in-hospital complications associated with failed percutaneous transluminal coronary angioplasty that necessitates coronary artery bypass graft surgery. The study population consisted of 316 patients from 1980 to 1986; 202 patients (64%) had emergency coronary artery bypass graft surgery and the remainder elective surgery during the same hospitalization. Mean age of the population was 56 +/- 9 years, 69% were male, and 69% had single-vessel disease. The failed percutaneous transluminal coronary angioplasty occurred most commonly on the first vessel attempted and was usually secondary to coronary artery dissection. Analysis of surgical technique revealed increased use of intra-aortic balloon pump in the emergency group (24% vs. 2% in the elective group, p less than 0.05). Overall, 2.0 +/- 1.0 (mean +/- SD) bypass grafts were placed, with increased use of the internal thoracic artery in the elective (32%) versus the emergency group (20%, p less than 0.05). A new, nonfatal, postprocedural Q-wave myocardial infarction occurred in 18% and developed more frequently in the emergency (27%) than in the elective (4%) cohorts. There were six in-hospital deaths (1.9%), an incidence which did not differ between groups. This analysis revealed a significant difference in operative technique between the emergency and the elective coronary artery bypass graft patients. Preoperative ischemia was significantly related to the development of the Q-wave myocardial infarction, yet not to in-hospital mortality.(ABSTRACT TRUNCATED AT 250 WORDS)

Angioplasty, Balloon↗

Catastrophic consequences of internal mammary artery hypoperfusion.

Inappropriate use of the internal mammary artery for complex coronary artery bypass operations may have disastrous yet avoidable consequences. In 712 consecutive coronary artery bypass operations performed between January 1985 and September 1986, five patients had an intraoperative course suggesting internal mammary artery hypoperfusion. In three, coronary artery bypass was performed as a reoperative procedure. The following similarities were noted in all five patients: a technically satisfactory internal mammary artery anastomosis, a left anterior descending coronary artery having critical proximal stenosis (greater than or equal to 90%), a distal artery at least 2.0 mm diameter free of disease, satisfactory left ventricular function, a catastrophic clinical outcome (death in three, cardiac transplantation in one, 3-month hospitalization in one), and all patients could be weaned from cardiopulmonary bypass only after insertion of a saphenous vein graft distal to the internal mammary artery graft. Bilateral internal mammary grafts were used in four of five patients. In both patients without prior coronary artery bypass, there was a discrepancy in internal mammary artery flow and myocardial demand: cardiac hypertrophy, large (2.5 mm) distal left anterior descending supplied by a small (less than 2.0 mm) internal mammary artery, and sequentially grafted arteries. All three patients having reoperative coronary artery bypass had normal anterior wall motion, and in two of the three patients, the left anterior descending-saphenous vein graft was arteriographically normal and the sole source of blood to the anterior, septum, and inferior myocardium. In two patients the normal left anterior descending-saphenous vein graft supply a large left anterior descending (greater than 2.0 mm) was replaced with a small left internal mammary artery. Internal mammary artery hypoperfusion typically occurred 30 to 40 minutes after discontinuation of cardiopulmonary bypass but was also seen in the intensive care unit. The condition may be confused with internal mammary artery or coronary artery spasm. It may be avoided by careful prebypass planning of the operation, intraoperative assessment of internal mammary artery flow and size with prudent use of sequential internal mammary artery grafting, avoiding use of the terminal left anterior descending (unless large), retaining nonobstructed saphenous vein grafts when the internal mammary artery has marginal flow or size, and placement of a saphenous vein graft distal to the left internal mammary artery when size or flow in the latter is small.

Aged↗

Response of a brachytherapy model using 125I in a murine tumor system.

The effects of low-dose-rate irradiation (brachytherapy) were investigated in vivo using a murine mammary adenocarcinoma (MTG-B) growing in the flank of C3H mice. For local tumor irradiations, a noninvasive cap was devised to cover the tumor and house three 125I seeds (average apparent activity 5.2 mCi each) located at 120 degree intervals around the circumference of the hemispherical cap (13 mm i.d.). Mice were secured during treatment in a tube allowing limited mobility while restricting access to the seeds. Tumors were exposed to a series of dose rates ranging from 14-40 cGy/h, and the total dose over the treatment interval (48 or 72 h) ranged from 830 to 2378 cGy. A total of nine experiments were conducted using the caps over a 10-week interval. In each experiment three groups (irradiated tumors, sham controls, and untreated controls) were analyzed, each containing 8-15 mice (N = 34, untreated control; N = 46, sham control; N = 91, brachytherapy irradiation). The brachytherapy results are compared to the effects of external beam irradiation in the same tumor system. A linear relationship was observed between the total radiation dose and doubling volume growth delay (GDDV) or treatment volume growth delay (GDTV) for the brachytherapy and external beam irradiation. The slopes of the dose-response curves are steeper for the acute dose (517 cGy/min) external beam irradiation (0.0072 day/cGy, GDDV; 0.00695 day/cGy, GDTV) than for the brachytherapy (0.0050 day/cGy, GDDV; 0.0057 day/cGy, GDTV) using both GDTV and GDDV end points. Comparison of the tumor volume regrowth slopes indicates that the tumor bed effect is larger for external beam irradiation than for brachytherapy, suggesting that the tumor bed effect may be dose-rate dependent.

Adenocarcinoma↗

A new approach to the treatment of advanced high-grade non-Hodgkin's lymphoma--intensive two-phase chemotherapy.

A total of 110 patients with high-grade non-Hodgkin's lymphoma (NHL) not previously treated by chemotherapy or by radiotherapy at more than one site of disease underwent a regimen comprising an intensive 6-week initial, induction phase using vincristine, adriamycin, methotrexate, and prednisolone (VAMP) followed by the non-cross-resistant combination cyclophosphamide, etoposide, and vindesine (EEE). The median age of patients was 54 years, the majority having stage IV disease. The median follow-up was 34 months and all patients have completed treatment. The overall complete remission (CR) rate for all patients was 68%. The initial phase of treatment produced a CR rate of 49%. The full regimen was completed by 87 patients, and of these, 66 (76%) achieved CR. Of those achieving CR, 72% were relapse-free, on an actuarial basis, at 2 years. Overall 2-year survival was 53%, with a median survival of 31 months. The survival of older patients and those with lymphoblastic histology was comparable to that of other groups. The survival prospects of patients with stage IV disease was not as good as that of other patients, with a significant trend to shorter survival in patients with more advanced disease. Toxicity was predictable and manageable for both phases of the regimen, although it was more severe for the initial phase. Dose-limiting toxicities were neutropenia and mucositis. This regimen is active in the treatment of advanced high-grade NHL with acceptable toxicity. These results have encouraged us to continue the study of weekly chemotherapy, which we will compare with standard cyclical chemotherapy in a prospective, randomized trial.

Adolescent↗

Effect of glucan on neutrophil dynamics and immune function in Escherichia coli peritonitis.

Previous studies from our laboratory have demonstrated that glucan, a nonspecific immunomodulator, modifies the course of murine Escherichia coli peritonitis. The protective effect of glucan was mediated, in part, by macrophages. In the present study, leukocyte dynamics in the peritoneal cavity and peripheral blood of glucan-treated mice following E. coli challenge was examined. Additional studies examined in vitro bone marrow proliferation, as well as phagocytosis and intracellular killing of E. coli by neutrophils following glucan administration. ICR/HSD mice were injected ip with glucan (150 mg/kg) or dextrose (5% w/v) on Days 5 and 3 prior to ip challenge with 1 X 10(8) E. coli. Glucan increased (P less than 0.05) total peritoneal neutrophil numbers prior to and following septic challenge. Examination of peripheral blood revealed that ip glucan treatment in E. coli peritonitis significantly (P less than 0.001) increased the number of circulating neutrophils. Additionally, neutrophils from glucan-treated mice showed increased phagocytosis of E. coli in vitro. Glucan therapy also increased bone marrow proliferation. We conclude that (1) glucan enhances peritoneal neutrophil levels, (2) peripheral blood neutrophils are increased following glucan and E. coli, (3) ip glucan increases bone marrow proliferation, and (4) neutrophils from glucan-treated mice showed enhanced phagocytosis of E. coli in vitro. Thus, the beneficial effect of glucan is mediated not only by activated macrophages, but also by the neutrophilic leukocyte.

Animals↗

Pre-clinical safety evaluation of soluble glucan.

Soluble glucan, a beta-1,3-linked glucopyranose biological response modifier, is effective in the therapy of experimental neoplasia, infectious diseases and immune suppression. Currently, soluble glucan is undergoing phase I clinical trials. The present study describes the pre-clinical safety evaluation of soluble glucan in mice, rats, guinea pigs and rabbits. ICR/HSD mice and Harlan Sprague-Dawley rats received a single i.v. injection of soluble glucan in doses ranging from 40 to 1000 mg/kg. Soluble glucan administration did not induce mortality, appearance or behavioral changes in mice or rats. In subsequent studies, mice and guinea pigs were injected i.p. with glucan (250 mg/kg) for 7 consecutive days. ICR/HSD mice gained weight at the same rate as the saline-treated controls. In contrast, guinea pigs receiving i.p. injections of soluble glucan showed a significant (P less than 0.05) 10-13% decrease in weight gain over the 7 day period. No other toxicologic, behavioral or appearance changes were noted. To examine chronic toxicity, soluble glucan was administered twice weekly for a period of 30 or 60 days to ICR/HSD mice in the dose of 40, 200 or 1000 mg/kg. No deaths were observed in any group. Chronic glucan administration did not alter body weight, liver, lung or kidney weight. However, a significant splenomegaly was observed in both the 30 and 60 day study. Histopathologic examination showed no tissue alterations at 40 or 200 mg/kg. However, at 1000 mg/kg a mononuclear infiltrate was observed in the liver. Pyrogenicity testing, employing New Zealand white rabbits, revealed that parenteral glucan administration (5 mg/kg) did not significantly alter body temperature. These data indicate that the systemic administration of soluble glucan, over a wide dose range, does not induce mortality or significant toxicity, an important consideration in preparing soluble glucan for parenteral administration to human populations.

Animals↗

Aortic and mitral valve replacement in idiopathic hypereosinophilic syndrome.

Idiopathic hypereosinophilic syndrome is a rare systemic manifestation of eosinophilia that may cause endocardial fibrosis. Endocardial fibrosis and overlying thrombus typically lead to a restrictive cardiomyopathy and heart failure. Occasionally mitral or tricuspid regurgitation (or both) occurs as a result of the fibrosis and thrombus formation. This report describes a patient with hypereosinophilic syndrome who was seen with an unusually localized form of cardiac involvement that resulted in predominantly aortic and mitral stenosis. This was treated with bivalvular replacement.

Adult↗

Trends in invasive treatment of single-vessel and double-vessel coronary disease.

We examined our practice of invasive therapy for one- and two-vessel coronary disease to assess the impact of the randomized trials of coronary surgery and the current use of angioplasty. We first reviewed our results with coronary artery bypass graft in equivalent patients in the Coronary Artery Surgery Study with one- and two-vessel disease between 1976 and 1981. Among 1376 patients, hospital mortality was 0.07%, and 5-year survival was 95.2% +/- 0.8%. To define trends in invasive therapy, which have since occurred, we compared 100 patients with one- and two-vessel disease in each of three groups: 1979 coronary artery bypass graft, 1984 coronary artery bypass graft, and 1984 percutaneous transluminal coronary angioplasty. Preoperative characteristics in the average 1979 and 1984 patients were similar; however, in 1984, patients who had a coronary artery bypass graft were older than patients who had percutaneous transluminal coronary angioplasty (61.5 versus 56.7 years, p less than 0.01), they required more heart medications (2.1 versus 1.5, p less than 0.01), had more previous infarctions (0.8 versus 0.5, p less than 0.01), and more patients had an ejection fraction of less than 50% (34% versus 7%, p less than 0.01). Patients who had angioplasty had a shorter postoperative stay (median number of days 7, 7, 2, p less than 0.01). Freedom from major complications was similar among the groups (91%, 87%, 85%). Unstable symptoms were the most frequent indication for invasive therapy (approximately 80%), whereas long-term symptoms, those considered in the randomized trials, occurred in relatively few patients. The number of patients without at least one definite indication for invasive therapy was 13%, 3%, and 11%, p less than 0.05, suggesting that the indications for the 1984 coronary artery bypass graft group have become more restrictive since the 1979 coronary artery bypass graft group. Indications for the 1984 percutaneous transluminal coronary angioplasty group remained less restrictive, being similar to those for the 1979 coronary artery bypass graft group. A continuing trend toward the use of percutaneous transluminal coronary angioplasty was evident, as 56% of the 1979 coronary artery bypass graft group of patients and 32% of the 1984 coronary bypass group of patients would be offered percutaneous transluminal coronary angioplasty rather than coronary artery bypass graft on the basis of 1986 percutaneous transluminal coronary angioplasty criteria. The p values were obtained with analysis of variance or chi 2 test.

Angioplasty, Balloon↗

The role of complement in glucan-induced protection against septic shock.

Previous studies from our laboratory have shown that glucan will significantly enhance survival, decrease bacteremia, maintain reticuloendothelial function, and reduce histopathology in a murine model of gram-negative septic shock [1]. The present study was undertaken to evaluate the role of complement in glucan-enhanced protection against septic shock. AKR/J mice, which are congenitally C5-deficient, and ICR/HSD mice that were complement-depleted by treatment with purified cobra venom factor (CVF), were injected IP with glucan (50 mg/kg) on days 5 and 3 prior to IP challenge with 1 X 10(8) E. coli. Survival data indicated that glucan (p less than 0.05) increased survival in both C5-deficient and complement-depleted mice. Glucan prophylaxis resulted in a neutrophilic leukocytosis 8 h following E. coli challenge. However, glucan did not alter bone marrow proliferation. We conclude that, 1) glucan's protective effect on survival is not dependent on complement, 2) complement is not required for glucan-induced neutrophilic leukocytosis in this model, and 3) glucan does not enhance bone marrow proliferation in complement-deficient mice.

Animals↗

Treatment of moderate mitral regurgitation and coronary disease by coronary bypass alone.

We have favored treatment of moderate mitral regurgitation and coronary disease with coronary bypass alone because of the high operative mortality of combined mitral valve replacement and coronary bypass. Between 1977 and 1983, coronary bypass alone was performed on 58 patients (mean age 63 +/- 8 years). Preoperatively, 90% had Canadian Cardiovascular Society class III or IV angina, and 10% had class III or IV congestive heart failure. In 72% mitral regurgitation had been caused by coronary disease. Hospital mortality was 3.4% (2/58). At follow-up (100% complete, mean 4.3 years) 66% of survivors were functional classes I and II (compared with 7% preoperatively, p less than 0.0001). Of those patients who worked preoperatively, 84% returned to work. There were no reoperations. The 5-year survival was 77%. In the same period combined mitral valve replacement and coronary bypass was required in 20 unmatched patients with moderate mitral regurgitation and coronary disease. Indications for valve replacement included congestive heart failure (10 cases), high left atrial pressure (three cases), and mitral stenosis (four cases). In these patients with more advanced symptoms the hospital mortality was 25%, and the 5-year survival was 31%. Treatment of moderate mitral regurgitation and coronary disease by coronary bypass alone achieved excellent hospital survival and long-term functional stability without a subsequent valve operation.

Aged↗

Predictors of mortality, complications, and length of stay in aortic valve replacement for aortic stenosis.

The introduction of aortic balloon valvuloplasty has prompted review of established techniques to treat aortic valve disease. To this end, the surgical results were reviewed for 1,148 patients undergoing aortic valve replacement, with and without associated coronary artery bypass grafting, for aortic stenosis between January 1, 1975 and September 1, 1987. The overall death rate was 4.6%. The neurological event rate (stroke or reversible ischemic event) was 4.2%, the myocardial infarction rate was 3.5%, and 30.7% had a hospital stay in excess of 10 days. Mortality for isolated elective aortic valve replacement rose from 2.5% for patients under age 70 to 7.3% for those over age 70. Mortality for elective aortic valve replacement plus coronary bypass was 3.8% for patients under age 70 and 11.6% for patients over age 70. The neurological event rate rose from 3.0% to 8.4% and the prolonged length of stay from 28% to 42%. By stepwise logistic regression analysis, the predictors of in-hospital mortality were age and emergent surgery. Age was the only multivariate predictor of neurological events. The year of surgery and emergent status were the multivariate predictors of prolonged length of hospital stay. Aortic valve replacement for aortic stenosis is a well-established technique with low neurological event rates and mortality, which may be predicted in advance. Newer techniques must be considered in light of data such as these.

Aged↗

Soluble glucan and lymphokine-activated killer (LAK) cells in the therapy of experimental hepatic metastases.

Previous studies have indicated the efficacy of adoptive immunotherapy utilizing recombinant interleukin-2 (rIL-2) and lymphokine-activated killer (LAK) cells in the treatment of advanced neoplastic disease. However, this therapeutic approach is associated with considerable toxicity, primarily due to the systemic administration of rIL-2. The present study was undertaken to determine the efficacy of a newly developed water-soluble glucan, when administered in combination with LAK cells, in the therapy of experimental hepatic metastases. Mice were challenged subcutaneously (1 X 10(4) cells) with reticulum cell sarcoma M5076 on day 0. Therapy was initiated on day 15, when a palpable primary tumor mass and hepatic micrometastases were evident, and continued at 3-day intervals up to day 54. Sarcoma-bearing mice received glucan (250 mg/kg) intravenously, either alone or in combination with LAK cells (1 X 10(7)/mouse). Control mice received 5% (wt/vol) dextrose in water. Glucan-LAK cell therapy significantly suppressed primary tumor growth, inhibited the progression of hepatic metastases and prolonged survival in sarcoma-bearing mice. Splenocytes, incubated with rIL-2 for 72 h, exhibited significant natural killer (NK) cell activity and were cytotoxic to sarcoma cells in vitro. Glucan-LAK cell administration resulted in significant increases in splenic NK cell activity and Kupffer cell-mediated tumoricidal activity. In addition, bone marrow proliferation was enhanced following the co-administration of glucan and LAK cells. Due to its nontoxic nature and immunostimulating properties, soluble glucan may prove to be an attractive biological response modifying agent for utilization in adoptive immunotherapy of advanced neoplastic disease.

Animals↗

In vitro tumoricidal activity of resting and glucan-activated Kupffer cells.

Kupffer cells compose 80-90% of fixed tissue macrophages and have been suggested to play an important role in hepatic antitumor resistance. In the present study, the ability of resting and activated Kupffer cells to lyse syngeneic mammary adenocarcinoma BW10232 cells was evaluated. Activated Kupffer cells were isolated from C57Bl/6J mice following single of multiple intravenous (IV) injections of glucan (0.45 mg/mouse), a potent macrophage-activating agent. Mice receiving 5% (w/v) dextrose served as control. Resting Kupffer cells induced significant (P less than .05) 4% and 12% specific lysis of adenocarcinoma cells at target:effector ratios of 1:10 and 1:50, respectively. Kupffer-cell-mediated tumoricidal activity was depressed on day 1 following a single IV injection of glucan. By day 3 postglucan, the antitumor activity of Kupffer cells returned to control levels and was enhanced on days 5 and 10. Following multiple IV injections of glucan on days -5, -3, and -1, Kupffer-cell-mediated cytotoxicity was elevated on days 1 and 4. These observations demonstrate that resting Kupffer cells are significantly cytotoxic to adenocarcinoma cells at T:E ratios of 1:10 and 1:50 and following a transient inhibition of Kupffer-cell-mediated tumoricidal activity, glucan was effective in significantly enhancing the antitumor activity of Kupffer cells.

Adenocarcinoma↗