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Biomedical subjects

C L Nelson

Publications and source records attributed to C L Nelson.

At least 37 records · Page 2Linked to original sources

Age-dependent neurobehavioral plasticity following forebrain dopamine depletions.

The differential neurobehavioral effects of forebrain dopamine (DA) depletions in neonatal and adult rats are reviewed. In contrast to the severe and long-lasting parkinsonian sensorimotor deficits seen in rats sustaining large DA depletions as adults, rats comparably depleted as neonates are spared from these gross behavioral deficits. While DA released from residual striatal DA terminals remains necessary for the gradual recovery of sensorimotor function in rats lesioned as adults and the sparing from deficits in rats lesioned as neonates, the specific roles of D1- and D2-like receptors differ between the two age groups. Coactivation of striatal D1 and D2 receptors by residual DA is necessary for the expression of sensorimotor behavior in rats depleted of DA as adults (and in intact rats) whereas activation of either D1 or D2 receptors is sufficient for these behaviors in rats depleted of DA as neonates. We discuss the D1/D2 modulation of several important markers for striatal transmission (acetylcholine release from interneurons, induction of c-fos, and the expression of GAD65 mRNA in striatal efferents) as potential mechanisms underlying this striking age-dependent plasticity following forebrain DA depletions.

Aging↗

Visualization of bacterial glycocalyx with a scanning electron microscope.

Using a new technique for scanning electron microscopic preparation, bacterial glycocalyx is seen in its natural, highly hydrated state for the first time. Visual images of the glycocalyx obtained from these preparations are a marked departure from the visual images of glycocalyx obtained previously with conventional scanning electron microscopic analysis. The dominating presence of glycocalyx visualized in its naturally hydrated state gives credence to the role of bacterial glycocalyx as a mechanical barrier to host defenses and antibiotics and supports the role of glycocalyx as a significant factor in bacterial virulence.

Animals↗

Relationship between diabetes mellitus and long-term survival after coronary bypass and angioplasty.

BACKGROUND: Recent subgroup analyses of randomized trials have suggested that percutaneous intervention in diabetic patients with multivessel disease results in higher mortality than coronary artery bypass graft surgery (CABG). We studied the relationship between diabetes and survival after revascularization in a large prospective cohort of patients with multivessel coronary artery disease. METHODS AND RESULTS: By analyzing data for 3220 patients (24% diabetic) with symptomatic two- or three-vessel coronary disease who were undergoing percutaneous transluminal coronary angioplasty (PTCA) or CABG at Duke University Medical Center between 1984 and 1990, we found that at 5 years, unadjusted survival in the group of patients undergoing CABG was 74% in diabetics and 86% in nondiabetics. Similarly, 5-year survival among PTCA patients was 76% in diabetics and 88% in patients without diabetes. After adjustment for baseline characteristics, diabetic patients receiving either PTCA or CABG had significantly poorer survival than nondiabetics (chi2=43.56, P<.0001). Unlike previous studies, however, there was no significant differential effect of diabetes on outcome between patients treated with PTCA and those treated with CABG (chi2=0.01, P=.91). CONCLUSIONS: Although diabetes was associated with a worse long-term outcome after both PTCA and CABG in patients with multivessel coronary artery disease, the effect of diabetes on prognosis was similar in both treatment groups. Thus, our findings support the concept that the choice of initial revascularization strategy should not be based exclusively on a history of diabetes but rather should rely on other factors, such as angiographic suitability and clinical status.

Aged↗

Relationship between physician and hospital coronary angioplasty volume and outcome in elderly patients.

BACKGROUND: With the expectation that physicians who perform larger numbers of coronary angioplasty procedures will have better outcomes, the American College of Cardiology/ American Heart Association guidelines recommend minimum physician volumes of 75 procedures per year. However, there is little empirical data to support this recommendation. METHODS AND RESULTS: We examined in-hospital bypass surgery and death after angioplasty according to 1992 physician and hospital Medicare procedure volume. In 1992, 6115 physicians performed angioplasty on 97,478 Medicare patients at 984 hospitals. The median numbers of procedures performed per physician and per hospital were 13 (interquartile range, 5 to 25) and 98 (interquartile range, 40 to 181), respectively. With the assumption that Medicare patients composed one half to one third of all patients undergoing angioplasty, these median values are consistent with an overall physician volume of 26 to 39 cases per year and an overall hospital volume of 196 to 294 cases per year. After adjusting for age, sex, race, acute myocardial infarction, and comorbidity, low-volume physicians were associated with higher rates of bypass surgery (P < .001) and low-volume hospitals were associated with higher rates of bypass surgery and death (P < .001). Improving outcomes were seen up to threshold values of 75 Medicare cases per physician and 200 Medicare cases per hospital. CONCLUSIONS: More than 50% of physicians and 25% of hospitals performing coronary angioplasty in 1992 were unlikely to have met the minimum volume guidelines first published in 1988, and these patients had worse outcomes. While more recent data are required to determine whether the same relationships persist after the introduction of newer technologies, this study suggests that adherence to minimum volume standards by physicians and hospitals will lead to better outcomes for elderly patients undergoing coronary angioplasty.

Age Factors↗

Treatment of experimental osteomyelitis by surgical debridement and the implantation of bioerodable, polyanhydride-gentamicin beads.

Osteomyelitis was induced in the radius in 77 rabbits and confirmed by histological examination and culture. At 4 weeks, the wounds were debrided and the animals were treated with (a) fatty acid dimer-sebacic acid beads (a bioerodable composite) impregnated with 20% or (b) 10% gentamicin sulfate, (c) placebo beads and intramuscular gentamicin sulfate, (d) placebo beads alone, or (e) debridement only. After 4 weeks, eradication of infection was determined by histological examination and culture. Osteomyelitis was eradicated in 93% of the animals treated with the beads and 20% gentamicin, in 67% of those treated with the beads and 10% gentamicin, in 25% of those treated with placebo beads and intramuscular gentamicin, in 7% of those treated with placebo beads alone, and in 12.5% of those treated with debridement only (p values from < 0.001 to 0.02). Fatty acid dimer-sebacic acid beads with gentamicin were then implanted in noninfected rabbits, and gentamicin sulfate concentrations in bone, serum, urine, and wound exudate were measured. Gentamicin sulfate was detectable in bone for as long as 8 weeks after implantation. Levels as high as 4,746 micrograms/ml were present in the wound exudate for the first 7 days. Levels in the serum peaked at 1.03 micrograms/ml. Urine levels peaked at 135 micrograms/ml.

Anhydrides↗

Characterization of a rabbit model of staphylococcal osteomyelitis.

We previously described a rabbit osteomyelitis model that involved the direct introduction of Staphylococcus aureus into devascularized bone. To further evaluate the model, we performed experiments aimed at correlating the microbiological, radiographic, and histologic parameters involved in the development of experimental osteomyelitis. Using the strain UAMS-1, we achieved an infection rate of 75% with an inoculum as small as 2 x 10(3) colony-forming units. However, development of significant radiographic and histologic signs of disease required an inoculum of at least 2 x 10(4) colony-forming units. Radiographic signs were minimal 1 week after infection and progressed steadily to a maximum 3 weeks after infection. In contrast, histologic signs of disease were observed within 1 week and remained essentially unchanged throughout the 4-week evaluation period. Unlike the results obtained with UAMS-1, rabbits infected with the heavily encapsulated Staphylococcus aureus strain Smith diffuse exhibited little evidence of disease even when infected with 2 x 10(6) colony-forming units. The reduced virulence of strain Smith diffuse was surprising given its greatly enhanced virulence (relative to UAMS-1) in a murine peritonitis model of staphylococcal disease. These results suggest that UAMS-1 expresses virulence factors that are important in the pathogenesis of osteomyelitis and that some or all of these virulence factors are either absent or are not expressed in strain Smith diffuse. Most importantly, the results suggest that our model may be appropriate for the identification and characterization of these virulence factors.

Animals↗

The natural history of single-vessel chronic coronary occlusion: a 25-year experience.

To determine the natural history of patients with a total occlusion of a single coronary artery, we searched the Duke Databank for Cardiovascular Disease to find all patients who underwent a first coronary angiogram >2 days after a symptomatic myocardial infarction between 1969 and 1994. Patients who underwent angiography >30 days after the acute event had a low risk of death in the first year (3%), and a proximal left anterior descending coronary occlusion did not confer substantially higher risk of death (4%). Patients undergoing angiography <30 days after the acute event had a higher mortality (5%), especially those with proximal left anterior descending occlusion (10%). The time from the acute event to angiography was a predictor of death (p = 0.04). Despite low 1-year mortality rates, patients with total occlusion of an isolated coronary vessel treated medically had substantial mortality, myocardial infarction, and revascularization rates over a long-term follow-up period.

Adult↗

Resurfacing of only the femoral head for osteonecrosis. Long-term follow-up study.

Fourteen patients (21 hips) with osteonecrosis of the femoral head with collapse had the femoral head resurfaced with a cemented titanium shell. All of the femoral heads were Ficat stage III or IV. Of the 21 surgeries, 7 were failures. Treatment for all 4 patients with sickle cell disease or trait failed (100%). When the cases of 17 patients who did not have sickle cell disease or trait were reviewed separately, the success rate was 14 of 17 (82%). The follow-up periods (all > 5 years) of the 14 successful patients in this group averaged 6.2 years, and their average Harris hip score was 87 (10 excellent, 4 good). Of the 14 successes, 10 patients had a follow-up period longer than 5 years (average, 7.7 years) and an average Harris hip score of 94 (7 excellent, and 3 good). There was no evidence of loosening and there was no osteolysis. It is concluded that this operation provides an alternative to hemiarthroplasty, total joint arthroplasty surgery, or bipolar arthroplasty. This is a time-buying first-stage operation and, for younger patients, will not last a lifetime. The concept appears prudent because the surgical procedure is directed at the site of primary disease, the femoral head.

Adolescent↗

Relation between activated clotting time during angioplasty and abrupt closure.

BACKGROUND: The purpose of this study was to determine whether the degree of heparin anticoagulation during coronary angioplasty, as measured by the activated clotting time, is related to the risk of abrupt vessel closure. METHODS AND RESULTS: Sixty-two cases of in- and out-of-laboratory abrupt closure in patients in whom intraprocedure activated clotting times were measured were identified from a population of 1290 consecutive patients who underwent non-emergency coronary angioplasty. This group was compared with a matched control population of 124 patients who did not experience abrupt closure. Relative to the control population, patients who experienced abrupt closure had significantly lower initial (median, 350 seconds [25th to 75th percentile, 309 to 401 seconds] versus 380 seconds [335 to 423 seconds], P = .004) and minimum (345 seconds [287 to 387 seconds] versus 370 seconds [321 to 417 seconds], P = .014) activated clotting times. Higher activated clotting times were not associated with an increased likelihood of major bleeding complications. Within this population, a strong inverse linear relation existed between the activated clotting time and the probability of abrupt closure. CONCLUSIONS: This study demonstrates a significant inverse relation between the degree of anticoagulation during angioplasty and the risk of abrupt closure. A minimum target activated clotting time could not be identified; rather, the higher the intensity of anticoagulation, the lower the risk of abrupt closure.

Aged↗

Long-term survival benefits of coronary artery bypass grafting and percutaneous transluminal angioplasty in patients with coronary artery disease.

The purpose of this study was to evaluate long-term survival benefits of bypass surgery and angioplasty versus medical therapy in 9263 patients at Duke University Medical Center between 1984 and 1990 with coronary artery disease confirmed by cardiac catheterization to involve one, two, or three vessels. Clinical data were prospectively entered into an established cardiovascular database, and annual follow-up was 97% complete for a mean interval of 5.3 years and a maximal interval of 10 years. Outcomes were analyzed with the Coronary Artery Surgery Study "method A" to define patient groups treated by medicine (n = 2449), angioplasty (n = 2924), or bypass surgery (n = 3890). Differences among treatment groups in baseline characteristics were adjusted by Cox proportional hazard models. The anatomic severity of coronary artery stenosis best defined survival benefit from bypass surgery and angioplasty versus medical treatment. One or both interventional treatments provided better long-term survival than did medical treatment for all levels of disease severity. All patients with single-vessel disease, except those with at least 95% proximal left anterior descending stenosis, benefited from angioplasty versus bypass. All patients with three-vessel disease and those two-vessel patients with > or = 95% proximal left anterior descending stenosis benefited from bypass surgery versus angioplasty. All other patients with two-vessel disease and those with > or = 95% proximal left anterior descending stenosis only had similar survival with either interventional treatment. The absolute survival benefit was greatest for patients with severe three-vessel disease treated with bypass surgery.

Angioplasty, Balloon, Coronary↗

The change in serum protein concentration in response to the stress of total joint surgery: a comparison of older versus younger patients.

OBJECTIVE: To investigate whether the physiological response to surgery-induced stress, as measured by changes in serum secretory proteins, is more profound on older than in younger total joint arthroplasty patients. DESIGN: Retrospective study. SETTING: A 267-bed teaching hospital. PARTICIPANTS: A total of 220 ambulatory patients with normal admission serum albumin levels, of whom 106 were 65 years of age or older (mean age 73.3 +/- 6.2 years) and 114 less than age 65 (mean age 48.8 +/- 12.2 years). METHODS: Serum albumin and transferrin levels obtained at admission an on the fifth and tenth postoperative days were compared in the two age groups. RESULTS: In both age groups, admission serum albumins were significantly higher than on the corresponding postoperative Day 5 levels (40.4 +/- 3.7 g/L vs 25.0 +/- 3.3 g/L, P < .0001 and 39.5 +/- 2.5 g/L vs 23.9 +/- 3.1 g/L, P < .001 in older and younger patients, respectively). The drop in the serum concentration of albumin by postoperative Day 5 in the older patients was not significantly different from that of the younger patients (a drop of 15.6 +/- 3.3 g/L in older vs 15.4 +/- 4.4 g/L for the younger, P = .740). Among the 64 patients who remained in the hospital 10 days subsequent to surgery, the average postoperative Day 10 serum albumin concentration was significantly lower in the older patients when compared with the younger (26.2 vs 29.1 g/L P = .016). Similar results were obtained for serum transferrin. CONCLUSIONS: Subsequent to elective arthroplasty, the magnitude of change in serum albumin and transferrin concentrations is similar in older compared with younger, patients, suggesting that this stress response to surgery is nor age dependent. In contrast, the rate of recovery of the serum protein concentrations to preoperative levels may be slower in the older patients. However, this issue needs to be investigated further.

Adolescent↗

Effect of delayed admission to the hospital on the preoperative prevalence of deep-vein thrombosis associated with fractures about the hip.

Thirteen (10 per cent) of 133 patients who had venography on admission to the hospital for a fracture about the hip had radiographic evidence of deep-vein thrombosis. Only seven (6 per cent) of the 122 patients who were seen at the hospital within two days after the fracture had evidence of thrombosis. However, six of the eleven patients who had a delay of more than two days between the fracture and admission to the hospital had evidence of thrombosis. Although there was no significant difference between these two groups with respect to the mean age, sex distribution, frequency of fracture type, or history of deep-vein thrombosis, there was a significant difference in the prevalence of thrombosis in the patients who had a delay before admission to the hospital compared with those who did not (p<0.001). These results suggest that there is a substantial risk of venous thromboembolic disease in patients who have a fracture about the hip, regardless of whether or not they have had an operation, and that this risk increases if the time to presentation is delayed. Consequently, patients for whom there was a delay between a fracture about the hip and admission to the hospital should be considered to be at high risk for, and should be evaluated for, deep-vein thrombosis preoperatively.

Age Factors↗

The use of erythropoietin in the management of Jehovah's Witnesses who have revision total hip arthroplasty.

Five Jehovah's Witnesses (one man and four women) were managed with revision total hip arthroplasty. The average age of the patients at the time of the index operation was 66.4 years (range, fifty-eight to seventy-eight years). All of the patients received subcutaneous injections of recombinant human erythropoietin before the operation, at an initial dose of 100 international units per kilogram of body weight three times a week. The duration of preoperative treatment was determined by the hematocrit at the time of presentation. The hematocrit was monitored weekly, beginning with the second week of treatment, and the dose was adjusted accordingly until the time of the operation. Erythropoietin therapy was discontinued if the hematocrit exceeded 0.45 at any time. The hematocrit before the erythropoietin therapy was begun, at the time of admission to the hospital (one or two days preoperatively), immediately postoperatively, and at the time that the patient was discharged were recorded for this study. All five revision total hip arthroplasties were performed successfully without a blood transfusion. No patient had any complications associated with an excessive loss of blood or a low hematocrit. The average hematocrit was 0.395 (range, 0.317 to 0.447) before the erythropoietin therapy was begun and was 0.476 (range, 0.431 to 0.509) after treatment with erythropoietin and before the operation (that is, at the time of admission to the hospital). The average duration of erythropoietin therapy was twenty-six days preoperatively and 3.6 days postoperatively. The average hematocrit was 0.368 (range, 0.272 to 0.424) immediately after the operation and was 0.308 (range, 0.294 to 0.327) at the time of discharge from the hospital. No patient had evidence of deep venous thrombosis. This study illustrates that it is possible and apparently safe to optimize the hematocrit, by use of erythropoietin, in a patient who is scheduled for an operation. This may be particularly beneficial to a patient with anemia who has failure of a total hip arthroplasty. A relatively high hematocrit (0.45 to 0.50) preoperatively provides a relative margin of safety to a procedure that frequently involves a great deal of intraoperative blood loss. The use of erythropoietin preoperatively is particularly suited to joint replacements and revisions because of their elective nature and the moderately flexible timing associated with these procedures.

Aged↗

Association of body mass index and body fat distribution with risk of lung cancer in older women.

Obesity has been associated with an increased risk of cancer at a number of sites. A notable exception appears to be lung cancer, for which several studies suggest a modest inverse association. However, cigarette smoking is directly associated with lung cancer and inversely associated with body mass index. To investigate the hypothesis that body mass index is associated with lung cancer independent of cigarette smoking, the authors analyzed data from a prospective cohort study of 41,837 Iowa women aged 55-69 years at baseline in 1986. In addition, they examined whether central adiposity (high waist/hip ratio) was associated with lung cancer incidence. Through 1992 (6 years of follow-up), 233 cases of lung cancer were identified through the State Health Registry of Iowa. The body mass index at several ages was calculated from self-reports of height at baseline and weights at ages 18, 30, 40, and 50 years and at baseline. Current and former smokers generally had lower mean body mass indices than did nonsmokers at all ages except 18 years. Cases generally had lower body mass indices than did noncases at all ages except 18 and 30 years but, among current smokers, cases had higher mean body mass indices than did noncases at all ages except baseline, although the differences were not statistically significant. An apparent positive association of a high waist/hip ratio with lung cancer in the total cohort was found to be primarily accounted for by a higher waist/hip ratio in current and former smokers. When stratified by smoking status and adjusted for other risk factors, including age and pack-years of smoking, the body mass index at baseline, body mass index at age 50 years, and waist/hip ratio were not associated with lung cancer. The results of multivariate analyses suggest that the inverse association of body mass index with lung cancer can be explained by smoking status and that the positive association of waist/hip ratio with lung cancer can be explained by pack-years of smoking.

Age Distribution↗

Cost effectiveness of thrombolytic therapy with tissue plasminogen activator as compared with streptokinase for acute myocardial infarction.

BACKGROUND: Patients with acute myocardial infarction who were treated with accelerated tissue plasminogen activator (t-PA) (given over a period of 1 1/2 hours rather than the conventional 3 hours, and with two thirds of the dose given in the first 30 minutes) had a 30-day mortality that was 15 percent lower than that of patients treated with streptokinase in the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO) study. This was equivalent to an absolute decrease of 1 percent in 30-day mortality. We sought to assess whether the use of t-PA, as compared with streptokinase, is cost effective. METHODS: Our primary, or base-case, analysis of cost effectiveness used data from the GUSTO study and life expectancy projected on the basis of the records of survivors of myocardial infarction in the Duke Cardiovascular Disease Database. In the primary analysis, we assumed that there were no additional treatment costs due to the use of t-PA after the first year and that the comparative survival benefit of t-PA was still evident one year after enrollment. RESULTS: One year after enrollment, patients who received t-PA had both higher costs ($2,845) and a higher survival rate (an increase of 1.1 percent, or 11 per 1000 patients treated) than streptokinase-treated patients. On the basis of the projected life expectancy of each treatment group, the incremental cost-effectiveness ratio--with both future costs and benefits discounted at 5 percent per year--was $32,678 per year of life saved. The use of t-PA was least cost effective in younger patients and most cost effective in older patients. At all ages, the use of t-PA in patients with anterior infarctions yielded more favorable cost-effectiveness values. In our secondary analyses, the cost-effectiveness values were most sensitive to a lowering of the projected long-term survival benefits of t-PA and to moderate or greater increases in the projected medical costs for patients in the t-PA group after the first year. In contrast, our results were not sensitive to even very unfavorable assumptions about the additional costs associated with the higher rate of disabling stroke that was noted in patients treated with t-PA in the GUSTO study. CONCLUSIONS: The cost effectiveness of treatment with accelerated t-PA rather than streptokinase compares favorably with that of other therapies whose added medical benefit for dollars spent is judged by society to be worthwhile.

Adult↗

Ten strategies to reduce blood loss in orthopedic surgery.

In any operative procedure, careful surgical dissection with precise hemostasis is one of the most effective ways to minimize surgical blood loss and reduce the need for allogeneic red blood cell transfusion. Several other techniques contribute to reduce blood loss in major orthopedic procedures. These techniques are reviewed and include rehearsal of the procedure and positioning the patient to reduce venous engorgement. In addition, a case report is presented that demonstrates the feasibility of revision hip replacement surgery without the use of transfusion in a Jehovah's Witness patient.

Adolescent↗