Effects of hyperthermia on blood flow and cis-diamminedichloroplatinum(II) pharmacokinetics in murine mammary adenocarcinomas.

The effect of localized hyperthermia on blood flow and cis-diamminedichloroplatinum(II) (CDDP) pharmacokinetics in 7,12-dimethylbenz[a]anthracene-induced mammary adenocarcinomas was studied. Blood flow was determined in rat tumors and normal tissue immediately and 1, 2, and 3 h after local hyperthermia treatment (43 degrees C, 1 h) as well as in unheated tumors of rats. The rate of blood flow in the tumor was increased 1.9 times at the end of treatment relative to control values and returned to the control values by 3 h after hyperthermia. Similarly, the rate of blood flow in the peripheral skin around the tumor immediately after hyperthermia was 2.2 times greater than that of unheated skin and returned to near normal values by 3 h after heating. Tumor-bearing rats received CDDP 1 h before, at the beginning of, at the end of, and 1 h after hyperthermia administration. The CDDP plasma concentration versus time profiles for rats did not vary statistically between treatment groups. Two h after CDDP administration, the mean tumor CDDP concentration of the rats which received drug at the beginning of hyperthermia was statistically greater (P less than 0.05) than tumor CDDP concentrations in rats which received drug at the end of heat treatment. The latter group was given CDDP when tumor blood flow was the greatest; however, mean tumor drug concentration was lowest of all the groups. The mean drug concentration in tumor tissues of rats which received drug 1 h after hyperthermia was comparable to rats which received drug at the beginning of hyperthermia. This suggests that drug delivery or uptake in tumors may be altered when local hyperthermia is administered concurrently or sequentially.     

Is bridging to transplantation with a left ventricular assist device a risk factor for transplant coronary artery disease?

BACKGROUND: Left ventricular assist device (LVAD) support is associated with coagulopathy, bleeding, increased blood transfusion, and increased anti-HLA antibody production. Increased anti-HLA antibody production is associated with early transplant rejection, transplant coronary artery disease (CAD), and decreased post-transplant survival rates. We asked whether bridging to transplantation with an LVAD increases the risk of transplant CAD. METHODS: We reviewed data for all adults (>18 years old) who underwent heart transplantation at our institution between 1988 and 2000. After exclusion of transplant recipients who survived <3 years, we divided the remaining cohort into 2 groups: those bridged to transplantation with LVADs (mean duration of support, 149 +/- 107 days, n = 29) and those in United Network for Organ Sharing Status 1 bridged to transplantation without LVADs (controls, n = 86). We compared groups in terms of disease cause, age, sex, donor age, panel-reactive antibody testing, crossmatching, pre- and post-transplant cholesterol concentrations, diagnosis of diabetes mellitus or treated hypertension, infections, calcium channel blocker use, transplant rejection, ischemic time, cytomegalovirus infection, pre-transplant transfusion, and incidence of transplant CAD (defined as any coronary lesion identified by coronary angiography). We considered p < 0.05 to be significant. RESULTS: The bridged and control groups were similar in all respects except mean ischemic time (217 +/- 58 minutes vs 179 +/- 67 minutes, p = 0.007), post-transplant cholesterol concentration (212 +/- 55 mg/dl vs 171 +/- 66 mg/dl, p = 0.007), and pre-transplant transfusion incidence (100% vs 22%, p < 0.001). The incidence of transplant CAD was similar in both groups during a 3-year follow-up period (28% vs 17%, p = 0.238) and during total follow-up (34% vs 35%, p = 0.969). Multivariate logistic regression analysis identified cholesterol concentration at 1 year after transplantation as a significant predictor of CAD at 3 years after heart transplantation (p = 0.0029, odds ratio = 0.984). CONCLUSIONS: Bridging to transplantation with an LVAD does not increase the risk of transplant CAD. Nevertheless, aggressive prophylactic therapy to minimize potential risk factors for transplant CAD, such as increased cholesterol concentration, is warranted in all transplant recipients.     

Infarction of the orbit and paranasal sinuses in sickle cell disease

We have reported the case of a 19-year-old black man with sickle cell disease who had swelling over the right frontal and periorbital areas. Plain roentgenograms and CT scans were consistent with frontal sinus disease. At trephination, however, sterile liquescent blood clot was found in the frontal sinus. Awareness of the orbital apex syndrome and infarction of the orbit and sinuses in patients with sickle cell disease is necessary to prevent misdiagnosis of these conditions as suppurative sinusitis.     

Does radical prostatectomy in the presence of positive pelvic lymph nodes enhance survival?

Summary A retrospective review was performed on all patients with stage D1 prostate cancer treated at Duke University Medical Center between 1975 and 1989. A total of 156 patients underwent staging pelvic lymph-node dissection for clinically organ-confined prostate cancer (stage A or B) but were found to have disease metastatic to the pelvic lymph nodes (stage D1). Of this population, 42 patients also underwent radical prostatectomy (group 1), leaving 114 who did not have their prostate removed (group 2). The median cancer-specific survival was 11.2 years for group 1 versus 5.8 years for group 2 (P=0.005). In patients with one or two positive lymph nodes the median cancer-specific survival was 10.2 years for group 1 versus 5.9 years for group 2 (P=0.015). There was no difference in survival if three or more lymph nodes were positive. Adjuvant treatment with immediate androgen deprivation and/or postoperative radiation therapy failed to improve the survival experience. The incidence of local problems, including stricture formation, bleeding, or regrowth of cancer requiring dilation or surgical intervention (transurethral prostatectomy) averaged 9.5% in group 1 and 24.6% in group 2. These data show that patients with limited node-positive disease selected for radical prostatectomy experience a survival advantage over those denied such therapy and that this advantage is independent of adjunctive therapy.This research was performed while Dr. Frazier was serving as a fellow in Urologic Oncology with funding from the United States Navy. The opinions herein represent those of the authors and do not necessarily reflect those of the United States Navy or the Department of Defense     

Designing the workstation for the immediate future

Conclusions Although much attention is being given to the design of the anesthesia workstation of the next century, significant opportunities exist to improve current systems. There have been sufficient technological advances that enable immediate improvement on current techniques and methodologies. As this team realized, much can be done to improve the workstation of the immediate future.     

Factors supporting idiom comprehension in children with communication disorders.

The current investigation explored understanding of idioms in context in 93 children with communication disorders and 39 age-matched peers. The clinical group was subdivided by (a) the presence of autistic features and (b) the presence of language impairment. Idiom definitions were gathered in isolation and in context. Related skills such as semantics and theory of mind were also measured. All children benefited significantly from context. However, 2 groups with language impairments (1 with and 1 without autistic features) did not benefit from context as much as the controls or a group of children with autistic features without additional language difficulties. Regression analyses found that age, memory for story context, and language abilities were significant predictors of idioms in context performance. These findings are discussed in relation to theories of idiom acquisition and contextual processing in autism.     

Object recognition by component features: are there age differences.

This study extended aspects of Biederman's (1987) recognition-by-components (RBC) theory to the analysis of age differences in the recognition of incomplete visually-presented objects. RBC theory predicts that objects are recognizable or recoverable under conditions of fragmentation if a sufficient amount of essential structural information remains available. Objects are rendered nonrecoverable by the omission or obstruction of essential structural features at vertices and areas of concavity. Fifteen young adults and 15 older adults participated in a study of the effects of amount (25%, 45%, 65%) and type of fragmentation (recoverable, nonrecoverable) on object naming. Age-related declines in recognizing incomplete objects were associated with the amount of fragmentation, but type of fragmentation did not affect the performance of older adults. For the young adults, accuracy of performance was affected by both amount and type of fragmentation, consistent with Biederman's RBC theory. These results were interpreted as suggesting that age-related declines in perceptual closure performance have to do with non-structural factors such as the ability to inferentially augment degraded or missing visual information.     

Evaluation of myocardial function in patients with end-stage heart failure during support with the Jarvik 2000 left ventricular assist device.

In 2 patients with the Jarvik 2000 left ventricular assist device (LVAD), we assessed left ventricular systolic function through pressure-volume loops and E(max) at the beginning and end of the support period to potentially predict the possibility of pump removal without transplantation. Immediately before LVAD implantation and explantation, pressure and volume measurements were made with catheters and echocardiography, respectively, the E(max) being calculated from the slope of the pressure-volume loops, and the left ventricular ejection fraction (LVEF) being estimated by echocardiography. Transplantation was performed after 14 and 62 days, respectively, during which the LVEF increased by 75% (from 12% to 21%) in Patient 1 and remained unchanged (from 16% to 18%) in Patient 2, whereas the E(max) increased from 0.63 and 0.42 mm Hg/ml, respectively, to 1.31 and 1.07 mm Hg/ml, reflecting a 107% and 155% improvement. In these 2 cases, the E(max) was a more reliable indicator of intrinsic myocardial contractility than was the LVEF.