Biomedical subjects
Publications and source records attributed to A C Beall.
Esophagectomy after pneumonectomy has been reported rarely, and the surgical approach presents a challenge. We report a case of a transthoracic esophagectomy in a 54-year-old man who had undergone right pneumonectomy for non-small cell lung cancer 16 years previously.
BACKGROUND: Elderly surgical patients have higher operative morbidity and mortality than younger cohorts, particularly when the procedure is lengthy and complex. While use of bilateral internal thoracic arteries (BITA) is often associated with increased surgical risk, we nevertheless hypothesized that the use of BITA in elderly coronary artery bypass patients would not significantly increase their operative risk beyond that encountered using single internal thoracic arterial (SITA) or saphenous vein grafts (SVG). We maintained that arterial grafts remain essentially unaffected by arteriosclerosis, and that extension of a high-quality life is a desirable outcome regardless of age at operation. METHODS EXPERIMENTAL DESIGN: We studied myocardial revascularization in 673 patients over 65 years of age at the time of operation. All operations were conducted or supervised by a single surgeon during a ten-year period from January 1986 to January 1996. Preoperative and operative dates were recorded prospectively. SETTING: All patients underwent coronary artery bypass grafting. INTERVENTIONS: The study compared outcomes in patients having all veins, SITA or BITA operations. For the first analysis, 673 patients were divided into three groups: 163 patients (Group 1) had saphenous vein used for all bypasses; 338 patients had a SITA with supplemental vein grafts (Group 2); and 172 patients (Group 3) had BITAs with additional vein grafts as needed. In the second analysis, Group 3 was subdivided and grouped by the coronary arteries which received the ITA grafts, and the analysis was repeated. One hundred and sixteen patients (Group 3A) underwent traditional placement of ITA bypasses (left ITA to the LAD, right ITA to the RCA); in Group 3B, 56 patients received revascularization of branches of the left coronary artery (left ITA to the circumflex system, right ITA to the LAD). MEASURES: We communicated directly with 90.5% of the patients, their families, or their physicians. The survival status of the remainder was determined through the National Social Security Death Index Network. This allowed us to obtain follow-up longevity data for 100% of the study sample at a mean observation period of 5.03+/-3.1 years with variation between 10.8 years to 2.4 years. RESULTS: A multivariate analysis showed that placement of both ITA grafts to left-sided arteries in older patients independently improved long-term survival (p=0.031). CONCLUSIONS: The BITA procedure does not have greater operative morbidity or mortality in the elderly despite the length or complexity of the surgery. To realize improved long-term survival rates, however, both ITAs must be grafted to the left coronary artery branches.
Immersive virtual environment (IVE) technology has great promise as a tool for basic experimental research in psychology. IVE technology gives participants the experience of being surrounded by the computer-synthesized environment. We begin with a discussion of the various devices needed to implement immersive virtual environments, including object manipulation and social interaction. We review the benefits and drawbacks associated with virtual environment technology, in comparison with more conventional ways of doing basic experimental research. We then consider a variety of examples of research using IVE technology in the areas of perception, spatial cognition, and social interaction.
Activation of cyclic nucleotide-dependent signaling pathways leads to the relaxation of various smooth muscles. One of the major phosphorylation events associated with cyclic nucleotide-dependent vasorelaxation in bovine trachealis and carotid artery smooth muscle is the phosphorylation of two 20-kDa phosphoproteins with pI values of 5.7 and 5.9 (previously designated pp8 and pp3, respectively). The present studies sought to determine the identities of pp3 and pp8 in vascular smooth muscle. The phosphopeptide maps for the pp8 and pp3 proteins were similar. Preparative two-dimensional gel electrophoresis and amino acid sequencing of a peptide fragment of the pp3 protein revealed a sequence identical to a 20-kDa heat shock-related protein (HSP20) previously purified from skeletal muscle. Western blot and immunoprecipitation analysis with anti-HSP20 antibodies demonstrated that the pp3 and pp8 proteins are phosphorylated forms of HSP20. In addition, HSP20 could be phosphorylated in vitro by both cAMP-dependent protein kinase and cGMP-dependent protein kinase. These data suggest that the phosphorylation of the heat shock-related protein HSP20 is associated with cyclic nucleotide-dependent relaxation of vascular smooth muscle.
BACKGROUND: Origin of the left circumflex coronary artery from the right sinus of Valsalva is the most common anatomic variation of the coronary artery circulation. However, there are few reports about the operative approach to this anomalous vessel. METHODS: Forty patients having this anomaly were identified from 10,216 adult cardiac catheterization procedures. Forty percent of the anomalous circumflex coronary arteries (ACCAs) had critical atherosclerotic lesions. Eighty cases needed bypass grafting. RESULTS: For diagnosis of ACCA, the aortic root sign was positive in 94.9% of the diagnosed patients and the nonperfused myocardium sign was found in 92.5%. Eighty percent of ACCAs were larger than 2 mm in radiographic diameter before their passage into the atrioventricular groove. However, after emerging from the atrioventricular groove, 70% measured less than 1.5 mm. Consequently, a technique was developed to bypass the proximal ACCA and was used in 2 cases. Six other patients with more distal disease and larger vessels underwent conventional bypass grafting. CONCLUSIONS: The aortic root sign and nonperfused myocardium are useful in diagnosing ACCA. The ACCA is usually too small for use of the conventional graft technique. Therefore, a technique was developed to graft more proximally and was applied successfully in 2 cases.
BACKGROUND: Although conceptually sound, the use of multiple internal thoracic artery (ITA) bypass grafts to improve long-term clinical results remains controversial. This operation typically involves grafting the left ITA to the anterior descending artery and the right ITA to the right coronary artery. Past clinical studies of bilateral ITA operations have not examined comparative results associated with which coronary arteries received the ITA bypass grafts. Because grafting a superior conduit to an artery of lesser physiologic importance might reduce the clinical benefits, we compared the outcomes of patients receiving different configurations of bilateral ITA operations. METHODS: The study group was 498 consecutive bilateral ITA operations, constituting the 10-year experience of a single surgeon. Follow-up averaged 7.1 years (mode 7.3 years), and was 94.2% complete. These patients were divided into two groups, 311 patients (group I) who underwent the traditional operation (left ITA to the left anterior descending artery, right ITA to the right coronary artery), and 187 patients (group II) who received revascularization of branches of the left coronary artery (left ITA to the circumflex system and right ITA to the left anterior descending artery). RESULTS: The study groups were similar in age, severity of disease, number of bypassed arteries, ejection fraction, diabetes, hypertension, and duration of operation. There were more male patients in group II (91.4% versus 82.3%). A multivariate analysis showed that the location of ITA bypass grafts influenced survival independent of gender (p = 0.0288). Operative morbidity and mortality were similar between groups. Ninety-three patients had repeat angiography with equivalent patency rates of the ITA conduits (91.7% versus 89.6%; p = 0.67). The Kaplan-Meier actuarial survival estimate demonstrated a significant improvement in survival of patients in group II who received both ITA bypass grafts to left-sided arteries (p = 0.021), with the survival curves diverging at 6 years. More patients in group II were in New York Heart Association class I or II, but the difference was not statistically significant (94.6% versus 91.6%). Only 2 patients required reoperation. CONCLUSIONS: It appears that maximum long-term benefit from bilateral ITA operations is achieved by grafting the ITA conduits to coronary arteries that supply more left ventricular muscle.
Right bundle branch block following coronary surgery is a common occurrence. Among 759 coronary surgery cases, 104 patients (13.7%) had a new right bundle branch block. Of these right bundle branch blocks, 62 were transient, and 42 (40.4%) were permanent. The large number of bypasses (3.20 versus 2.75, P = 0.0001) and stenosis of the right coronary artery (81.7% versus 66.5%, P = 0.003) was strongly associated with a new right bundle branch block. In the analysis of the permanent right bundle branch block, blood cardioplegia prevented the block from becoming permanent (35.7% versus 75.8%, P = 0.0001). Therefore, it is concluded that perioperative right bundle branch block occurs predominantly in patients who have a critical stenosis in an artery which supplies the conduction system and in those undergoing more extensive procedures. In addition, blood cardioplegia affects the conduction system less severely than does crystalloid cardioplegia.
OBJECTIVE: The authors evaluate operative and extended outcomes of coronary artery bypass surgery using the bilateral internal thoracic arteries (ITAs) as bypass grafts. The authors conclude that the procedure is viable and of long-term benefit to most patients. SUMMARY BACKGROUND DATA: Multiple ITA grafting was met with early enthusiasm by the surgical profession, but skepticism and controversy arose with reports of increased operative morbidity, insufficient graft blood flow, a high incidence of failure of the right ITA, and uncertainty about durability and long-term benefits. METHODS: To assess the actual incidence and impact of these complications and long-term results, the authors prospectively studied 500 consecutive patients with multiple ITA bypasses, constituting the closely observed and carefully documented experience of one surgeon over an 11-year period. RESULTS: Operative mortality in the series of 500 patients was 1.8%, perioperative myocardial infarction (new Q wave) rate was 0.6%, and deep sternal wound infection occurred in 1%. Six patients (1.2%) had strokes, and nine patients (1.8%) were returned to the operating room to control bleeding. One hundred ninety-eight patients who had abnormal stress test results before surgery were retested within 3 months of surgery. Ninety-four percent of these were normal, 3% were nondiagnostic, and 3% were abnormal. After a mean follow-up of 7.1 years (mode, 7.2 years), 87.5% of patients in the sample were alive, and 93.2% of this group have experienced continuing good clinical results (New York Heart Association class I or II). Eighty-nine patients who underwent an angiogram had 90.8% patency rates of ITA bypasses and 84.5% patency of vein grafts. Only two patients required repeat operations. CONCLUSIONS: The operative results did not support the contention that the coronary artery bypass using ITA procedure produces higher than acceptable mortality and morbidity rates. Multiple ITA bypasses can be performed without excessive morbidity, with low reoperation rates and long-term outcomes that should encourage skeptics to reconsider the procedure's clinical value.
We provide experimental evidence that perceived location is an invariant in the control of action, by showing that different actions are directed toward a single visually specified location in space (corresponding to the putative perceived location) and that this single location, although specified by a fixed physical target, varies with the availability of information about the distance of that target. Observers in two conditions varying in the availability of egocentric distance cues viewed targets at 1.5, 3.1, or 6.0 m and then attempted to walk to the target with eyes closed using one of three paths; the path was not specified until after vision was occluded. The observers stopped at about the same location regardless of the path taken, providing evidence that action was being controlled by some invariant, ostensibly visually perceived location. That it was indeed perceived location was indicated by the manipulation of information about target distance--the trajectories in the full-cues condition converged near the physical target locations, whereas those in the reduced-cues condition converged at locations consistent with the usual perceptual errors found when distance cues are impoverished.
The CD16 receptor (Fc gamma R-III) is found on many tissue macrophages (M phi s), but its expression on circulating monocytes is restricted to a small, phenotypically distinct subset. The number of these CD16+ monocytes may be markedly increased in response to sepsis, human immunodeficiency virus infection, or metastatic malignancy. We have recently shown that the CD16+ monocyte population is selectively expanded by administration of recombinant human macrophage colony-stimulating factor (rhM-CSF). In the current study, we used the highly rhM-CSF-responsive cynomolgus primate model to further characterize this novel monocyte population. Animals treated with rhM-CSF underwent a progressive and essentially complete conversion to the CD16+ monocyte phenotype, with up to a 50-fold increase in the number of CD16+ cells. This increase was paralleled by the emergence of a population of circulating cells that morphologically resembled large granular lymphocytes (LGLs). However, quantitatively, this population corresponded closely to the number of CD16+ monocytes, and fluorescence-activated cell sorting (FACS) confirmed that they were the same. In addition to their LGL-like morphology, many rhM-CSF-induced CD16+ monocytes showed a pattern of size, granularity, and quantitative cell surface marker expression that closely resembled the pretreatment LGL/natural killer (NK) cell population but that did not resemble the pretreatment monocyte population. However, rhM-CSF-induced CD16+ monocytes could be distinguished from LGL/ NK cells by fact that they all expressed cell surface receptors for rhM-CSF, and many of them showed reduced but detectable phagocytic and respiratory burst activity. Studies of human subjects treated with rhM-CSF also showed an analogous population of "LGL-appearing" CD16+ mononuclear cells. Thus, our studies reveal a previously unsuspected ability of cells in the monocyte lineage to adopt a phenotype similar to that of LGL/NK cells. The extent of this phenotypic convergence suggests that the two lineages retain access to elements of a similar developmental pathway.
The self-reactive T cells that escape clonal deletion in the thymus must be suppressed by the less well characterized process of peripheral tolerance. In this study, we show that monocyte-derived macrophages (M phi) undergoing terminal differentiation in the presence of macrophage CSF (M-CSF) acquire the ability to selectively induce apoptosis of T cells in an activation-specific fashion. Lymphocytes were stimulated via the TCR using anti-CD3 cross-linking, staphylococcal superantigen, or allogeneic mixed-leukocyte cultures. T cells activated while in contact with M-CSF-derived M phi exited the resting G0 state and re-entered the cell cycle, but experienced a sustained arrest near the first G1/S transition, followed by progressive apoptosis. In contrast, lymphocytes that were not stimulated remained viable, and could later activate normally when removed from contact with M phi. Functionally, exposure of T cells to alloantigens presented by M-CSF-derived M phi resulted in a selective depletion of the alloresponsive T cell population, while preserving reactivity to other mitogens and to alloantigens from different donors. The ability of M phi to impose activation-induced apoptosis on lymphocytes was regulated developmentally, being absent in fresh monocytes, progressively acquired during differentiation in M-CSF, and abrogated if monocytes were exposed to IFN-gamma before differentiation. We speculate that this novel interaction may help to selectively delete autoreactive T cells that respond to self Ags presented by noninflammatory tissue M phi.
Isolated right ventricular aneurysms are rare. Postinfarction right ventricular aneurysm associated with a ventricular septal defect is a very unusual complication. We present such a case that was successfully treated surgically.
The case of a mild hemophiliac who underwent a successful and uncomplicated myocardial revascularization is presented. The procedures was safely performed while the patient was receiving factor VIIIC.
An analysis and experimental evidence are presented that the visual control of steering in following a straight demarcated path is possible even when information about the direction of one's travel (course) is not available. Two likely sources of optical information available to observers are considered, bearing and splay, that might be used for steering under these conditions. In an experiment involving a computer-driven driving simulator, observers attempted to steer a straight path while subjected to lateral perturbing forces. When only bearing and its time derivative, motion parallax, were available, performance fell off as expected with the optical gain of motion parallax as the preview distance of the viewing aperture was varied. When splay angle and its time derivative, splay rate, were added to the display, performance generally improved and remained relatively constant with changing distance of the viewing aperture, as expected because of the constant optical gain of splay rate. Making course information available by adding point features to both displays improved steering performance only in the motion-parallax conditions.
Heat exchange methods must be efficient in order to minimize the patient's pump time. However, comparisons of heat exchangers have been rare. Therefore, the in vivo functions of the most popular, currently available heat exchangers, Sarns, Cobe, Medtronics Maxima, and an experimental model manufactured by Haemonetics were compared. Thirty-two pigs weighing between 63-74 kg were placed on cardiopulmonary bypass with right atrial and ascending aorta cannulation through a right thoracotomy. Thermocouples were placed in the pump tubing before and after the heat exchangers, in the water line before and after the heat exchangers, in the inlet and outlet line of the pump, and the esophagus, brain, bladder, rectum, liver, myocardium, and tympanic membranes of the pigs. They were cooled until the bladder temperature was reduced to 14 degrees C, and maintained at that temperature for 10 minutes. Rewarming was begun until the bladder temperature became 37 degrees C. The pump flow was maintained between 50-60 ml/kg/min with standard ventilation. Cobe, Sarns, Maxima, and Haemonetics heat exchangers were tested and their function determined by comparing the time necessary for rewarming. The Haemonetics heat exchanger required a significant shorter time than the others to rewarm the pigs to normal bladder temperature (Cobe 82.0 +/- 12.0, Sarns 80.3 +/- 15.4, Maxima 89.0 +/- 13.9 Haemonetics 68.7 +/- 13.4, p < 0.05). The principal advantage was seen at the lowest temperatures between the Haemonetics experimental heat exchanger and the other heat exchangers. No statistically significant superiority was seen at higher temperatures. The current heat exchangers are relatively comparable but improved performance is possible with available technology.
The small subset of circulating monocytes that express the maturation-associated CD16 antigen has recently been reported to be elevated in patients with bacterial sepsis. We now show that this novel CD16+ monocyte population is also spontaneously expanded in patients with cancer. We studied 14 patients with metastatic gastrointestinal carcinoma enrolled ina clinical trial of recombinant human macrophage colony-stimulating factor (rhMCSF) plus monoclonal antibody D612. We found that before any cytokine treatment, 12 of 14 patients constitutively displayed significant elevations in both the percentage and the absolute number of CD16+ monocytes, as compared with both normal subjects and ill patients with elevated monocyte counts but without malignancy. CD16+ monocytes accounted for 46% +/- 22% of total monocytes in the patients with cancer versus 5% +/- 3% for controls (P < .01). The increase was not attributable to infection or intercurrent illness and appeared to be associated with the underlying malignancy itself. A similar spontaneous elevation of CD16+ monocytes was observed in 35 of 44 additional patients diagnosed with a variety of other solid tumors. When patients with gastrointestinal carcinoma were treated with rhMCSF, there was a marked further increase in the percentage of CD16+ monocytes (to 83% +/- 11%), as well as in the absolute number of CD16+ cells and the level of CD16 antigen expression. In every case, the patients with cancer showed a greater CD16+ monocyte response than the maximal response obtained in normal volunteer subjects treated witha similar regimen of rhMCSF (n = 5, P < .001), suggesting that the presence of malignancy primed patients for enhanced responsiveness to rhMCSF. We hypothesize that spontaneous expansion of the CD16+ monocyte population may represent a novel biologic marker for a widespread and previously unsuspected host immune response to malignancy.
Activated macrophages (M phi s) are important participants in host defense, but their uncontrolled activation leads rapidly to septic shock and death. One mechanism for regulating other dangerous cells in the immune system is programmed cell death, or apoptosis. Monocytes are known to undergo spontaneous apoptosis upon leaving the circulation unless provided with specific survival signals, but mature tissue M phi s are more robust cells, and it was not clear that they could be similarly regulated by apoptosis. We now show that during differentiation monocytes rapidly lose their sensitivity to apoptosis triggered by passive cytokine withdrawal, but they may retain a novel pathway which initiates apoptosis after activation with specific stimuli (zymosan and phorbol esters). Sensitivity to activation-induced apoptosis was developmentally determined, being downregulated by the maturation-promoting cytokine macrophage colony-stimulating factor but stably upregulated by even transient exposure to the proinflammatory cytokine interferon gamma (IFN-gamma). Apoptosis began within 2-4 h of activation, occurred in > 95% of susceptible cells, and in mixed cocultures selectively affected only those M phi s with a history of IFN-gamma priming. Consistent with a possible role for protein kinase C in the signaling pathway leading to cell death, the kinase inhibitor staurosporine was protective against both phorbol ester- and zymosan-induced apoptosis. Our studies describe a novel form of activation-induced M phi apoptosis which is developmentally regulated by two physiologically relevant cytokines. We speculate that apoptosis may serve to restrict the destructive potential of inflammatory M phi s.
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