Favorable results of coronary artery bypass grafting in patients older than 75 years

There is controversy whether the short-term and long-term results of coronary artery bypass grafting in elderly patients justify performing the procedure. Between January 1977 and December 1986, 4580 patients underwent coronary artery bypass grafting, of whom 222 (4.9%) were 75 years old or older (mean 77 years). There were 143 men and 79 women and 139 (63%) were in New York Heart Association class IV. One hundred forty-six patients (66%) had had at least one preoperative myocardial infarction. Myocardial revascularization was performed under emergency conditions in 17 patients (18%). The mammary artery was used in 43%, 96% of the patients received two or more grafts. The mean number of bypass grafts was 3.1 per patient. The overall hospital mortality rate was 10.8% (24/222), 3.6% for elective procedures, 14.9% in urgent cases, and 35% in emergencies. In contrast, the overall early mortality rate was 3.1% in 4358 patients less than 75 years old. Complications occurred in 83 patients (37%). Of the patients discharged from the hospital, 198 were followed up for a mean of 48 months (1 to 130). Actuarial probability of survival was 75% at 48 months. Postoperatively 70% were in New York Heart Association class I or II and only 21% were rehospitalized for cardiac problems. During the follow-up period 77% of the patients were free from angina, and of those experiencing angina the mean time from operation to the first episode was 75 months. Although elderly patients have a somewhat increased operative mortality rate, particularly if operated on urgently or emergently, long-term survival and freedom from angina are excellent and justify continued performance of coronary bypass grafting in selected patients over 75 years of age.     

An External Aortic Root Device for Decreasing Aortic Regurgitation: In Vitro and In Vivo Animal Studies

Objectives: The purpose of this study was to determine if a device placed externally around the aortic root decreases regurgitant flow in acute aortic regurgitation. Background: Aortic regurgitant flow is dependent on central aortic pressure and the aortic root and leaflet geometry. It may be possible to decrease aortic regurgitant severity by reducing aortic root size or dimension changes. Methods: Aortic regurgitation was created in eight calf heart specimens suspended in a continuous flow system. Retrograde and antegrade aortic flow and distending aortic pressure were measured at baseline and after placement of an external aortic device at the level of the aortic annulus. In two additional specimens, the incompetent aortic valve was visualized fiberoptically before and after placement of the external device. Acute aortic regurgitation was created surgically in four live calves by excising a portion of the aortic leaflets. Antegrade and retrograde flow, left ventricular pressure, and central aortic pressure were measured at baseline, after creation of aortic regurgitation, and after placement of the external device. Results: In the in vitro calf specimens, regurgitant flow decreased from 46.9 cc/sec to 15.1 cc/sec (66.0%± 21.8% decrease) after placement of the external device (p < 0.001). The regurgitant orifice area decreased from 0.13 ± 0.04 cm² to 0.04 ± 0.02 cm² after device placement (p < 0.001). Antegrade flow was reduced to a smaller extent (20.0%± 19.2% decrease) by the device (p < 0.05). Placement of the device around the aorta resulted in improved coaptation of the leaflets with a marked reduction in defect size by endoscopic visualization. Use of the external aortic device was associated with improvement in aortic regurgitant severity in three of four calves with surgically created aortic regurgitation. Concluslons: In these preliminary studies, acute experimental aortic regurgitant severity is decreased by the use of an external aortic device, probably due to reduction in aortic annular dimension changes and improved aortic leaflet apposition. Further studies are needed to determine the effectiveness of this device in chronic aortic regurgitation. (J Card Surg 1994;9:304–313)     

MRI demonstration and CT correlation of the brain in patients with idiopathic intracerebral calcification

Twenty-two patients aged 36–63 years were diagnosed as having Fahr's syndrome on the basis of the presence on CT of unexpected extensive calcification of the basal ganglia. Even when associated with calcification of other brain areas, the main diagnostic criterion remained basal ganglia calcification larger than 800 mm². Normal values of parathormone, serum calcium and phosphorus excluded hypercalcaemia and hypoparathyroidism. Mitochondrial CNS disease was excluded clinically. MRI and repeated CT and neurological examination were performed in all of the patients. The patients were divided into two groups: neurologically asymptomatic (group 1) and neurologically symptomatic (group 2). T2-weighted sequences demonstrated hyperintense areas in all of the patients involving the white and the grey matter of the brain. In group 1 the hyperintense lesions were significantly smaller than in group 2. The neurological symptoms correlated better with the hyperintensities on T2-weighted MR images than with the calcification demonstrated on CT. Hyperintensities in T2-weighted MRI and the areas shown by CT to have calcification had different locations. In 15 patients with dementia, the white matter of the entire centrum semiovale was bilaterally hyperintense. In another 3 patients with hemiparesis, hyperintense areas in the internal capsule, contralateral to the side of hemiparesis, were demonstrated in the T2-weighted sequence. The hyperintense T2 signals may reflect a slowly progressive, metabolic or inflammatory process in the brain which subsequently calcifies and are probably responsible for the neurological deficit observed.     

Epilepsy in patients with brain metastases triggered by intravenous contrast medium

187 patients with histologically proven primary neoplasms underwent computed tomography (CT) of the brain following intravenous administration of contrast medium. Eight developed focal epileptic seizures 2 to 4 minutes after the start of the injection. In three of these patients, in whom there was CT evidence of bilateral mass lesions of the brain, this epileptic activity became generalised into grand mal seizures, and two died in status epilepticus. In the other five patients with unilateral deposits in the brain, the focal fits corresponded to the site of the lesion shown by CT. Three of the patients had follow-up electroencephalography (EEG) examinations which showed unilateral focal activity, and their EEG foci correlated with the CT findings.     

Quantification of tissue plasma volume in the rat by contrast-enhanced magnetic resonance imaging

Magnetic resonance imaging enhanced with a macromolecular contrast medium (MMCM), albumin-Gd-DTPA, was used to estimate the plasma volume in vivo in the myocardium, lung, liver, and skeletal muscle of 10 normal rats. The plasma volumes of the same tissues in a parallel group of six rats were estimated in vitro by a conventional radioisotopic technique (¹¹¹In-transferrin). Plasma volumes of myocardium, lung, liver, and skeletal muscle estimated by the MR technique (μl plas. ia cc-¹ of tissue) were 101,109,163, and 11.0, respectively, while plasma volumes measured by the In-transferrin radioisotope technique (mg plasma g-¹ of tissue) were 78.6, 215,143, and 11-2, respectively. Assuming a ratio of densities of aerated lung to blood of 0.45 and of other tissues to blood of 1.0, correlation between the methods was excellent (R² = 0.99) indicating that MR imaging enhanced with MMCM permits reliable in vivo estimation of tissue plasma volume in the rat.     

GM-CSF induces expression of soluble VEGF receptor-1 from human monocytes and inhibits angiogenesis in mice

GM-CSF promotes homeostasis of myeloid cells. We report that GM-CSF upregulates mRNA and protein production of the soluble form of membrane bound VEGF receptor-1 (sVEGFR-1) in human monocytes. This sVEGFR-1 was biologically active, as cell-free supernatants from GM-CSF-stimulated monocytes blocked detection of endogenously expressed VEGF and inhibited endothelial cell migration and tube formation, even in the presence of exogenous rhVEGF. VEGF activity was recovered by neutralizing sVEGFR-1. To determine whether these events were important in vivo, Matrigel plugs were incubated with rhVEGF, rhGM-CSF, or rhGM-CSF/rhVEGF and injected into mice. Plugs containing GM-CSF or GM-CSF/VEGF had less endothelial cell invasion than plugs containing rhVEGF and were similar to plugs incubated with PBS alone. Neutralizing antibodies specific for sVEGFR-1 injected in these plugs reversed the effects of GM-CSF or GM-CSF/VEGF, while an isogenic antibody did not. Thus, GM-CSF and monocytes play a vital role in angiogenesis through the regulation of VEGF and sVEGFR-1.     

Lesser response to angiotensin-converting-enzyme inhibitor therapy in black as compared with white patients with left ventricular dysfunction

BACKGROUND: Black patients with heart failure have a poorer prognosis than white patients, a difference that has not been adequately explained. Whether racial differences in the response to drug treatment contribute to differences in outcome is unclear. To address this issue, we pooled and analyzed data from the Studies of Left Ventricular Dysfunction (SOLVD) prevention and treatment trials, two large, randomized trials comparing enalapril with placebo in patients with left ventricular dysfunction. METHODS: We used a matched-cohort design in which up to four white patients were matched with each black patient according to trial, treatment assignment, sex, left ventricular ejection fraction, and age. A total of 1196 white patients (580 from the prevention trial and 616 from the treatment trial) were matched with 800 black patients (404 from the prevention trial and 396 from the treatment trial). The average duration of follow-up was 35 months in the prevention trial and 33 months in the treatment trial. RESULTS: The black patients and the matched white patients had similar demographic and clinical characteristics, but the black patients had higher rates of death from any cause (12.2 vs. 9.7 per 100 person-years) and of hospitalization for heart failure (13.2 vs. 7.7 per 100 person-years). Despite similar doses of drug in the two groups, enalapril therapy, as compared with placebo, was associated with a 44 percent reduction (95 percent confidence interval, 27 to 57 percent) in the risk of hospitalization for heart failure among the white patients (P<0.001) but with no significant reduction among black patients (P=0.74). At one year, enalapril therapy was associated with significant reductions from base line in systolic blood pressure (by a mean [+/-SD] of 5.0+/-17.1 mm Hg) and diastolic blood pressure (3.6+/-10.6 mm Hg) among the white patients, but not among the black patients. No significant change in the risk of death was observed in association with enalapril therapy in either group. CONCLUSIONS: Enalapril therapy is associated with a significant reduction in the risk of hospitalization for heart failure among white patients with left ventricular dysfunction, but not among similar black patients. This finding underscores the need for additional research on the efficacy of therapies for heart failure in black patients.     

Do proficiency test results correlate with the work performance of screeners who screen Papanicolaou smears?

We rescreened Papanicolaou smear slides from 40,245 women, which had been examined by 81 cytology screeners, scored the screeners' work performance, and compared these scores with the results of the screeners' performance on glass slide and computer-based proficiency tests. All diagnoses (i.e., from the proficiency tests, the original slides, and the rescreened slides) were classified in the 4 diagnostic categories specified in the Clinical Laboratory Improvement Amendments. The rescreening scores were standardized to account for different distributions of abnormalities in the proficiency tests and rescreened slides. We compared a standardized score with the proficiency test scores. Of the cases, 91% were categorized as normal, benign, or reactive changes when rescreened, and 98% of these agreed with the original diagnosis. Sixteen percent of low-grade and 15% of high-grade intraepithelial lesions were classified as normal. The rank correlation between the rescreening scores and both proficiency tests was 0.24 using a scoring scheme for cytotechnologists. The correlation between the rescreening and proficiency testing scores indicates that performance on a 10-slide test gives some indication of the true performance of screeners. The computer-based test shows promise as an alternative to the glass slide test but needs further development and validation.     

A biological context for the self-nonself discrimination and the regulation of effector class by the immune system

An effective immune response to an antigen requires two sets of decisions: Decision 1, the sorting of the repertoire, and Decision 2, the regulation of effector class. The repertoire, because it is somatically generated, large, and random, must be sorted by a somatic mechanism that subtracts those specificities (anti-self) that, if expressed, would debilitate the host, leaving a residue (anti-nonself) that, if not expressed, would result in the death of the host by infection. The self-nonself discrimination is the metaphor used to describe Decision 1, the sorting of the repertoire. In order to be functional, the sorted repertoire must be coupled to a set of biodestructive and ridding effector functions, such that the response to each antigen is treated in a coherent and independent manner. Although a reasonably complete framework for Decision 1 exists, Decision 2 lacks conceptualization. The questions that must be considered to arrive at a proper framework are posed. It should be emphasized that manipulation at the level of Decision 2 is where clinical applications are likely to be found.