Detection of Barrett's adenocarcinoma of the gastric cardia with sucrase isomaltase and p53.

BACKGROUND: Routine surveillance for dysplastic epithelium in patients with Barrett's esophagus has markedly improved prognosis. Many patients with short segments of Barrett's mucosa near the esophagogastric junction remain undiagnosed and at risk for the development of Barrett's adenocarcinomas (BA). Sucrase isomaltase (SI), an intestinal enzyme, is highly expressed in intestinal-type Barrett's mucosa and frequently expressed in dysplastic Barrett's mucosa and BA. Sucrose isomaltase is not expressed in normal esophageal or gastric mucosa. Alterations in the p53 tumor suppressor gene are frequent events in dysplastic Barrett's mucosa and BA and result in nuclear protein accumulation. The purpose of this study was to determine the presence or absence of these markers of Barrett's mucosa in adenocarcinoma of the esophagogastric junction or cardia. METHODS: Expression of SI and p53 were examined in 40 BAs and 25 cardia adenocarcinomas using immunohistochemical techniques. RESULTS: Sucrose isomaltase analysis revealed positive staining in 55% (22/40) of the BAs and 44% (11/25) of the cardia adenocarcinomas. Of 14 cardia adenocarcinomas that were SI negative, 100% (14/14) had no associated Barrett's mucosa. However, in 21 cardia adenocarcinomas with no associated Barrett's mucosa, 7/21 (33%) were SI positive. This suggests that SI-positive tumors may represent BA without the standard definition of Barrett's esophagus being met. P53 was present in 65% of BAs and 64% of cardia adenocarcinomas, demonstrating the importance and similarity of this gene alteration in both tumor types. Staining was positive for SI or p53 in 77% (50/65) of all tumors. Tumors of lower stage expressed SI more often than higher stage tumors. CONCLUSIONS: These data suggest that a subset of cardia adenocarcinomas represent BAs. Surveillance endoscopy incorporating additional esophagogastric junction biopsies and assessment of SI or p53 may improve detection of intestinalized Barrett's mucosa and early dysplastic changes.

Coronary artery bypass grafting in patients with dialysis-dependent renal failure.

Few data exist regarding functional results and long-term survival after coronary bypass in patients on dialysis. Therefore, a retrospective analysis was performed of 21 consecutive patients with dialysis-dependent renal failure who were undergoing coronary artery bypass grafting. Preoperatively, all but 1 patient had associated comorbid illnesses, 15 patients (71%) had class IV angina, and 16 patients (76%) had either left main or three-vessel disease. There were two perioperative deaths (9%), and complications occurred in 10 of the 21 patients (48%). All 19 hospital survivors showed symptomatic improvement with improved overall functional status (mean Karnofsky score increased from 37% +/- 16% preoperatively to 69% +/- 9% at hospital discharge or death; p < 0.001). Actuarial survival rates were 84% +/- 8% and 45% +/- 13% at 1 and 2 years, respectively. Therefore, coronary bypass grafting may be performed in dialysis patients with increased but acceptable morbidity and mortality, with excellent symptomatic relief, and with improved functional status. However, limited long-term survival suggests that the relative costs and benefits of surgical revascularization need further examination in this patient population.

Recovery of myocardial function during coronary artery bypass grafting. Intraoperative assessment by pressure-volume loops.

Radionuclide angiocardiography and left ventricular manometry were performed simultaneously in 12 men undergoing elective coronary artery bypass grafting. Pressure-volume loops constructed from these data allow calculation of stroke work and provide a more complete description of global left ventricular function immediately before cardiopulmonary bypass and at a mean of 18 and 34 minutes after termination of ischemic arrest. Early reperfusion was characterized by significant elevation of end-diastolic pressure (p less than 0.01) without a corresponding increase in end-diastolic volume. With continued reperfusion, end-diastolic volume, calculated stroke work, and cardiac output increased significantly with respect to control (p less than 0.05). Heart rate, ejection fraction, mean arterial pressure, stroke work/end-diastolic volume, and maximal dP/dt remained unchanged during the study period. No new focal abnormalities were detected in regional wall motion. These data indicate that minimal residual impairment of diastolic function exists during the acute recovery from cardioplegic arrest and bypass grafting but improves with further reperfusion. Systolic function appears to normalize more rapidly than diastolic function after ischemic arrest.

The effect of nitroglycerin on response to tracheal intubation. Assessment by radionuclide angiography.

The effect of intravenous (IV) nitroglycerin (NTG) on perioperative myocardial ischemia as detected by single pass radionuclide angiocardiography was studied in 20 patients scheduled for elective coronary artery bypass grafting (CABG). Ten patients, selected at random, received IV NTG 1 microgram.kg-1.min-1 (NTG group) and 10 others, IV saline (control group). Anesthetic induction consisted of midazolam 0.2 mg.kg-1, vecuronium 0.1 mg.kg-1, and 50% N2O in O2. ECG leads I, II, and V5 were monitored for ST segment changes. Single pass radionuclide angiocardiography (RNA) was performed at 5 times: prior to induction, prior to tracheal intubation, and at 1, 3.5, and 6 min following intubation. The presence of new regional wall motion abnormalities (RWMA) was determined from each RNA study as compared with the preinduction measurement. Apart from one patient in the control group who developed a new "v" wave after intubation, there was no evidence of ischemia by pulmonary capillary wedge pressure. No ECG evidence of ischemia was detected in any patient. Despite this, new regional wall motion abnormalities were observed in 3 patients in the control group and 1 patient in the NTG group. Blood pressure and heart rate responses of patients with new RWMA were not significantly different from other patients. The low incidence of ischemia in this population precludes a definitive statement regarding the efficacy of IV NTG, but the lower incidence of RWMA in the NTG group suggests a protective effect.

A new method to determine left ventricular pressure-volume loops in the clinical setting.

Left ventricular pressure-volume (P-V) loops provide a complete definition of cardiac performance but have been difficult to obtain in the clinical setting. Accordingly, we have developed a new technique for acquiring P-V loops during and after cardiac surgical procedures using portable first-pass radionuclide angiocardiography coupled with intraventricular micromanometer catheters. Using this technique 35 serial left ventricular P-V loops were acquired in 12 patients during and after coronary artery bypass grafting. Dynamic radionuclide left ventricular volume and micromanometer pressure were acquired simultaneously to generate the P-V loops. Moreover, simultaneous measurement of both volume and pressure allowed comparison of the timing of end diastole (ED) and end systole (ES) defined by each of the two cardiac parameters. For 208 EDs and 243 ESs analyzed volume-defined ED occurred 8 +/- 27 msec (s.d.) later in the cardiac cycle than pressure-defined ED while volume-defined ES occurred 29 +/- 27 msec (s.d.) earlier than pressure-defined ES. It is concluded that measurement of cardiac P-V loops with this new technique is clinically feasible and that a close agreement has been demonstrated between the timing of cardiac events defined either by volume or pressure criteria.

Recognition of reversible and irreversible myocardial injury by technetium pyrophosphate extraction kinetics.

The need for a more accurate method of detecting episodes of myocardial ischemia during cardiac operations, particularly during the ischemic arrest interval, prompted us to investigate the usefulness of measuring the active extraction of technetium pyrophosphate in identifying and quantitating ischemic injury. Twenty-four adult mongrel dogs were subjected to cardiopulmonary bypass, and normothermic global ischemia was induced by cross-clamping the proximal aorta. Technetium pyrophosphate (1 mCi) was injected through a standard cardioplegia line with normal saline, simulating administration of cardioplegic solution, upon placement of the aortic cross-clamp (time 0), at 15, 30, 45, and 60 minutes of global ischemia, and with the onset and completion of ischemic contracture. Radioactive counts were recorded over the heart at 1 second intervals, and the extraction fraction and half-time of clearance were calculated. The extraction fraction increased from 0.22 at time 0 to 0.58 at 15 minutes, 0.82 at 30 minutes, 0.85 at 45 minutes, and 0.91 at 60 minutes. The halftime increased from a baseline of 114 seconds (time 0) to a maximum of 321 seconds at 60 minutes of ischemia. The onset and completion of ischemic contracture showed a return toward baseline of both the extraction fraction and halftime of clearance, with an extraction fraction of 0.44 and 0.46 and a halftime of 135 and 133 seconds, respectively. These data clearly show that reversible myocardial injury increased the extraction and reduced the clearance of technetium pyrophosphate and that the magnitude of change related to the extent of injury. The progression to irreversible myocardial injury decreased the active extraction of technetium pyrophosphate. This simple procedure for real-time documentation of myocardial injury promises to provide easily obtainable endpoints of injury for use during cardiac operations in humans.

Protothecal olecranon bursitis: treatment with intrabursal amphotericin B.

A patient is described from whom repeated olecranon bursa fluid cultures yielded Prototheca wickerhamii. Following intrabursal instillation of amphotericin B, the cultures became negative. There was no progression of infection or adverse consequences of this treatment. Review of the literature regarding this unusual infection reveals seven reported cases of protothecal olecranon bursitis. Five cases from which sufficient information was provided were diagnosed by histologic examination of excised bursa that showed the characteristic sporangia.

Nosocomial Clostridium difficile reservoir in a neonatal intensive care unit.

A new bacteriophage/bacteriocin typing system was used to study Clostridium difficile colonization in a neonatal intensive care unit. C. difficile was isolated from 21 of 62 (34%) stools from 15 of 37 (41%) infants. Colonization was reduced during antimicrobial therapy and for about 1 week thereafter. One of five nurses and one of two parents studied were carriers. Eight isolates were cultured from environmental surfaces. Thirty of 31 C. difficile isolates were found to be a single type, Cld 6,9,10,13; bacteriocin 1320,1537,2304. No C. difficile was found in 29 specimens obtained in the delivery room from mothers and infants, and there was no association of early colonization with vaginal delivery. The data provide strong evidence for nosocomial acquisition of C. difficile by infants in the neonatal intensive care unit. No obvious pathologic role for C. difficile could be identified among colonized infants. Among 22 C. difficile isolates from 7 adult inpatients with diarrhea and 13 healthy infants attending the center's well baby clinic, 4 were the same type as the strain found in the intensive care nursery. Only one of these patients had had direct contact with the neonatal intensive care unit, indicating that the nursery strain may also be found elsewhere in the community.

Effect of therapy with latamoxef (moxalactam) on carriage of Clostridium difficile.

Twenty-seven patients receiving latamoxef (moxalactam) as a single antimicrobial agent were studied prospectively for Clostridium difficile carriage and development of diarrhoea or colitis. Stools were available prior to therapy from only seven patients, one of whom (14.3%) was an asymptomatic carrier. None of twelve patients studied during therapy were carriers. Seven of 27 patients (25.9%) were colonized with Cl. difficile after completion of latamoxef therapy, and three patients had cytotoxin positive stools. Two patients with cytotoxin grew Cl difficile from stools and one patient was culture negative. Only one patient, who had both culture and cytotoxin positive stools, had profuse diarrhoea. Cl. difficile clinical isolates were only moderately susceptible to latamoxef in vitro. Hamsters given moxalactam developed caecitis. Patients receiving latamoxef, or third generation cephalosporins, may be at increased risk of development of Cl. difficile associated diarrhoea and should be followed closely for this complication, especially after therapy has been discontinued.

Bacteriophage and bacteriocin typing scheme for Clostridium difficile.

The study of the epidemiology of infection with Clostridium difficile would be aided by a way to type individual bacterial isolates. We therefore sought bacteriophages for use in typing. With mitomycin C exposure (3 micrograms/ml), filtrates from 10 strains of C. difficile had plaque-forming lytic activity on other C. difficile strains. Individual phage were passaged and made into high-titer stock preparations for typing. Electron microscopy revealed tailed phage particles from one such preparation. In addition to phage, inhibitory activity without distinct plaque formation consistent with bacteriocins was observed for 20 strains. C. difficile isolates from 16 patients taken 1 to 14 days apart were similar in their phage sensitivity pattern, whereas isolates from separate geographic locations showed a great variety of patterns. We conclude that bacteriophage should be useful for typing strains of C. difficile.

In vitro evaluation of inhibitors of platelet release and aggregation.

In order to determine which drugs would be most effective as inhibitors of platelet release and aggregation, in vitro release reactions and platelet aggregometry were used to evaluate aspirin, dipyridamole, sulfinpyrazone, flurbiprofen, low molecular weight dextran (dextran 40), prostaglandin E1 (PGE1), apyrase, and adenosine. Adenosine diphosphate-induced aggregation was most effectively inhibited by PGF1, sulfinpyrazone, and dipyridamole. The latter had to be used in large doses. Collagen and epinephrine-induced release and aggregation were inhibited by the same drugs as well as by aspirin and apyrase. Antihynocyte globulin (ATG)-induced release and aggregation could only be partially blocked by these agents. In vitro studies suggest that sulfinpyrazone is one of the most effective of platelet inhibitors currently available for clinical testing.