Long-term outcomes of thymosin-alpha 1 and interferon alpha-2b combination therapy in patients with hepatitis B e antigen (HBeAg) negative chronic hepatitis B.

Hepatitis B e antibody (HbeAb) and hepatitis B virus (HBV) DNA positive chronic hepatitis is a clinical entity, distinct from classical hepatitis B e antigen (HbeAg) positive chronic hepatitis B. Our aim was to evaluate the long-term therapeutic efficacy of the combination of interferon alpha-2b and thymosin-alpha1 compared with lamivudine plus interferon alpha-2b and interferon alpha-2b alone. Fifty-two patients with HbeAg-negative chronic hepatitis B were assigned to three different groups in a nonrandomized manner. Group 1 (n = 27) received thymosin-alpha1 [1.6 mg subcutaneously (sc), twice a week] and interferon alpha-2b (10 MIU sc, three times per week) for 26 weeks, subsequently followed by interferon alpha-2b monotherapy at the same dosage for an additional 26 weeks. Group 2 (n = 10) received interferon alpha-2b (10 MIU sc, three times per week) for 52 weeks. Group 3 (n = 15) received interferon alpha-2b (10 MIU sc, three times per week) and lamivudine [100 mg orally (po), q.d.] for 52 weeks, followed by continuous lamivudine (100 mg po, q.d.) therapy. By the end of 78 weeks, a sustained response (SR-6 mo) was seen in 74% (20/27) of the patients within Group 1. On the contrary, Groups 2 and 3 had sustained response rates of 40 (4/10) and 53.3% (8/15), respectively (p = 0.13). At the end of 12 months post-treatment in Group 1, a virological and biochemical response rate was seen in 70.3% of patients (19/27); in contrast, Groups 2 and 3 had response rates of 20 (2/10) and 26.6% (4/15), respectively (p = 0036). At the end of the 18-month post-treatment follow-up period, 71.4% (19/27) of patients in Group 1, 10% of patients in Group 2 (1/10), and 20% of patients in Group 3(3/15) preserved their sustained response (p = 0.0003). Interferon alpha-2b and thymosin-alpha1 combination therapy results in significant virological and biochemical response rates compared with standard therapeutic regimens and is well tolerated.

Effects of albumin supplementation during cardioplegia administration: an in vitro analysis.

Increasing, the colloid osmotic pressure (COP) of blood cardioplegia (BCP) may reduce myocardial edema and preserve cardiac function following cardiopulmonary bypass (CPB). The purpose of this study was to quantify the effects of albumin (ALB) supplementation on cardioplegia COP through an in vitro analysis. A self-contained cardioplegia delivery system administered supplemental ALB to four BCP ratios (1:1, 4:1, 8:1, and 20:1). In Group A, 25% ALB was combined with BCP at four delivery rates (0, 13, 25, and 50 mL ALB/L BCP), with a delivery rate of 0 mL ALB/L BCP serving as the control for all groups. Twenty-five percent ALB was added to crystalloid to create carrier solutions containing 12.5, 25, or 50 g ALB/L in Group B, while Group C combined an ALB delivery rate of 50 mL ALB/L BCP with each of the three carrier solutions. End-points included initial and post-supplementation hematocrit, total serum protein (TSP), and COP. Without supplemental ALB, TSP was less affected with increasing blood to crystalloid ratios (1:1-81.7 +/- 6.2%, 4:1-40.6 +/- 5.1%, 8:1-20.6 +/- 4.1%, 20:1-6.0 +/- 5.7%). The TSP of 1:1 and 4:1 BCP increased (p < .0003 and p < .02) across all methods of supplementation, while 8:1 BCP was similarly increased (p < .008), except with 12.5 and 25 g ALB/L carrier solutions. The greatest change from baseline COP was seen with the lower blood to crystalloid ratios (1:1-64.3 +/- 5.0% and 4:1-39.5 +/- 10.5%). In higher ratios, the effects of dilution were less profound (14.6 +/- 4.2 +/- 4.2% and 20:1-6.0 +/- 1.9%). COP of 1:1 BCP increased (p < .008) whenever ALB was added. In conclusion, TSP and COP of blood cardioplegic solutions is increased by supplemental albumin administration with quantitative enhancement dependent upon the dilutional effects of the blood to crystalloid ratio.

A significant diffuse component predicts for inferior survival in grade 3 follicular lymphoma, but cytologic subtypes do not predict survival.

Grade 3 follicular lymphoma (FL3) is thought to have an aggressive clinical course. On the basis of possible biologic differences, the new World Health Organization (WHO) classification of lymphoma suggests further subdivision of FL3 into grades 3a and 3b and states that the percentage of involvement by diffuse large B-cell lymphoma (DLBCL) should also be reported. However, the clinical implications of these features are unclear. Therefore, we studied 190 newly diagnosed patients with lymph node-based FL3 who received anthracycline-containing combination chemotherapy. The follicular component was subclassified as grade 3a (FL3a) or grade 3b (FL3b) according to the WHO criteria, or as follicular large cleaved cell type (FLC). The percentage of a diffuse component, if present, was also recorded. Of the 190 cases, there were 107 FL3a (56%), 53 FL3b (28%), and 30 FLC (16%) cases. Diffuse areas were seen in 72 cases (31 FL3a, 28 FL3b, and 13 FLC). There were no significant differences in the clinical characteristics, overall survival, or event-free survival between patients with grades FL3a, FL3b, or FLC. However, those cases with a predominant diffuse component (> 50% diffuse) had a significantly worse overall survival (P =.0037) and event-free survival (P =.012). Therefore, we conclude that the subdivision of FL3 into cytologic subtypes does not appear to be important clinically. However, patients with FL3 having a diffuse component of more than 50% have an inferior survival that is similar to the survival of those with DLBCL.

Perfusion treatment algorithm: methods of improving the quality of perfusion.

The pathophysiological consequence associated with cardiopulmonary bypass (CPB) has generated a movement away from this technology in the treatment of heart disease. The negative outcomes are multifactorial in origin and may be associated both with the conduct of CPB and the instrumentation of extracorporeal flow. The purpose of this study was twofold. First, to develop a bedside patient risk assessment to aid in the development of a perfusion care plan. Second, to identify the controllable variables used during CPB that contribute to overall morbidity. Controllable perfusion-related variables that were positively linked to improved patient outcomes were identified from randomized, peer-reviewed human studies. Such variables as hematocrit, mean arterial pressure, thermic perfusion, blood lactate, colloid osmotic pressure, pulsatile perfusion, acid base homeostasis, oxygenation, and coated circuitry were included. Patient risk assessment was developed using the Society of Thoracic Surgeon database, where 61 variables affecting postoperative morbidity were identified. These variables were used to develop a bedside tool, Mortality Assessment Perfusion Score (MAPS), to guide the perfusion patient care plan. The MAPS generates a specific value that may predict patient morbidity and mortality based on past mortalities. In conclusion, the improvement in patient outcome may be associated with both the change in conduct of CPB and the quantitative assessment of patient risk stratification and a patient treatment algorithm.

The effects of aprotinin on platelet function in blood exposed to eptifibatide: an in vitro analysis.

The preoperative use of platelet inhibitors has increased the risk of bleeding during cardiac surgery. Aprotinin has been shown to preserve hemostatic function in patients undergoing CPB. The purpose of this study was to investigate the effect of aprotinin on coagulation in blood exposed to eptifibatide. Freshly collected bovine blood was used in an in vitro model of extracorporeal circulation. Blood was separated into two groups: activated (60 minutes exposure to bubble oxygenation) and nonactivated. Within each group there were four subgroups: control (n = 3), eptifibatide (2.8 microg/mL, n = 3), aprotinin (250 KIU/mL, n = 3), and eptifibatide with aprotinin (2.8 microg/mL, 250 KIU/mL, n = 3). Twenty-four modified extracorporeal circuits utilizing a hard-shell venous reservoir and cardioplegia heat exchangers were used. Blood flow was maintained at a rate of 1.25 L/min for a total of 170 minutes, at 37 +/- 1 degree C. Samples were collected at 0, 20, 50, and 110 minutes with the following variables measured: thromboelastograph (TEG), activated clotting time (ACT), and hematocrit (Hct). Results demonstrated that at 110 minutes, the TEG index (TI) was decreased by four-fold in the activated group compared to the nonactivated group (-4.6 +/- 1.2 vs. 1.4 +/- 1.5, p < .05). The administration of aprotinin resulted in preservation of the TI as compared to eptifibatide-treated blood (-4.9 +/- 1.2 vs. -7.9 +/- 1.2, p < .05). Aprotinin combined with eptifibatide reduced coagulation derangements when compared to eptifibatide alone (-5.2 +/- 1.2 vs. -7.9 +/- 1.2, p < .05). In conclusion, aprotinin attenuated the platelet inhibition effect of eptifibatide during in vitro CPB, resulting in improved coagulation.

The effect of electrolyte imbalance on weaning from cardiopulmonary bypass: an experimental study.

An imbalance in electrolyte concentration during separation from cardiopulmonary bypass (CPB) may lead to a disruption in excitation-contraction coupling resulting in a failure to wean. The etiology of myocardial dysfunction is multifactorial, and includes alterations in acid-base balance, glucose metabolism, and cellular function. The purpose of this study was to assess the effect of hyperkalemia on myocardial function during separation from CPB. A porcine model (n = 5) of hypothermic (32 degrees C) CPB was used where hyperkalemia [K+ (6.5 +/- 1.0)] was created before weaning. A 3-minute weaning process was initiated once normothermia was achieved. Mixed venous and arterial samples were obtained during CPB, weaning, and 10 minutes postbypass. Samples were assayed for [K+], [Ca++], glucose, pH, CPK-MB, and lactic acid levels. Hyperkalemia resulted in the generation of severe arrhythmias in all animals. During the immediate prewean period, there was a significant correlation between venous [K+] and pH (p < .01, r2 =.891). Arterial pH did not change during the weaning or post-CPB period, while venous pH declined significantly throughout the same period (7.35 +/- 0.75 to 7.20 +/- 0.17, p < .05). No other measured variables correlated with hyperkalemia. In summary, hyperkalemia caused a significant decline in venous pH evidenced in the early separation period, but had no effect on other variables. Therefore, measurement of venous pH may be an early marker indicating myocardial dysfunction and dysrhythmia.

Increasing incidence of all stages of kidney cancer in the last 2 decades in the United States: an analysis of surveillance, epidemiology and end results program data.

PURPOSE: Since the 1980s with the increased use of abdominal imaging, such as computerized abdominal tomography, renal cancer has commonly been diagnosed as an incidental mass. We analyzed the renal cancer incidence from 1973 to 1998 in the Surveillance, Epidemiology and End Results program by historic staging of localized, regional or distant disease to evaluate possible stage migration due to increased abdominal imaging. MATERIALS AND METHODS: We used renal cancer data from the Surveillance, Epidemiology and End Results 9 registries, public use, August 2000 submission (National Cancer Institute, Bethesda, Maryland), which represents approximately 14% of the United States population. We analyzed the age adjusted renal cancer incidence from 1973 to 1998 using the 1990 American standard million population. We compared the incidence of the 3 stages of renal cancer from 1973 to 1985 and 1986 to 1998 by the chi-square test and used joinpoint regression analysis to determine whether there was a significant change in the intragroup or intergroup incidence rate with time. RESULTS: During 1973 to 1985 the rate of localized, regional and distant renal cancer was 45%, 23% and 32% compared with 54%, 21% and 25%, respectively, from 1986 to 1998 (p = 0.45). However, the plot of incidence rate versus diagnosis year by stage showed an increasing trend in the 3 stage groups. The annual percent change in the localized, regional and distant groups was 3.7 (95% confidence interval [CI] 3.2 to 4.2), 1.9 (95% CI 1.2 to 2.6) and 0.68 (95% CI 0.1 to 1.3) per 100,000 population, respectively (p <0.05). The 3 groups also had significantly different growth rates (p <0.01). CONCLUSIONS: There was no significant difference in stage at presentation of renal cancer diagnosed in 1973 to 1985 compared with that diagnosed in 1986 to 1998. While the lack of a decrease in distant disease despite the increased detection of regional and localized renal cancer implies that a proportion of innocuous renal cancer cases may be detected by increased abdominal imaging, the increased incidence of renal cancer in all 3 categories indicates that other factors may also be contributing to the increasing incidence of renal cancer.

The effect of surface modification and aprotinin on cellular injury during simulated cardiopulmonary bypass.

Cardiopulmonary bypass (CPB) elicits derangements to the formed elements of blood because of the physical stresses of extracorporeal flow. Methods of reducing the impact of CPB include circuit surface modification and pharmacological supplementation. The purpose of this study was to examine the effects of aprotinin in combination with surface modification during simulated CPB. Fresh whole bovine blood was used to prime standard CPB circuits divided into four groups (N = 3): control (CTR), aprotinin 300 KIU/mL (APR), Poly (2-methoxyethylacrylate) coating (PMEA), and APR with PMEA (APR-PMEA). Physical stresses included venous reservoir negative pressure (-85 mmHg), arterial line pressure of 150 mmHg at 5 LPM, and air-blood interface, applied over a 90-minute period. Samples were drawn at the following times: 0, 10, 45, and 90 minutes. Endpoints included platelet count (PLT), plasma-free hemoglobin (PFHb), and thromboelastography (TEG). PLT did not change (138.9 +/- 15.0 vs. 102.9 +/- 21.0, p = ns) throughout the 90-minute experimental periods in any group. PFHb increased significantly (mean of 19- fold) throughout the experiment, but was not affected by any treatment. The TEG index declined in the CTR (3.6 +/- 0.4 vs. -16.2 +/- 2.9, p < .0003), PMEA (5.9 +/- 0.8 vs. -2.7 +/- 3.8, p < .02), and APR-PMEA (4.6 +/- 1.0 vs. -2.8 +/- 0.3 p < .0003) groups, but not in the APR group (3.6 +/- 2.2 vs. -1.3 +/- 3.3 p = .10). In conclusion, neither APR nor PMEA had an effect on either red cell hemolysis or PLT, but APR treatment alone significantly attenuated the derangements in coagulation induced in this extracorporeal model.