Clinical trial: 2-L polyethylene glycol-based lavage solutions for colonoscopy preparation - a randomized, single-blind study of two formulations.

BACKGROUND: The 2-L polyethylene glycol (PEG) lavage solutions provide efficacy similar to that of standard 4-L PEG formulations in spite of the reduced volume. The comparative efficacy and tolerability of two formulations of 2-L PEG solution remain unknown. AIMS: To assess the efficacy, safety and tolerability of PEG + Bis compared with PEG + Asc, and to study the effect of bowel cleansing quality on adenoma detection rates. METHODS: Patients were randomized to receive either 2-L PEG with ascorbic acid (PEG + Asc) or 2-L PEG plus bisacodyl 10 mg (PEG + Bis). The primary endpoint was overall colon cleansing score, assessed by blinded investigators using a validated four-point scale. Secondary endpoints included adenoma detection rate, patient tolerability and compliance and adverse events. RESULTS: Fifty-two patients received PEG + Asc and 55 patients received PEG + Bis. Overall colon cleansing scores (+/-s.d.) were 1.40 +/- 0.69 and 1.75 +/- 0.70 (P < 0.003) in the PEG + Asc and PEG + Bis groups, respectively. Excellent and good ratings were recorded in 69% and 23% receiving PEG + Asc compared to 38% and 51% (P = 0.01) of patients receiving PEG + Bis. More adenomas were detected in colonoscopies performed with PEG + Asc (39%) than in those performed with PEG + Bis (20%) (P = 0.04). Patient tolerability and safety were similar with both preparations. CONCLUSION: The use of PEG + Asc resulted in better colon cleansing and higher adenoma detection rates compared with PEG + Bis.

A randomized, placebo-controlled study of the effects of naproxen, aspirin, celecoxib or clopidogrel on gastroduodenal mucosal healing.

BACKGROUND: Many individuals with gastroduodenal ulcers require on-going, non-steroidal anti-inflammatory drug (NSAID) or anti-platelet therapy. AIMS: To evaluate the effects of these agents on gastroduodenal mucosal healing. METHODS: Helicobacter pylori-negative volunteers were randomized to receive naproxen, celecoxib, aspirin, clopidogrel or placebo. Antral and duodenal lesions were created endoscopically with a biopsy forceps. After 7 days of medication dosing, each lesion was scored [from 0 (low) to 8 (high)] using a validated methodology. The primary endpoint was the mean injury score. The secondary endpoint was the percentage of subjects with > or = 1 unhealed lesion. RESULTS: In all, 108 subjects completed the study. Naproxen impaired antral lesion healing more than placebo, clopidogrel, aspirin or celecoxib (mean injury score of 4.3 vs. 3.0, 2.7, 3.2, and 3.2, respectively, P < 0.05). Naproxen impaired duodenal lesion healing more than placebo, clopidogrel or aspirin (mean injury score of 4.0 vs. 2.4, 2.6, and 2.2, respectively, P < 0.05). More subjects taking naproxen than placebo or clopidogrel had > or =1 unhealed antral lesions (72.2% vs. 36.0% and 32.0%, respectively, P < 0.05) and unhealed duodenal lesions (61.1% vs. 16.0% and 28.0%, respectively, P < 0.05). CONCLUSIONS: Naproxen may impair gastroduodenal healing more than aspirin or celecoxib in H. pylori negative subjects. Clopidogrel did not impair mucosal healing.

Accurate method for clinical assessment of right lobe liver weight in adult living-related liver transplant.

INTRODUCTION: Prior to transplantation of segmental liver grafts to adult recipients, it is crucial to confirm that the graft size is safe for the donor, yet adequate for the recipient's metabolic needs. Computed tomography (CT) and magnetic resonance imaging (MRI) are the current best standards. We applied a new formula to estimate right liver lobe weight in living donors and compared our results with CT and MRI. METHODS: Between August 1998 and December 20, 91 adults received right lobes from living donors. Donor liver volumes were assessed by CT or MRI. Actual weights of right lobe grafts were determined after back table flushing. We estimated whole liver weights using the formula: 772 x body surface area (BSA). Right lobe liver weight was calculated as 57% of the estimated whole liver weight (R-57). RESULTS: Mean actual right lobe weight (n = 90) was 855.83 +/- 183.4 g. Estimated right lobe weight was 858.08 +/- 90.80 (R-57, P = NS); 1077.35 +/- 263.07 mL for CT (P = .0001), and 1185.07 +/- 350.10 mL for MRI (P = .0001). Mean graft-recipient weight ratio (GRWR) was 1.23%; there was no significant difference with R-57 GRWR but there was a difference from CT and MRI-GRWR (P = .001). The proportion of cases of estimated right lobe weight and GRWR within 20% of the corresponding actual value were 80% and 90%, respectively, for R-57 versus 36% and 43% for the imaging studies (P = .0001). CONCLUSION: With readily available software to calculate BSA, physicians can predict right lobe weight knowing only the donor's height and weight. CT and MRI will only be necessary for anatomic liver mapping.

Changes in regional cerebral blood flow under hypothermic selective cerebral perfusion.

OBJECTIVE: Currently the most frequently used perfusion technique during aortic arch surgery to prevent cerebral damage is hypothermic selective cerebral perfusion (SCP). Changes in cerebral blood flow (CBF) are known to occur during these procedures. We investigated regional changes of CBF under conditions of SCP in a porcine model. METHODS: In this blinded study, twenty-three juvenile pigs (20 - 22 kg) were randomized after cooling to 20 degrees C on CPB. Group I (n = 12) underwent SCP for 90 minutes, while group II (n = 11) underwent total body perfusion. Fluorescent microspheres were injected at seven time-points to calculate total and regional CBF. Hemodynamics, intracranial pressure (ICP), cerebrovascular resistance (CVR) and oxygen consumption were assessed. Tissue samples from the neocortex, cerebellum, hippocampus and brain stem were taken for a microsphere count. RESULTS: CBF decreased significantly (p = 0.0001) during cooling, but remained at significantly higher levels with SCP than with CPB throughout perfusion (p < 0.0001) and recovery (p < 0.0001). These findings were similar among all regions of the brain, certainly at different levels. Neocortex CBF decreased 50%, whereas brain stem and hippocampus CBF decreased by only 25 % during total body perfusion. All four regions showed 10 - 20% less CBF in the post-CPB period. CBF during SCP did not fall by more than 20% in any analysed region. The hippocampus turned out to have the lowest CBF, while the neocortex showed the highest CBF. CONCLUSION: SCP improves CBF in all regions of the brain. Our study characterizes the brain specific hierarchy of blood flow during SCP and total body perfusion. These dynamics are highly relevant for clinical strategies of perfusion.

A simple new formula to assess liver weight.

INTRODUCTION: In cadaveric or segmental liver transplantation, accurate assessment of graft volume is desirable but not always easy to achieve based on donor morphometric data. We sought to establish a simple, reliable formula for accurate prediction of liver volume. METHODS: Data from 1,413 cadaveric adult and pediatric liver donors were analyzed using simple and multiple regression analysis. Liver weight (LW) was plotted against age, height, body weight (BW), body surface area (BSA) or body mass index (BMI); a formula was developed using simple regression: LW (g) = 772 (g/m(2)) x BSA, r = 0.73, P <.01. For donors with BSA 1.0, there was no significant difference between the actual and the estimated mean LW as calculated by the new formula. For pediatric donors, there was no significant difference between estimated and actual mean liver weight with any formula. When the new formula was applied, the difference between the actual and the estimated liver weight was acceptable (<20%) in 1040 (73.6%) cases. In all races, there was no significant difference between actual and estimated mean liver weight as calculated by this formula. CONCLUSIONS: A simple formula to calculate liver weight in donors with BSA >1.0 is: LW = 772 x BSA, and for donors with BSA

Surgery for late-onset ulcerative colitis: predictors of short-term outcome.

BACKGROUND: Onset of ulcerative colitis and Crohn disease after the age of 65 (late-onset disease) is not common, and is usually associated with a worse prognosis. We review our experience with late-onset ulcerative colitis and define the predictors of short-term outcome. METHODS: A retrospective analysis of our surgical experience with 33 patients suffering from late-onset ulcerative colitis. The medical records of 17 women and 16 men who had surgery between 1984 and 1999 were reviewed for age at surgery, sex, duration of disease, extent of disease, indications for surgery, surgical procedures and outcome. Additionally, we identified predictors of outcome. RESULTS: The median age at surgery was 74 years (range 65-83). The most common indication for surgery was refractoriness to medical treatment. There were 4 deaths for a mortality rate of 12%, and 7 major complications. There was no mortality for elective procedures. On univariate analysis, albumin levels of 2.8 g/dl or less and urgent surgery were predictors of poor outcome. Disease of short duration (3 years or less from onset of disease to surgery) was also associated with a poor outcome, but this did not reach statistical significance. CONCLUSIONS: We conclude that in the elderly population suffering from late-onset ulcerative colitis and requiring an operation, urgent surgery and hypoalbuminemia are predictors of adverse outcome. Age at surgery, sex and the extent of colonic involvement did not influence outcome. Low complication and death rates should be expected for elective procedures in the elderly.

Surgery for ulcerative colitis in elderly persons: changes in indications for surgery and outcome over time.

HYPOTHESIS: Medical therapy has changed the indications for surgery over the last 4 decades. Advances in perioperative care have significantly improved the outcome. DESIGN: The medical records of all patients 65 years and older who underwent surgery for ulcerative colitis during a 40-year period were analyzed retrospectively. SETTING: Tertiary referral center. PATIENTS: One hundred thirteen consecutive patients 65 years and older who underwent surgery for ulcerative colitis between January 1, 1960, and June 30, 1999. MAIN OUTCOME MEASURES: Changes in elective and urgent indications for surgery. Changes over time in outcome and the factors that brought about these changes. Predictors of poor outcome in an elderly population with ulcerative colitis. RESULTS: One hundred thirteen patients were divided into 3 cohorts of 38, 38, and 37 consecutive patients admitted to the hospital during the periods 1960 through 1984, 1985 through 1993, and 1994 through 1999, respectively. Indications for surgery and morbidity and mortality rates have changed with time. Dysplasia has replaced carcinoma as a major indication for elective surgery (P =.001). Toxic megacolon has become significantly less common as an indication for urgent surgery (P =.001). Surgery-associated adverse outcomes have decreased significantly from 50% (13% deaths, 37% major complications) to 27% (3% deaths, 24% major complications) (P =.04). Male sex, an albumin level of 2.8 g/dL or less, and urgent surgery were found to be independent predictors of poor outcome. CONCLUSIONS: In our referral center, the indications for urgent and elective surgery have changed during the past 4 decades from toxic megacolon and carcinoma, to disease refractory, to medical therapy and dysplasia, respectively. Morbidity and mortality have decreased dramatically over time. Urgent procedures, low levels of albumin, and male sex are all predictors of poor outcome.

The visual analog scale for pain: clinical significance in postoperative patients.

BACKGROUND: The visual analog scale is widely used in research studies, but its connection with clinical experience outside the research setting and the best way to administer the VAS forms are not well established. This study defines changes in dosing of intravenous patient-controlled analgesia as a clinically relevant outcome and compares it with VAS measures of postoperative pain. METHODS: Visual analog scale measurements were obtained from 150 patients on the morning after intraabdominal surgery. On the same afternoon, 50 of the patients provided a VAS score on the same form used in the morning, 50 on a new form, and 50 were not asked for a second VAS measurement. RESULTS: Visual analog scale values and changes in value were similar for patients who were given a new VAS form in the afternoon and those who used the form that showed the morning value. The proportions of patients requesting additional analgesia were 4, 43, and 80%, corresponding to afternoon VAS scores of 30 or less, 31-70, and greater than 70, respectively. Change from morning VAS score had no apparent influence on patient-controlled analgesic dosing for patients with afternoon values of 30 or less or greater than 70, but changes in VAS scores of at least 10 did discriminate among patients whose afternoon values were between 31 and 70. CONCLUSIONS: When pain is an outcome measure in research studies, grouping final VAS scores into a small number of categories provides greater clinical relevance for comparisons than using the full spectrum of measured values or changes in value. Seeing an earlier VAS form has no apparent influence on later values.

Critical graft size in adult-to-adult living donor liver transplantation: impact of the recipient's disease.

The aim of this study is to analyze the impact of the recipient's disease severity on graft size requirements and outcome in adult-to-adult living donor liver transplantation. A limiting factor in adult-to-adult living donor liver transplantation has been adequacy of graft size. A minimal graft-recipient weight ratio (GRWR) of 0.8% to 1% has been suggested, without taking the recipient's disease into account. Forty adults underwent liver transplantation using left (n = 10; mean weight, 481 +/- 83 g) or right lobes (n = 30; mean weight, 845 +/- 182 g). We recorded graft survival, Child-Turcotte-Pugh score, and occurrence of small-for-size syndrome (poor bile production, prolonged postoperative prothrombin time, and cholestasis without ischemia markers). Small grafts were defined as GRWR of < or =0.85%. Large grafts were defined as GRWR greater than 0.85%. Six patients died within 6 months of transplantation (early patient survival rate, 85%); two patients died late of tumor recurrence. Among transplant recipients with normal liver function or Child's class A, there was no significant difference with the use of small (n = 6) or large (n = 9) grafts (graft survival rates, 83% v 88%, respectively; P =.65). Among patients with Child's class B or C, graft survival rates were 74% in recipients of large grafts (n = 19) and 33% in recipients of small grafts (n = 6; P =.023). Five of 6 patients with Child's class B or C who received small grafts developed small-for-size syndrome; 2 patients died (1 patient after retransplantation) and 3 patients survived (2 patients after retransplantation). Graft function and survival are influenced not only by graft size, but also by pretransplantation disease severity. GRWR as low as 0.6% can be used safely in patients without cirrhosis or in patients with Child's class A. Transplant recipients with Child's class B or C require a GRWR greater than 0.85% to avoid small-for-size syndrome and related complications.

Cytotoxic T-lymphocyte antigen 4 gene polymorphisms and susceptibility to acute allograft rejection.

BACKGROUND: Cytotoxic T-lymphocyte antigen 4 (CTLA4) has been shown to play a critical role in the down-regulation of the immune response. We retrospectively examined the association between acute rejection and two polymorphisms in the CTLA4 gene, the dinucleotide (AT)n repeat polymorphism in exon 3 and the single nucleotide polymorphism A/G at position 49 in exon 1, in a cohort of liver and kidney transplant recipients. METHODS AND RESULTS: A total of 207 liver and 167 renal transplant recipients were analyzed. In the case of the (AT)n repeat polymorphism we found an increased incidence of acute rejection in association with allele 3 and 4 in both liver and kidney (P=0.002 and 0.05, respectively). In addition, in liver transplant recipients, allele 7 was associated with acute rejection independent of ethnicity (P<0.05). Allele 1 was less frequently observed in African American as compared with Caucasian liver and kidney transplant recipients, with a frequency of 33.8% and 69%, respectively (P<0.0001). Those patients with allele 1 had a tendency toward a lower rate of rejection at 42% versus 57.8% (P=0.058), suggesting a potential protective effect of allele 1. Analysis of the A/G single nucleotide polymorphism demonstrated no association between either allele and the incidence of acute rejection in the patients studied. CONCLUSION: These initial observations provide the necessary basis to further investigate the risk stratification of transplant recipients based on specific CTLA4 gene polymorphisms.

Use of intraoperative transesophageal echocardiography to predict atrial fibrillation after coronary artery bypass grafting.

BACKGROUND: Postoperative atrial fibrillation in coronary artery bypass graft surgery occurs in 10-40% of patients. It is associated with a significant degree of morbidity and results in prolonged lengths of stay in both the intensive care unit and hospital. METHODS: The authors prospectively evaluated patients undergoing coronary artery bypass with detailed transesophageal echocardiography examinations conducted before and after cardiopulmonary bypass to study whether risk factors for atrial fibrillation could be identified. Demographic and surgical parameters were also included in the analysis. Selected variables were subjected to univariate and subsequent multivariate analyses to test for their independent or joint influence on atrial fibrillation. RESULTS: Seventy-nine patients had assessable transesophageal echocardiography examinations. Significant univariate predictors of atrial fibrillation included advanced age (P = 0.002), pre-cardiopulmonary bypass left atrial appendage area (P = 0.04), and post-cardiopulmonary bypass left upper pulmonary vein systole/diastole velocity ratio (P = 0.03). When these three factors were considered together in a multiple logistic regression analysis, left upper pulmonary vein systole/diastole velocity ratio was a significant predictor (P < 0.05), as was the joint effect of age plus pre-cardiopulmonary bypass left atrial appendage area (P = 0.005). The probability of developing atrial fibrillation for the combination of age = 75 yr, post-cardiopulmonary bypass left upper pulmonary vein systole/diastole velocity ratio = 0.5, and left atrial appendage area = 4.0 cm was 0.83 (95% confidence interval, 0.51-0.96). CONCLUSIONS: Early identification of patients at risk for postoperative atrial fibrillation may be feasible using the parameters identified in this study.

Endotoxin-neutralizing capacity of serum from cardiac surgical patients.

OBJECTIVE: To determine if endotoxin core antibody (EndoCAb) from the serum of cardiac surgical patients neutralizes endotoxin in an ex vivo biologic assay. DESIGN: Prospective blinded cohort study. SETTING: Academic medical center. PARTICIPANTS: Patients (n = 203) undergoing cardiac surgery. INTERVENTIONS: Sera were obtained from patients preoperatively. MEASUREMENTS AND MAIN RESULTS: EndoCAb levels were determined by enzyme-linked immunosorbent assay. Sera were incubated for 15 minutes at 37 degrees C with varying concentrations of endotoxin from a clinically relevant bacterium (Escherichia coli serotype O18), then tested for the presence of endotoxin activity using the validated Limulus amebocyte lysate assay. Median (interquartile range) IgM and IgG EndoCAb levels were 118 median units (range, 31 to 259 median units) and 208 median units (range, 108 to 401 medium units). Increasing levels of IgM EndoCAb were associated with increased neutralization of endotoxin (p < 0.0001). Increasing levels of IgG EndoCAb were associated with increased neutralization of endotoxin (p < 0.0001). An additive effect of IgM and IgG EndoCAb levels on endotoxin neutralization was observed without evidence of synergistic or plateau effects. EndoCAb levels did not completely predict serum neutralization capacity. CONCLUSION: Anti-EndoCAbs of both classes (IgM and IgG) were able to neutralize lipopolysaccharide from a clinically relevant bacterium in an ex vivo model. Neither Igm nor IgG appeared to be more capable of neutralization in this model. These antibodies did not completely predict neutralization capacity; other endogenous factors in human serum must be capable of lipopolysaccharide neutralization.

Retrograde cerebral perfusion provides negligible flow through brain capillaries in the pig.

OBJECTIVES: Although retrograde cerebral perfusion is being used clinically during aortic arch surgery, whether retrograde flow perfuses the brain effectively is still uncertain. METHODS: Fourteen pigs were cooled to 20 degrees C with cardiopulmonary bypass and perfused retrogradely via the superior vena cava for 30 minutes: 7 underwent standard retrograde cerebral perfusion and 7 underwent retrograde perfusion with occlusion of the inferior vena cava. Antegrade and retrograde cerebral blood flow were calculated by quantitating fluorescent microspheres trapped in brain tissue after the animals were put to death; microspheres returning to the aortic arch, the inferior vena cava, and the descending aorta were also analyzed during retrograde cerebral perfusion. RESULTS: Antegrade cerebral blood flow was 16 +/- 7.7 mL. min(-1). 100 g(-1) before retrograde cerebral perfusion and 22 +/- 6.3 mL. min(-1). 100 g(-1) before perfusion with caval occlusion (P =.14). During retrograde perfusion, calculations based on the number of microspheres trapped in the brain showed negligible flows (0.02 +/- 0.02 mL. min(-1). 100 g(-1) with retrograde cerebral perfusion and 0.04 +/- 0.02 mL. min(-1). 100 g(-1) with perfusion with caval occlusion; P =.09): only 0.01% and 0.02% of superior vena caval inflow, respectively. Less than 13% of retrograde superior vena caval inflow blood returned to the aortic arch with either technique. During retrograde cerebral perfusion, more than 90% of superior vena caval input was shunted to the inferior vena cava and was then recirculated, as indicated by rapid development of an equilibrium in microspheres between the superior and inferior venae cavae. With retrograde perfusion and inferior vena caval occlusion, less than 12% of inflow returned to the descending aorta and only 0.01% of microspheres. CONCLUSIONS: The paucity of microspheres trapped within the brain indicates that retrograde cerebral perfusion, either alone or combined with inferior vena caval occlusion, does not provide sufficient cerebral capillary perfusion to confer any metabolic benefit. The slightly improved outcome previously reported with retrograde cerebral perfusion during prolonged circulatory arrest in this model may be a consequence of enhanced cooling resulting from perfusion of nonbrain capillaries and from venoarterial and venovenous shunting.

Human leukocyte antigens (HLA)-Cw as prognostic indicators in autologous transplantation for lymphoma.

The human leukocyte antigens (HLA) function as transplantation antigens and as markers in disease association. Disparity at the HLA A, B, Cw, and DR loci in allogeneic stem cell transplants results in an increased incidence of graft-versus-host disease, graft rejection, and decreased survival. HLA class I loci A, B, and Cw also function as ligands for natural killer (NK) cell receptors in an interaction that predominantly inhibits cytolysis of target antigens. This HLA-NK cell inhibitory function is required for protection against auto-aggression, and is of unclear significance in other clinical settings. Furthermore, the prevention of auto-aggression is HLA molecule specific as demonstrated by the association of specific HLA types with autoimmune diseases. It is not known whether the HLA molecules might serve as markers for outcome in autologous transplants. We investigated an association of HLA class I molecules and early transplant outcome in a cohort of patients who underwent autologous transplantation for the treatment of lymphoma. In this retrospective study, HLA class I molecules were analyzed to determine whether they affect transplant outcome. HLA typing was performed by microlymphocytotoxicity assays. Factors such as age, sex, disease type, lactate dehydrogenase (LDH), cell dose, type of graft, and transfusion events were reviewed. Outcome was defined as death (or survival) at 6 months from the date of transplant. HLA-Cw8 was significantly associated with poor outcome (odds ratio = 18 and 9.3, p = 0.01 and 0.02 in homozygous and all patients, respectively). The HLA-A and B locus molecules were not associated with outcome. Age, sex, elevated LDH, and cell dose were not associated with outcome. A blood progenitor cell dose of greater than 6 x 10(8) nucleated cells/kg was favorably associated with outcome (p = 0.08). The number of transfusions received was not associated with outcome. In the multivariate analysis of HLAs and factors associated with outcome, HLA-Cw8 emerged as an independent risk factor for poor outcome (p = 0.03) following autologous transplantation in lymphoma patients. The association of HLA-Cw molecules with outcome in this study group indicates a need for further investigation of the HLA-mediated interactions that affect antitumor cytotoxicity, cytokine release, and regimen related toxicity.

Decreased endotoxin immunity is associated with greater mortality and/or prolonged hospitalization after surgery.

BACKGROUND: Patients undergoing noncardiac surgery often develop postoperative morbidity, potentially attributable to endotoxemia and the systemic inflammatory response syndrome. Endogenous antibodies to endotoxin may confer protection from endotoxin-mediated toxicity. The authors sought to determine the association of preoperative antiendotoxin immunity and death or prolonged hospitalization in a broad population of general surgical patients undergoing major surgery. METHODS: To test the hypothesis that low preoperative serum antiendotoxin core antibody (EndoCAb) concentration is an independent predictor of adverse outcome after general surgery, 1,056 patients undergoing routine noncardiac surgery were enrolled into a prospective, blinded, cohort study. Immunoglobulin M EndoCAb, immunoglobulin G EndoCAb, total inmunoglobulin M, and immunoglobulin G concentrations were measured in serum obtained preoperatively. A physiologic risk score using the established POSSUM criteria was assigned preoperatively to each patient. The primary predefined composite end point (postoperative complication) was either in-hospital death or postoperative length of stay greater than 10 days. Multivariate logistic regression was used to test the study hypothesis. RESULTS: Overall, postoperative complication occurred in 234 of the 1,056 patients (22.1%). Lower immunoglobulin M EndoCAb concentration (P = 0.006) predicted increased risk of postoperative complication independent of POSSUM physiologic risk score (P < 0.001). In contrast, total immunoglobulin M and total immunoglobulin G concentrations did not predict adverse outcome. Complications involved multiple organ systems and were generally unrelated to the type or site of surgery, consistent with the systemic inflammatory response syndrome. CONCLUSIONS: Adverse outcome after routine noncardiac surgery is common and is predicted in part by low concentrations of EndoCAb. The authors' findings suggest that endotoxemia may be a cause of postoperative morbidity after routine noncardiac surgery.

Long-term low-dose IL-2 enhances immune function in common variable immunodeficiency.

Common variable immunodeficiency (CVID) is a primary immunodeficiency disease characterized by hypogammaglobulinemia and lack of antibody production. Numerous T cell defects have been described, including reduced gene expression and production of IL-2. Since some of the T cell defects could be explained by lack of IL-2, we have been investigating the effects of in vivo IL-2 treatment. Here, a long-acting form of IL-2, PEG-IL-2, was given for 12-18 months to 15 randomly chosen CVID subjects, in comparison to 39 CVID subjects who served as controls. After 6 to 12 months of treatment, T cell proliferative responses to mitogens and to IL-2 were significantly enhanced; proliferative responses to tetanus and candida antigens increased up to 50-fold. Four of eight subjects immunized with the neoantigen bacteriophage φX 174 displayed increased antibody responses after treatment. Treated subjects recorded reduced, but not overall statistically significant, days of bronchitis, diarrhea, and joint pain. These data indicate that IL-2 might serve as an adjuvant to therapy in some subjects with CVID, enhancing T cell functions and reversing T cell anergy in most.

The influence of acute rejection on long-term renal allograft survival: a comparison of living and cadaveric donor transplantation.

BACKGROUND: We investigated whether recipients of living donor grafts who suffer an acute rejection progress to graft loss because of chronic rejection at a slower rate than recipients of cadaveric grafts. METHODS: A retrospective review was made of 296 renal transplantations performed at Mount Sinai Hospital. Only grafts functioning for at least 3 months were included in this analysis. Demographic variables of donor and recipient age, race, sex, and serum creatinine at 3 months after transplantation were compared between groups. RESULTS: Among the acute rejection-free cohort, the estimated 5-year graft survival was 90% for those receiving transplants from living relatives and 88% for those receiving cadaveric transplants (P=0.76). However, in grafts with early acute rejection, the 5-year survival was 40% for cadaveric recipients compared with 73% for living related graft recipients (P<0.014). Using the proportional hazards model, cadaveric donor source, older donor age, African American recipient race, and elevated 3-month serum creatinine were independent predictors of long-term graft loss caused by chronic rejection. The severity of acute rejection and recipient age had no impact on the risk of graft loss because of chronic rejection. CONCLUSION: These data indicate that the benefit of living related transplantation results from the fact that a living related graft progresses from acute to chronic rejection at a slower rate than a cadaveric graft. Furthermore, a cadaveric graft that is free of acute rejection 3 months after transplantation has an equal likelihood of functioning at 5 years as that of a graft from a living related donor.

Seroprevalence of Helicobacter pylori infection in patients with lymphoma.

To determine the Helicobacter pylori (HP) seroprevalence in patients with non-Hodgkin's lymphoma (NHL) and other hematological conditions. Sera were collected from 444 patients with NHL, Hodgkin's disease (HD), lymphoproliferative disorders (LPD), myeloproliferative disorders (MPD), and other hematological conditions. HP seropositivity was determined by ELISA and the results were compared among diagnostic groups HP seropositivity was observed in 168/444 (38%) of the total population. Higher seropositivity rates were associated with increasing age (p=0.001), and country of birth outside the USA and Canada (p=0.0001). Among the diagnostic groups, patients with NHL demonstrated the highest frequency (43%) and those with HD, the lowest frequency (20%; p=.026) of HP seropositivity. The differences among diagnostic groups remained statistically significant after controlling for country of birth (p<0.05), but not after controlling for patient age at diagnosis. The HP seroprevalence of G1 NHL was 55% compared to 40% for non-G1 NHL (p=NS). The highest rate of HP seropositivity (67%) occurred in gastric MALT lymphoma patients, although this did not reach statistical significance compared to the non MALT group (50%) due to small sample size. In conclusion, the rate of HP seropositivity in patients with MALT lymphoma in the USA appears to be lower than in Europe. Helicobacter pylori does not appear to be an important factor in other types of NHL of the G1 tract or elsewhere. Studies of HP prevalence should be controlled for country of birth as well as for age.

Neurologic outcome after ascending aorta-aortic arch operations: effect of brain protection technique in high-risk patients.

OBJECTIVE: We sought to assess the optimal strategy for avoiding neurologic injury after aortic operations requiring hypothermic circulatory arrest. METHODS: All 717 patients who survived ascending aorta-aortic arch operations through a median sternotomy since 1986 were examined for factors influencing stroke. Temporary neurologic dysfunction was assessed in all patients who survived the operation without stroke since 1993. Multivariate analyses were carried out to determine independent risk factors for neurologic injury. RESULTS: Independent risk factors for stroke were as follows: age greater than 60 years (P <.001; odds ratio, 4.5); emergency operation (P =.02; odds ratio, 2.2); new preoperative neurologic symptoms (P =.05; odds ratio, 2.9); presence of clot or atheroma (P <.001; odds ratio, 4.4); mitral valve replacement or other concomitant procedures (P =.055; odds ratio, = 3.7); and total cerebral protection time, defined as the sum of hypothermic circulatory arrest and any retrograde or antegrade cerebral perfusion (P =.001; odds ratio, 1.02/min). In 453 patients surviving operations without stroke after 1993, independent risk factors for temporary neurologic dysfunction included age (P <.001; odds ratio, 1.06/y), dissection (P =.001; odds ratio, 2.2), need for coronary artery bypass grafting (P =.006; odds ratio, 2.1) or other procedures (P =.023; odds ratio, 3.4), and total cerebral protection time (P <.001; odds ratio, 1.02/min). When all patients with total cerebral protection times between 40 and 80 minutes were examined, the method of cerebral protection did not influence the occurrence of stroke, but antegrade cerebral perfusion resulted in a significant reduction in incidence on temporary neurologic dysfunction (P =.05; odds ratio, 0.3). CONCLUSIONS: The occurrence of stroke is principally determined by patient- and disease-related factors, but use of antegrade cerebral perfusion can significantly reduce the occurrence of temporary neurologic dysfunction.

Favorable outcome after composite valve-graft replacement in patients older than 65 years.

BACKGROUND: Concomitant surgical replacement of the aortic valve and ascending aorta is an ideal treatment for aortic root aneurysms, but there may be hesitation in its use in older patients, despite their known increased risk of rupture. This study was conducted to examine our results in 84 patients older than 65 years undergoing elective aortic root resection with composite valve-graft replacement. METHODS: Eighty-four patients older than 65 years were operated on between June 1987 and August 1998. Median age was 74 years (range, 66 to 89 years), and 57 patients were men. Seventeen patients were undergoing reoperation. Aortic insufficiency was present in 70 patients. Forty-seven patients received a conduit using a bioprosthesis, whereas in 37 a mechanical valved conduit (St. Jude) was used. The ascending aorta alone was replaced in 23 patients; 50 had hemi-arch replacement, and in 11 the entire aortic arch was replaced. RESULTS: Hospital mortality was 8.3% (7 of 84). Sixteen late deaths (19%) were noted during a median follow-up of 3.2 years (range, 0 to 10 years). Only one late death was aorta-related. The incidence of thrombotic or hemorrhagic complications was 2.1/100 patient-years, with equal frequency for both mechanical and bioprosthetic valves. CONCLUSIONS: We conclude that composite valve-graft replacement in elderly patients results in a low operative mortality, yields excellent long-term survival, and averts fatal aneurysm rupture in this high-risk population.