Abnormalities in myelopoietic regulatory interactions with acidic isoferritins and lactoferrin in mice infected with Friend virus complex: association with altered expression of Ia antigens on effector and responding cells

The regulation of myelopoiesis was evaluated in B6D2F1 mice inoculated with Friend virus complex (spleen focus-forming virus plus helper virus) or helper virus alone by analyzing acidic isoferritin (AIF) and lactoferrin (LF) interactions with target cells. Under normal conditions, AIF suppresses colony and cluster formation by an Ia- antigen-positive cycling subpopulation of mouse granulocyte-macrophage progenitor cells (CFU-GM). Under the same conditions, the release of AIF-inhibitory activity and granulocyte-macrophage colony stimulatory factors (GM-CSF) from an Ia-antigen-positive subpopulation of monocytes and macrophages is suppressed by LF. Within one to two days after inoculation in vivo with Friend virus complex or helper virus, mouse CFU-GM become insensitive in vitro to suppression by purified human AIF as well as crude mouse AIF, and by four days, bone marrow, spleen, and thymus cells of these mice release much greater quantities of AIF- inhibitory activity than the cells from mice injected with control medium. The Friend virus complex itself has no influence in vitro on CFU-GM from normal mice. In addition, the release of AIF-inhibitory activity from bone marrow, spleen, and resident peritoneal cells and the release of GM-CSF from resident peritoneal cells of mice infected with Friend virus complex are not suppressed by LF. The inability of AIF to suppress colony formation by bone marrow and spleen CFU-GM from mice infected with Friend virus complex is associated with the loss of Ia (I-A subregion) antigens from CFU-GM, even though CFU-GM are in cycle. The nonresponsiveness of bone marrow, spleen, and peritoneal cells from these mice to LF suppression of AIF release and the inability of LF to influence GM-CSF release from peritoneal cells is associated with loss of Ia antigens from these cells. The above abnormalities are similar to the defects noted using cells from patients with leukemia. These results suggest that mice infected with Friend virus complex can serve as a model for investigating abnormalities in cell regulation and their relationships to disease progression.     

Assessment of Hageman factor activation in human plasma: quantification of activated Hageman factor-C1 inactivator complexes by an enzyme- linked differential antibody immunosorbent assay

An enzyme-linked immunosorbent assay has been developed for the quantitation of activated Hageman factor-C1 inactivator (HF-C1 INH) complexes. Addition of increasing quantities of either of the major forms of activated Hageman factor (HFa or HFf) to normal plasma or to Hageman factor-deficient plasma leads to a dose-dependent increase in activated HF-C1 INH complexes. As little as 0.5 micrograms/mL of activated HF added to plasma can be detected, corresponding to activation of approximately 2% of plasma HF. The sensitivity of the assay is increased at least tenfold when complexes are formed in HF- deficient plasma, indicating competition between unactivated HF and activated HF-C1 INH complexes for binding to the antibody. Specificity is demonstrated in that addition of activated HF to hereditary angioedema plasma yields less than 1% of the activated HF-C1 INH complex formation obtained with normal plasma. Kaolin activation of HF- deficient plasma yields no detectable complex formation. Kaolin activation of prekallikrein-deficient plasma demonstrates a time- dependent increase in formation of activated HF-C1 INH complex consistent with the ability of HF in this plasma to autoactivate as the time of incubation with the surface is increased. Kaolin treatment of high-molecular weight (HMW) kininogen-deficient plasma yields an even more profound abnormality in the rate of formation of activated HF-C1 INH complexes reflecting the complex role of HMW kininogen in the initiation of contact activation. Although addition of corn inhibitor to plasma prevents activated HF-C1 INH complex formation, it does not inhibit activated HF sufficiently fast to prevent prekallikrein activation.     

Current thinking on chronic renal allograft rejection: issues, concerns, and recommendations from a 1997 roundtable discussion

Chronic rejection accounts for most renal allograft losses after the first year posttransplantation. On March 24 and 25, 1997, a roundtable of five transplant surgeons, two nephrologists, and one pathologist assembled in Dallas, Texas, to review critical issues surrounding chronic renal allograft rejection. This article summarizes the presentations and relevant discussions of this meeting regarding the cause of chronic rejection, clinical diagnoses, risk factors, future prospects for intervention strategies, and general recommendations for the transplant community. Growing evidence indicates that chronic rejection is the aggregate sum of irreversible immunologic and nonimmunologic injuries to the renal graft over time. A history of acute rejection episodes and inadequate immunosuppression, likely attributable to inconsistent cyclosporine exposure or poor patient compliance, are among the most recognizable immunologic risk factors for chronic rejection. Donor organ quality, delayed graft function, and other donor and recipient variables leading to reduced nephron mass are nonimmunologic factors that contribute to the progressive deterioration of renal graft function. Clinical management of renal transplant recipients should incorporate both immunologic- and nonimmunologic-based intervention strategies aimed at minimizing risk factors to thwart the progression of chronic rejection and improve long-term allograft and patient survival.     

Re-assessing accumulated oxygen deficit in middle-distance runners

The purpose of this study was to re-assess the accumulated oxygen deficit (AOD), incorporating recent methodological improvements i.e., 4 min submaximal tests spread above and below the lactate threshold (LT). We Investigated the Influence of the VO2 -speed regression, on the precision of the estimated total energy demand and AOD. utilising different numbers of regression points and including measurement errors. Seven trained middle-distance runners (mean +/- SD age: 25.3 +/- 5.4y, mass: 73.7 +/- 4.3kg. VO2max 64.4 +/- 6.1 mL x kg(-1) x min(-1)) completed a VO2max, LT, 10 x 4 min exercise tests (above and below LT) and high-intensity exhaustive tests. The VO2 -speed regression was developed using 10 submaximal points and a forced y-intercept value. The average precision (measured as the width of 95% confidence Interval) for the estimated total energy demand using this regression was 7.8mL O2 Eq x kg(-1) x min(-1). There was a two-fold decrease in precision of estimated total energy demand with the Inclusion of measurement errors from the metabolic system. The mean AOD value was 43.3 mL O2 Eq x kg(-1) (upper and lower 95% CI 32.1 and 54.5mL o2 Eq x kg(-1) respectively). Converting the 95% CI for estimated total energy demand to AOD or including maximum possible measurement errors amplified the error associated with the estimated total energy demand. No significant difference in AOD variables were found, using 10,4 or 2 regression points with a forced y-intercept. For practical purposes we recommend the use of 4 submaximal values with a y-intercept. Using 95% CIs and calculating error highlighted possible error in estimating AOD. Without accurate data collection, increased variability could decrease the accuracy of the AOD as shown by a 95% CI of the AOD.     

Back to the Future: How Biology and Technology Could Change the Role of PTFE Grafts in Vascular Access Management

Although the arteriovenous fistula (AVF) is the preferred mode of dialysis vascular access, AVF maturation failure remains a huge clinical problem, often resulting in a prolonged duration of use of tunneled dialysis catheters. In contrast, polytetrafluoroethylene (PTFE) grafts do not suffer from early failure, but have significant problems with later stenosis and thrombosis. This review will initially summarize the pathology and pathogenesis of PTFE graft dysfunction and will then use this as a basis for describing some novel therapies, which may have the potential to reduce PTFE graft dysfunction. Finally, we will emphasize that the introduction of such therapies could be an important first step toward individualizing overall vascular access care.     

Laparoscopic radical nephrectomy for cancer with level I renal vein involvement

PURPOSE: Venous involvement develops in 5% to 10% of patients with renal cell carcinoma and is generally considered a relative contraindication to laparoscopic radical nephrectomy. To our knowledge we report the initial clinical series of laparoscopic radical nephrectomy for renal cell carcinoma associated with level I renal vein thrombus. MATERIALS AND METHODS: At our 2 institutions 8 patients each underwent laparoscopic radical nephrectomy for level I microscopic renal vein thrombus (group 1) and level I gross thrombus (group 2). In all 8 group 2 patients the level I thrombus was preoperatively diagnosed by computerized tomography. Mean renal tumor size in groups 1 and 2 was 7.8 and 12.4 cm., respectively. After controlling the renal artery the renal vein was secured by firing an endoscopic gastrointestinal anastomosis stapler on its collapsed, uninvolved proximal part adjacent to the vena cava. Intraoperative, postoperative and pathological parameters were assessed in the 2 groups. RESULTS: In group 1 laparoscopic radical nephrectomy was technically successful in all 8 patients. Mean operative time was 3.1 hours, mean estimated blood loss was 382 cc and mean hospital stay was 1.9 days. In 1 patient each a soft tissue and a vascular margin was positive for cancer. At a mean follow up of 19.5 months (range 2 to 36) metastatic disease occurred in 3 cases (38%). In group 2 laparoscopic radical nephrectomy was technically successful in 7 cases with open conversion in 1. Mean operative time was 3.3 hours, mean estimated blood loss was 354 cc and mean hospital stay was 2.3 days. Surgical soft tissue and the renal vein vascular margin of the transected vein were negative for cancer in all 8 cases. At a mean followup of 9.4 months (range 5 to 16) pulmonary metastasis developed in 1 patient (13%). CONCLUSIONS: Although it is an advanced procedure, laparoscopic radical nephrectomy in patients with level I renal vein thrombus is feasible, safe and follows established oncological principles.     

Evaluation of efficacy of four laparoscopic needle drivers.

INTRODUCTION: To evaluate the impact of needle driver design on laparoscopic suturing skills by experts and novices. METHODS: Three experienced laparoscopic surgeons and 3 novice junior residents were asked to perform a fixed set of suturing tasks in a laparoscopic pelvic-trainer. The laparoscopic needle drivers compared were (1) the Ethicon driver (E 705R), (2) Karl Storz (KS) pistol grip (26173 KC), (3) KS finger grip (26167 SK), and (4) KS palm grip (26173 ML). Times were recorded for each operator to grasp and position a needle for suturing in a particular angle, as well as to throw a horizontal and a vertical stitch and tie a single square knot using 2-0 Vicryl suture with a taper CT-1 needle. Subsequently, participants were asked to complete a subjective questionnaire rating the drivers. RESULTS: The average suturing time provided the most discriminatory power in comparing the needle drivers. For experienced operators, the KS pistol grip allowed faster suturing times than did the KS finger grip and the KS palm grip but not the Ethicon driver. For novice users, the Ethicon driver allowed faster suturing times than did the KS finger grip but not the KS pistol grip or the KS palm grip. In the subjective questionnaire, the KS pistol grip received the highest scores, and the KS finger grip received the lowest scores. CONCLUSION: Novice laparoscopists performed best with the KS pistol grip as well as the Ethicon laparoscopic needle drivers while experienced laparoscopists performed best with the pistol grip KS needle driver.     

Bariatric surgery improves cardiac function in morbidly obese patients with severe cardiomyopathy.

BACKGROUND: Longstanding morbid obesity can be associated with severe cardiomyopathy. However, the safety and efficacy of bariatric surgery in patients with severe cardiomyopathy has not been studied, and the effect of surgical weight loss on postoperative cardiac function is also unknown. In addition, morbidly obese patients have significantly increased mortality associated with cardiac transplantation, often precluding them from becoming recipients. METHODS: A retrospective study of patients with a left ventricular ejection fraction < or =35% who underwent bariatric surgery (1998-2005) was performed. Short-term morbidity/mortality, length of stay, excess weight loss, pre- and postoperative left ventricular ejection fraction, and New York Heart Association (NYHA) functional class were assessed. RESULTS: A total of 14 patients (10 men and 4 women) with a mean preoperative body mass index of 50.8 +/- 2.04 kg/m(2) underwent bariatric surgery (10 underwent laparoscopic Roux-en-Y gastric bypass, 1 open Roux-en-Y gastric bypass, 2 sleeve gastrectomy, and 1 laparoscopic gastric banding). The complications were pulmonary edema in 1, hypotension in 1, and transient renal insufficiency in 2. The median length of stay was 3.0 days (range 2-9). The mean excess weight loss at 6 months was 50.4%, with a decrease in the mean body mass index from 50.8 +/- 2.04 kg/m(2) to 36.8 +/- 1.72 kg/m(2). The mean left ventricular ejection fraction at 6 months had significantly improved from 23% +/- 2% to 32% +/- 4% (P = .04), correlating with improved functional capacity, as measured by the NYHA classification. Preoperatively, 2 patients (14%) had an NYHA classification of IV, 6 (43%) a classification of III, and 6 (43%) a classification of II. At 6 months postoperatively, no patient had an NYHA classification of IV, 2 (14%) had a classification of III, and 12 (86%) an NYHA classification of II. Two patients had undergone cardiac transplant evaluations preoperatively and underwent successful transplantation after weight loss. CONCLUSION: The results of our study have shown that bariatric surgery for patients with cardiomyopathy is feasible and effective. Surgically induced weight loss results in both subjective and objective improvement in cardiac function. In addition, surgical weight loss can provide a bridge to transplantation in patients who were prohibited secondary to their morbid obesity.