Immunologic heterogeneity of diffuse large cell lymphoma

The cellular lineage of 57 diffuse large-cell lymphomas (DLCLs) was determined using a panel of monoclonal antibodies directed against lineage-restricted and -associated T, B, and monocyte antigens. The majority (82%) were of B cell lineage as determined by the expression of sig and/or B1, with the remaining 16% being of T cell lineage and 2%, of monocyte-myeloid lineage. By the expression of other B cell- restricted and -associated antigens, two major and two minor subgroups could be identified. These subgroups expressed the following phenotypes: (1) B1+B4+sIG+B2- (51%); (2) B1+B4+sIg+B2+ (29%); (3) B1+B4+sIg-B2+ (10%); and (4) B1+B4-sIg+B2- (10)%. The morphology of transformed lymphocytes, the weak to absent expression of the early B cell antigens B2 and sIgD, and the absence of the late B cell differentiation antigens PCA-1 and PC-1 suggested that these tumors were the neoplastic counterparts of normal B cells at the mid-stages of differentiation. Further support for the notion that B-DLCLs correspond to transformed B lymphocytes was concluded from the observation that B cells could be identified in normal spleen that expressed the cell surface phenotype and morphological appearance of the majority of B- DLCLs.     

Abnormal clonogenic potential of T cells from multiple myeloma patients

Peripheral blood lymphocytes (PBLs) from multiple myeloma patients are defective in both proportion and absolute numbers of OKT4+ cells and have a normal proportion but reduced absolute number of OKT8+ cells. To assess the functional capabilities of the T cells in myeloma patients, we cloned the T cells in PBLs using limiting dilution conditions in which 100% of OKT4+ and OKT8+ T cells in normal PBLs are able to form a clone. In contrast, the OKT8+ cells from PBLs of five of seven multiple myeloma patients were severely compromised in their clonogenic potential; only 7% to 25% of OKT8+ T cells appeared to give rise to a clone. Clonogenic potential of the OKT4+ cells in patients was more nearly normal. Analysis of two multiple myeloma patients with abnormally low numbers of T cells in PBLs revealed the existence of abnormalities in the progenitors of T cell clones. In both patients, two to three times as many T cell clones were observed as would have been expected based on the number of PBLs cultured at limiting dilution, indicating that OKT4-8- cells in PBLs are capable of giving rise to OKT4+ and, at lower frequency, to OKT8+ clonal progeny in vitro. We conclude that purely quantitative assessment of T cell subsets should be interpreted with caution, since proportionately normal numbers of OKT8+ cells in patient PBLs are seriously compromised in their ability to give rise to clonal progeny in vitro, and since there appears to be a OKT4-8- population of T cells in PBLs that are committed to become OKT4+ or OKT8+ T cells, but are unable to do so in vivo.     

Predictive factors of excess body weight loss 1?year after laparoscopic bariatric surgery

Background

Bariatric surgery (BS) is widely accepted for the treatment of patients with morbid obesity (MO). We aimed to determine presurgical predictors of and surgical technique-related differences in excess weight loss (EWL) 1?year after BS.

Methods

This retrospective study included 407 subjects (F/M 3:1, median age?=?44?years) who underwent laparoscopic Roux-en-Y gastric bypass (RYGB, n?=?307) or sleeve gastrectomy (SG, n?=?100) at our University Hospital and were evaluated 1?year after surgery.

Results

Baseline median (min–max) body mass index (BMI) was 47?kg/m² (range?=?36–71). BMI was higher in the SG than in the RYGB group (53 vs. 46?kg/m², p?p?p?=?0.2), was lower in diabetic than in nondiabetic subjects (71?±?17% vs. 79?±?17%, p?p?p?=?0.4) after taking into account baseline BMI. Multiple regression and logistic analysis showed that younger individuals with lower BMI but higher WC, and lower HbA1c and TG, had higher EWL and a higher rate of successful (EWL?≥?60%) weight loss.

Conclusions

Our data indicate that some of the characteristics that would have subjects referred early for BS were associated with higher weight loss. Therefore, the timing of laparoscopic BS might be an important factor for MO individuals in which medical weight loss intervention has failed.     

Evidence That Hyperglycemia After Recovery From Hypoglycemia Worsens Endothelial Function and Increases Oxidative Stress and Inflammation in Healthy Control Subjects and Subjects With Type 1 Diabetes

Currently there is debate on whether hypoglycemia is an independent risk factor for atherosclerosis, but little attention has been paid to the effects of recovery from hypoglycemia. In normal control individuals and in people with type 1 diabetes, recovery from a 2-h induced hypoglycemia was obtained by reaching normoglycemia or hyperglycemia for another 2 h and then maintaining normal glycemia for the following 6 h. Hyperglycemia after hypoglycemia was also repeated with the concomitant infusion of vitamin C. Recovery with normoglycemia is accompanied by a significant improvement in endothelial dysfunction, oxidative stress, and inflammation, which are affected by hypoglycemia; however, a period of hyperglycemia after hypoglycemia worsens all of these parameters, an effect that persists even after the additional 6 h of normoglycemia. This effect is partially counterbalanced when hyperglycemia after hypoglycemia is accompanied by the simultaneous infusion of vitamin C, suggesting that when hyperglycemia follows hypoglycemia, an ischemia–reperfusion-like effect is produced. This study shows that the way in which recovery from hypoglycemia takes place in people with type 1 diabetes could play an important role in favoring the appearance of endothelial dysfunction, oxidative stress, and inflammation, widely recognized cardiovascular risk factors.Recent evidence suggests that hypoglycemia may play an important role in the vascular complications of diabetes (1). Hypoglycemia causes oxidative stress (2), inflammation (3), and endothelial dysfunction (4). Oxidative stress is considered the key player in the pathogenesis of diabetes complications (5). During hyperglycemia, oxidative stress is produced at the mitochondrial level (5), similarly as in hypoglycemia (2). Therefore, oxidative stress might be considered the common factor linking hyperglycemia, hypoglycemia, and the vascular complications of diabetes. Consistent with this hypothesis is the evidence that hyperglycemia (6) and hypoglycemia both produce endothelial dysfunction and inflammation through the generation of oxidative stress (4,7). Endothelial dysfunction and inflammation are well-recognized pathogenic factors for vascular disease, particularly in diabetes (8).There is, however, evidence that free radical production rises, not only during hypoglycemia but particularly during glucose reperfusion after hypoglycemia (9). In both mice and cultured neurons, hypoglycemia, followed by different concentrations of glucose reperfusion, has been linked to a degree of superoxide production and neuronal death that increased proportionally with glucose concentrations during the reperfusion period (9).Until now, little attention has been given to studying the effects of recovery from hypoglycemia. The aim of this study was to evaluate these effects and, in particular, to determine if the level of glycemia reached during recovery could have a different impact, in vivo, on oxidative stress generation, inflammation, and endothelial function.     

Dual-setting calcium phosphate cement modified with ammonium polyacrylate

alpha-Tricalcium phosphate bone cement, as formerly designed and developed by Driessens et al., consists of a powder composed by alpha-tricalcium phosphate (alpha-TCP) and hydroxyapatite (HA) seeds, and an aqueous solution of Na2HPO4 as mixing liquid. After mixing powder and liquid, alpha-TCP dissolves into the liquid and calcium deficient hydroxyapatite (CDHA), more insoluble than the former, precipitates as an entanglement of crystals, which causes the setting and hardening of the cement. alpha-TCP bone cement offers several advantages in comparison to calcium phosphate bioceramics and acrylic bone cements as bone graft and repairing material, like perfect adaptability to the defect size and shape, osteotransductibility, and absence of thermal effect during setting. The main handicap is its low mechanical strength. Therefore, approaching its mechanical strength to that of human bone could considerably extend its applications. In the present work, an in situ polymerization system based on acrylamide (AA) and ammonium polyacrylate (PA) as liquid reducer was added to alpha-TCP cement to increase its mechanical strength. The results showed that the addition of 20 wt% of acrylamide and 1 wt% AP to the liquid increased the compressive and tensile strength of alpha-TCP bone cement by 149 and 69% (55 and 21 MPa), respectively. The improvement in mechanical strength seems to be caused by a decrease of porosity and the reinforcing effect of a polyacrylamide network coexisting with the entanglement of CDHA crystals. The studied additives do not affect the nature of the final product of the setting reaction, CDHA, but promote the reduction of its crystal size.     

Outcome of 28 split liver grafts

Our aim is to present our experience with split liver transplantation. From 1992-2002, 14 livers were split to obtain 28 grafts that were transplanted to 12 adults and 16 children. Ex situ splitting was performed in all cases. The left graft consisted of the left lateral segment (segments II-III) in 11 cases and the left lobe in three, depending on the size of the pediatric recipient. Pediatric recipients were of mean age 3, 4 years; mean weight 13 kg; six emergency cases for fulminant hepatic failure or urgent retransplantation and seven of 10 elective cases for biliary atresia. Postoperative mortality rate was 31% (five cases), including four of six emergency cases and one elective case (10%). The main cause was multiorgan failure. Technical complications were: one arterial thrombosis, one portal vein thrombosis, and four biliary complications. Eleven patients are alive and well. Adult recipients were of mean age 53 years. The indications were hepatocellular carcinoma in six cases, liver cirrhosis of various etiologies in five, and one recurrence of hepatitis C in a graft. Two patients died during the postoperative period from sepsis after retransplantation for primary nonfunction of the split graft and multiorgan failure with sepsis. One-year actuarial survival was 84%. CONCLUSIONS: The results of split liver transplantation in elective cases are similar to whole liver transplantation, whereas patient survival among emergency cases is low due to the critical condition of the patients.     

Sequential compression devices as prophylaxis for venous thromboembolism in high-risk colorectal surgery patients: reconsidering American Society of Colorectal Surgeons parameters

The American Society of Colorectal Surgeons (ASCRS) recently endorsed low-molecular-weight heparin and low-dose heparin as primary prophylaxis for venous thromboembolism (VTE) in highest-risk patients. Our study evaluates the feasibility of sequential compression device (SCD) use for VTE prophylaxis in these patients. Computerized databases of discharge diagnoses from three hospitals were reviewed. All patients with colorectal cancer or inflammatory bowel disease during a 7-year period were identified. Those who underwent major abdominal surgery and received VTE prophylaxis exclusively with SCDs were selected for the study. Patients diagnosed with postoperative VTE were identified through review of the three databases and of patient records for 90 days after surgery. One thousand two hundred eighty-one patients classified as highest-risk under the published ASCRS parameters underwent major abdominal surgery and received SCDs perioperatively. The incidence of clinically detectable postoperative VTE was 0.78 per cent. There were trends toward lower incidence among patients with malignancy (0.53%) compared with inflammatory bowel disease (1.48%, P = 0.09), and those with abdominal compared to pelvic procedures (0.62% vs. 1.04%, P = 0.41). Prophylaxis for perioperative VTE solely with SCD is a viable option for patients classified as highest-risk under ASCRS parameters.     

First orthotopic liver transplantation in patient with biliary atresia and situs inversus in spain

Biliary atresia is the most common indication for liver transplantation in the pediatric age group. The Kasai portoenterostomy has become established as the primary treatment for biliary atresia. If portoenterostomy fails, death before 2 years of age is likely without liver transplantation. The most common multiple malformation syndrome associated with biliary atresia is polysplenia syndrome, which forms a constellation of defects of body symmetry, splenic development and vascular anomalies, including situs inversus, polysplenia and others. The situs inversus was formerly considered an absolute contraindication for liver transplantation. Recently however, several case reports have been published suggesting that neither situs inversus nor this particular subset of vascular abnormalities should be considered contraindications to liver transplantation. We present one case of liver transplantation performed in patient with biliary atresia, situs inversus and polysplenia. This is the first report described in Spain for a liver transplant in a child with biliary atresia plus situs inversus.     

Preoperative hemoglobin as the only predictive factor of transfusional needs in knee arthroplasty

OBJECTIVE: To study transfusion requirements in total knee anthroplasty (TKA) in order to estimate needs and consider possible ways to improve principled management. PATIENTS AND METHODS: Retrospective study of all TKAs performed over a period of 3 months in 2000. We analyzed age, medication, hypertension, participation in a predeposit autologous blood program (PABP), drainage bleeding, transfusion requirements and hemoglobin (Hb) levels. RESULTS: One hundred ten TKAs were performed. Ten were excluded from analysis (2 TKA reviews, 5 patients with coronary artery disease and 3 with chronic bronchial diseases). We reserved a mean 2.46 +/- 0.5 units of packed red cells (range 2-3), and 30% of the patients were transfused with a mean 0.62 +/- 0.99 units (range 0-4). In 15 cases (50%), transfusions were not clearly indicated or were related only to the surgical procedure. All 5 PABP patients were transfused, but not with homologous blood, even through 4 had Hb levels over 9 g/dL. Only Hb level was an independent risk factor for transfusion. Transfusions were given to 80% of patients with Hb levels under 12 g/dL, to 18.8% of those with hemoglobin levels over 14 g/dL, and to 35.7% of those with Hb levels between 12 g/dL and 14 g/dL. CONCLUSIONS: Preoperative Hb level was the single predictor of transfusion in our series of patients. In some cases the transfusion trigger was too liberal. Alternatives to homologous transfusion were hardly used, with PABP applied in only 5% of the cases. These findings encourage us to continue trying to improve the PABP program and transfusion criteria, to introduce alternatives and to improve baseline Hb levels.     

Potential Role of NKG2D and Its Ligands in Organ Transplantation: New Target for Immunointervention

NKG2D is one of the best characterized activating receptors on Natural Killer (NK) and CD8+ T cells. This receptor recognizes several different ligands (MICA/MICB and ULBPs) induced by cellular stress and infection. In addition to the role described in cancer surveillance, recent data highlight the importance of NKG2D and its ligands in organ transplantation. Allografts show evidence of MICA and MICB expression in both acute and chronic rejection. The presence of anti-MICA antibodies has been correlated with incidence of graft rejection. Furthermore, NKG2D-ligand engagement activates NK cells, which provides T-cell costimulation, and enhances antigen specific CTL-mediated cytotoxicity. Activated NK cells may function as a bridge between innate and adaptive immunity associated with transplantation. Activated NK cells in response to IL-15 can also trigger organ rejection through NKG2D and affect the maturation of both donor and recipient antigen presenting cells (APCs) and ultimately the T-cell allogeneic response. Regulatory T cells, which modulate T-cell responses in organ transplantation and infections, were reduced in numbers by NK cells exposed to intracellular pathogens, possibly via interaction with one NK2GD receptor. Blockage of NKG2D-NKG2D-L interactions provides a novel pathway for development of inhibitors. These studies have important clinical and therapeutic implications in solid organ transplantation.