IgG subclass serum levels in systemic lupus erythematosus patients

IgG subclass levels of sera from 105 patients with systemic lupus erythematosus (SLE) were determined by immunonephelometric assay. Patients were divided into two groups according to clinical activity of the disease: active disease and remission. Forty-five normal controls were also measured. We found a significant increase of IgG1 (p = 0.000), IgG2 (p = 0.000), and IgG3 (p = 0.000) in SLE sera, while IgG4 (p = 0.494) values did not differ significantly from those of controls. When patients were divided according to clinical activity, decrease of IgG3 concentration was observed in the patients in remission. In contrast, the concentrations of IgG1, IgG2, and IgG4 subclass were similar between the two groups (p > 0.05). Our data suggest that differential increase of IgG subclasses during the course of SLE may be of relevance to the pathogenesis of the disease.     

The significance of platelet activation in rheumatoid arthritis

We evaluated the significance of platelet activation in patients with rheumatoid arthritis (RA). The expression of CD62P and CD63 by platelets was determined using flow cytometry in 18 active RA patients, 10 remission RA and 15 normal controls. Meanwhile, the erythrocyte sedimentation rate (ESR) and C-reactive protein was also determined in all groups. The expression of CD62P in active RA patients (11.88 ± 2.47%) was significantly higher than that in remission RA group (2.85 ± 1.60%; P < 0.01) and control group (2.78 ± 1.04%; P < 0.01). The expression of CD63 in active RA patients (9.90 ± 3.02%) was significantly higher than that in remission RA group (4.11 ± 2.00%; P < 0.01) and control group (4.13 ± 1.85%; P < 0.01). The level of CRP (54.33 ± 23.35 mg/l) and ESR (86.06 ± 33.67 mm/h) in active RA patients was higher than that in remission RA group (2.55 ± 1.01 mg/l, 14.70 ± 4.57 mm/h; P < 0.01 for both) and normal control group (3.21 ± 2.18 mg/l, 12.25 ± 5.05 mm/h; P < 0.01 for both). There was a positive correlation between CD62P and ESR (r = 0.5224, P < 0.01) and also a positive correlation between CD62P and CRP (r = 0.7048, P < 0.01) as well as between CD63 and ESR (r = 0.4476, P < 0.05) but no correlation between CD63 and CRP. Platelet activation may be a sign of RA exacerbation.     

Correlation of telomerase activity to apoptosis and survival in adult acute lymphoblastic leukemia: an Egyptian single-center study

Telomerase is activated in most tumors, but suppressed in normal human somatic cells. Current evidence indicates that telomerase reactivation is a critical step in carcinogenesis, with a close relationship to apoptosis. The goal of this study was to investigate the levels and relationship of telomerase activity to apoptosis and its impact on the survival of Egyptian adult acute lymphoblastic leukemia patients. Telomerase activity was quantified by polymerase chain reaction (PCR) and detected by enzyme-linked immunosorbent assay (ELISA), while apoptosis was measured at the single-cell level by fluorescence in situ detection using flow cytometry in 15 control subjects and 40 acute lymphoblastic leukemia (ALL) patients at presentation. Telomerase activity in ALL patients was negatively correlated to apoptosis [percent and mean fluorescence intensity (MFI)] (p < 0.001 for percent and p < 0.001 for MFI) and to the 4-year survival rate (p < 0.05), to which apoptosis (percent and MFI) was consequently positively correlated (p < 0.001 for percent and p < 0.05 for MFI). For telomerase, the highest positive predictive value (PPV) for mortality (93.3%) was at a cut-off value of 13 amol/ml, while those for apoptosis (85% for percent of apoptotic cells and 90.9% for MFI) were at a cut-off of 8% and 0.19 MFI. This makes the measurement of telomerase activity in ALL patients a potential tool to predict disease with unfavorable outcome and a candidate tumor marker.     

Association of tri-nucleotide (CAG and GGC) repeat polymorphism of androgen receptor gene in Taiwanese women with refractory or remission rheumatoid arthritis

We investigated the relationship between CAG and GGC repeat polymorphism of the androgen receptor (AR) gene and rheumatoid arthritis (RA) in female patients with different disease subtypes. This case-control study enrolled 215 women in three groups: RA patients refractory to standardized therapy (n = 51); RA patients at complete remission phase (n = 60); and healthy controls (n = 104). CAG and GGC repeat lengths were determined by automated fluorescence-based DNA fragment-sizing method. Demographic data, allele lengths, allele distribution, and zygosity status of CAG/GGC repeats were assessed for the three groups. Refractory RA patients tend to have a significantly younger onset age of RA and more elevated erythrocyte sedimentation rates than do remission RA patients. Mean and median values of CAG and GGC repeat lengths are similar in both RA and control patients. However, RA patients harboring any long CAG alleles with more than 23 repeats had an increased risk of a refractory course, whereas differences in risk were not observed between these patients and RA subtypes harboring any long GGC alleles with more than 16 repeats. In addition, the homozygous frequency of CAG but not GGC alleles was lower in refractory RA than in remission RA patients or in controls (p = 0.042). Neither CAG nor GGC repeat lengths had a significant relationship with rheumatoid factor reactivity. Our observations indicate that short CAG repeats of the AR gene with higher transactivation activity may have protective effects against refractory course of RA development and that homozygous frequency of CAG alleles may be involved in the disease remission subtype. In contrast, lack of association of GGC polymorphism and RA was also observed. Together, these data imply that CAG but not GGC alleles in the AR polymorphism may play an important role in modulating the disease pattern of RA among Taiwanese women.     

Race/Ethnicity and Risk of AIDS and Death Among HIV-infected Patients with Access to Care

BACKGROUND  Prior studies evaluating racial/ethnic differences in responses to antiretroviral therapy (ART) among HIV-infected patients have not adequately accounted for many potential confounders, and few have included Hispanic patients. OBJECTIVE  To identify racial/ethnic differences in ART adherence, and risk of AIDS and death after ART initiation for HIV patients with similar access to care. DESIGN  Retrospective cohort study. PARTICIPANTS  4,686 HIV-infected patients (66% White, 20% Black, and 14% Hispanic) initiating ART and who were enrolled in an integrated healthcare system. MEASUREMENTS  Main outcomes evaluated were ART adherence, new AIDS clinical events, and all-cause mortality. The potential confounding effects of demographics, socioeconomic status, ART parameters, HIV disease stage, and other clinical parameters were considered in multivariable models. RESULTS  Adjusted mean adherence levels were higher among White (70.1%; ref) compared with Black (64.2%; P < 0.001) and Hispanic patients (65.2%; P < 0.001). Adjusted hazard ratios (HR) for the risk of new AIDS events (White patients as reference) were 1.3 (P = 0.09) for Black and 0.9 (P = 0.64) for Hispanic patients. The adjusted HR for AIDS comparing Hispanic to Black patients was 0.7 (P = 0.11). Hispanic patients had fewer deaths compared with other racial/ethnic groups, particularly cancer and cardiovascular-related. However, adjusted HRs for death were 1.2 (P = 0.37) and 0.9 (P = 0.62) for Black and Hispanic patients, respectively, compared with White patients and 0.9 (P = 0.63) for Hispanic compared with Black patients. Adjustment for adherence did not change inferences for AIDS or death. CONCLUSIONS  In the setting of similar access to care, we did not observe a disparity for the risk of clinical events for racial/ethnic minorities, despite lower ART adherence. This material was presented at the 4th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention, Sydney, Australia, July 22–25, 2007 (#WEPEB107). This research was supported by a Community Benefit grant from Kaiser Permanente Northern California and grant number K01AI071725 from the NIAID.     

The significance of platelet activation in ankylosing spondylitis

The objective of this study was to explore the significance of platelet activation in patients with ankylosing spondylitis (AS). Thirty-five AS patients and 15 normal controls were selected from November 2005 to October 2006. The number of CD62P- and CD63-positive cells were detected by flow cytometry. At the same time, the erythrocyte sedimentation rate (ESR), platelet count (PLT) and C-reactive protein (CRP) were determined in both groups. The percentage of CD62P-positive cell in AS patients (13.60 ± 7.64%) was significantly higher than that in control group (2.78 ± 1.04%; P < 0.01). The percentage of CD63-positive cell in AS patients (6.92 ± 4.16%) was significantly higher than that in control group (4.13 ± 1.85%; P < 0.05). The levels of CRP (20.18 ± 23.17 mg/l), PLT (259.54 ± 102.59 × 10⁹/l) and ESR (36.86 ± 31.23 mm/h) in AS patients were higher than those in normal controls, respectively (3.21 ± 2.18 mg/l, P < 0.01; 197.00 ± 55.70 × 10⁹/l, P < 0.01; 12.25 ± 5.05 mm/h, P < 0.05). Platelet activation may be a sign of AS exacerbation.     

Low cortisol levels in active juvenile idiopathic arthritis

The aim of our study was to evaluate the neuroendocrine system in patients with juvenile idiopathic arthritis (JIA) regarding the activity of disease. Twenty-one JIA patients (mean age ± standard deviation 10.5 ± 4.1 years) were included. None of the patients was taking steroids or antitumor necrosis factor-α therapy during this study. Ten healthy volunteers and ten volunteers with upper respiratory tract infection composed the control groups. Furthermore, ten of the 21 JIA patients were also evaluated during the remission period. Erythrocyte sedimentation rate, C-reactive protein, adrenocorticotropic hormone (ACTH), cortisol, prolactin, insulin-like growth factor-1 (IGF-1), insulin-like growth factor-binding protein 3, free T3, free T4, thyroid-stimulating hormone, interleukin-6 (IL-6) levels, and 24-h urinary cortisol were evaluated both during the active period and remission. The median levels of ACTH and cortisol at 08:00 a.m. were significantly lower in patients with active JIA than patients in remission period and the control groups (p < 0.05). Furthermore, the median level of urine cortisol in active JIA patients was significantly lower than remission period and control groups (p < 0.05). The median level of IGF-1 was significantly lower in active patients than that of remission (p < 0.05). The median level of IL-6 in active JIA patients was significantly higher than those in remission and control groups (p < 0.05). Our preliminary study suggested that impaired secretion of adenohypophyseal hormones and distorted bilateral interactions between the immune and endocrine systems in JIA. Further studies are needed to clarify the consequences of the impaired hormone secretion in JIA.     

<Emphasis Type="Italic">Lens culinaris</Emphasis> agglutinin-reactive α-fetoprotein and protein induced by vitamin K absence II are potential indicators of a poor prognosis: a histopathological study of surgically resected hepatocellular carcinoma

Background We histopathologically examined Lens culinaris agglutinin-reactive α-fetoprotein (AFP-L3)-positive hepatocellular carcinoma (HCC) and protein induced by vitamin K absence (PIVKA) II-positive HCC to clarify the efficacy of these markers for predicting a poor prognosis. Methods Serum AFP-L3 and PIVKA II was measured in 110 HCC patients. AFP-L3 was measured by lectin-affinity electrophoresis coupled with antibody-affinity blotting, and PIVKA II by using a high-sensitivity kit. The growth type, capsule formation, capsule infiltration, portal vein invasion, intrahepatic metastasis and histological tumor grade were evaluated pathologically. Results Thirty-eight (35%) HCC patients were AFP-L3-positive, and 63 (57%) were PIVKA II-positive. In AFP-L3-positive HCC, the frequencies of an infiltrative growth type (positive : negative = 66% : 42%, P = 0.027) and a poorly differentiated type (positive : negative = 32% : 6%, P < 0.001) were significantly higher than in AFP-L3-negative HCC. In PIVKA II-positive HCC, the frequencies of an infiltrative growth type (positive : negative = 62% : 28%, P < 0.001), vascular invasion (positive : negative = 63% : 26%, P < 0.001), and intrahepatic metastasis (positive : negative = 38% : 4%, P < 0.001) were significantly higher than in PIVKA II-negative HCC. In both AFP-L3- and PIVKA II-positive HCC, the frequency of a poorly differentiated growth type was significantly higher than in HCC positive for either AFP-L3 or PIVKA II or HCC negative for both AFP-L3 and PIVKA II (both positive : either positive : both negative = 37% : 12% : 0%; P = 0.014, P < 0.001, respectively). Conclusions AFP-L3 was related to progression from moderately differentiated to poorly differentiated HCC, whereas PIVKA II was more specific to vascular invasion. PIVKA II is therefore likely to be a useful indicator of vascular invasion.     

The relation of serum vascular endothelial growth factor level with disease duration and activity in patients with rheumatoid arthritis

Vascular endothelial growth factor (VEGF) is known to be involved in the pathogenesis of rheumatoid arthritis (RA). In order to elucidate the association between VEGF levels and RA disease activity, VEGF concentrations were measured in RA patients at different phases and severity levels. Thirty-eight healthy subjects and 40 patients with RA were prospectively included in the study. Subjects were further categorized into four subgroups (high, moderate, low, or remission) using the disease activity score-28 (DAS28) scoring system. VEGF levels were significantly higher in patients than controls (p < 0.001). VEGF levels differed significantly in controls, early and late-phase RA patients (p = 0.002). A significant difference was found between controls and patients with high RA disease activity scores (p < 0.0001). VEGF levels were not correlated with age (r = −0.016; p = 0.921) or sex (r = 0.209; p = 0.921). VEGF values were correlated with erythrocyte sedimentation rate (r = 0.445; p = 0.004), but was not correlated with serum rheumatoid factor levels (r = −0.130; p = 0.424) in the patient group. In conclusion, higher VEGF levels are associated with late phase and high disease activity in RA, independent of age and sex.     

Late spontaneous remissions in severe adult autoimmune thrombocytopenia

We report on four cases (three women, one man, age at diagnosis 26–61 years) with severe autoimmune thrombocytopenia (AITP) who were refractory to initial steroid therapy (n = 4), to subsequent splenectomy (n = 2), azathioprine (n = 1), and cyclosporine (n = 1). Over years they received low-dose continuous or intermittent steroid therapy. After 6 to 31 years these patients achieved a “spontaneous” complete remission (CR) (n = 3) or partial remission (PR) (n = 1) unrelated to any specific second or third line treatment; CR/PR are sustained for 0.5+ to 9+ years. These data indicate that spontaneous remissions may occur in AITP even after a long duration of the disease.     

Fecal Lactoferrin and Calprotectin After Ileocolonic Resection for Crohn’s Disease

Purpose This study was designed to assess the role of fecal lactoferrin and calprotectin as markers of intestinal inflammation in patients with Crohn’s disease who have undergone ileocolonic resection. Methods Sixty-three patients who had undergone ileocolonic resection for Crohn’s disease with a median follow-up of 40.5 (range, 5–102) months were enrolled. Clinical examination and blood test were performed, and fecal lactoferrin and calprotectin levels were dosed. The predictors for fecal lactoferrin and calprotectin levels that resulted to be significant at the univariate analyses were included in two multiple regression analysis models. Results The mean lactoferrin level was 21 ± 3.9 μg/g and the mean calprotectin fecal level was 247 ± 22.7 ng/ml. C-reactive protein levels (P < 0.01), calprotectin levels (P < 0.01), and the presence of clinical recurrence (P = 0.04) resulted to be independent predictors of lactoferrin levels. Only lactoferrin levels resulted to be an independent predictor for calprotectin fecal levels (P < 0.01). Conclusions Crohn’s disease patients maintain high fecal levels of lactoferrin and calprotectin at long-term follow-up after resection of the diseased bowel even in case of clinical remission. The significant correlation between the two fecal markers may be the expression of the ongoing intestinal inflammation. Only lactoferrin significantly correlated with C-reactive protein and showed a reliable threshold value for systemic inflammation. Lactoferrin fecal levels may be a reliable indicator for intestinal inflammation influencing the systemic inflammatory status. The third predictor of lactoferrin fecal level was the presence of episodes of clinical recurrence during the postoperative follow-up. Supported in part by the MIUR grant ex 60%.     

Boswellia serrata extract for the treatment of collagenous colitis. A double-blind, randomized, placebo-controlled, multicenter trial

Background and aims The objective of this study was to investigate the effect of Boswellia serrata extract (BSE) on symptoms, quality of life, and histology in patients with collagenous colitis. Materials and methods Patients with chronic diarrhea and histologically proven collagenous colitis were randomized to receive either oral BSE 400 mg three times daily for 6 weeks or placebo. Complete colonoscopy and histology were performed before and after treatment. Clinical symptoms and quality of life were assessed by standardized questionnaires and SF-36. The primary endpoint was the percentage of patients with clinical remission after 6 weeks (stool frequency ≤3 soft /solid stools per day on average during the last week). Patients of the placebo group with persistent diarrhea received open-label BSE therapy for a further 6 weeks. Results Thirty-one patients were randomized; 26 patients were available for per-protocol-analysis. After 6 weeks, the proportion of patients in clinical remission was higher in the BSE group than in the placebo group (per protocol 63.6%; 95%CI, 30.8–89.1 vs 26.7%, 95%CI, 7.7–55.1; p = 0.04; intention-to-treat 43.8% vs 26.7%, p = 0.25). Compared to placebo, BSE treatment had no effect on histology and quality of life. Five patients discontinued BSE treatment prematurely. Discontinuation was due to adverse events (n = 1), unwillingness to continue (n = 3), or loss to follow-up for unknown reasons (n = 1). Seven patients received open-label BSE therapy, five of whom achieved complete remission. Conclusions Our study suggests that BSE might be clinically effective in patients with collagenous colitis. Larger trials are clearly necessary to establish the clinical efficacy of BSE.     

Clofarabine and high-dose cytosine arabinoside in the treatment of refractory or relapsed acute myeloid leukaemia

Clofarabine (40 mg/m²/day × 5) and high-dose cytosine arabinoside (Ara-C, 1–2 g/m²/day × 5) were used in 10 men and 11 women, at a median age of 45 (22–62) years, with refractory (N = 4) and relapsed (N = 17) acute myeloid leukaemia, after a median of 3 (2–5) prior regimens. Grade 4 myelosuppression was observed in all cases, with two patients dying of bacterial sepsis. Nine patients achieved a complete remission. Disease status, number of prior therapies, and cytogenetic aberrations were not associated with the outcome. However, remission was only achieved with Ara-C at 2 g/m²/day and not 1 g/m²/day (9/15 versus 0/4, P = 0.03).     

Multiple myeloma-associated amyloidosis is an independent high-risk prognostic factor

Several prognostic factors have been recognized in patients with multiple myeloma (MM). Among the most important are: the serum levels of β2-microglobulin, albumin, and LDH; the labeling index; and an abnormal karyotype. Patients with amyloidosis (AL) have poor prognosis; however, little is known concerning the prognostic significance of AL associated to MM. In 201 consecutive patients with de novo MM, we performed a fat-pad biopsy needle aspiration (FPBNA) that was stained with Congo red. Sixty eight (34%) patients had AL and a poorer prognosis disease: lower performance status, presence of B symptoms, higher LDH and calcium values, and worse response to chemotherapy. Cox regression model for overall survival detected three variables having independent prognostic significance: the presence of AL (RR = 3.4, P < 0.004), serum albumin levels <3.5 g/dl (RR 3.2, p < 0.005), and patients not achieving complete remission or very good partial remission (RR 2.9, p < 0.02). In 28% of patients with de novo MM, FPBNA was useful to detect incidental amyloidosis. During follow-up, 69% of these patients had symptoms of AL. Excluding 16 patients with obvious symptoms of AL at diagnosis, overall survival was worse in patients who developed later symptoms of AL. MM-associated AL represents a poorer prognosis disease even in the absence of symptoms at diagnosis, and this specific association may be considered as an independent high-risk prognostic factor. The routine study of periumbilical fat-pad tissue should be mandatory in all patients with MM.     

Results of a randomized double-blind placebo-controlled trial evaluating sequential high-dose cytosine arabinoside/mitoxantrone chemotherapy with or without granulocyte/macrophage-colony-stimulating factor in high-risk myelodysplastic syndromes

A prospective, randomized, double-blind placebo-controlled trial was designed to evaluate the impact of granulocyte/macrophage-colony-stimulating factor (GM-CSF) on the efficacy of sequential high-dose cytosine arabinoside/mitoxantrone chemotherapy (S-HAM) in adult patients with high-risk myelodysplastic syndromes (MDS). GM-CSF or placebo was given subcutaneously once daily at a dose of 250 μg/m², starting 48 h prior to chemotherapy, and continued until neutrophil recovery. Owing to high toxicity and slow patient recruitement the study was closed and unblinded after 31 patients had been enrolled; 15 were randomized to receive placebo and 16 to receive GM-CSF. A total of 29 patients were evaluable for response; their median age was 57 years. Ten patients achieved a complete remission (34.5%), 9 patients had persistent MDS (31%), 10 patients died within 6 weeks after the onset of treatment (early death) (34.5%). The median remission duration was 190 days (range: 2.5–45 months). Among the 29 evaluable patients no significant differences could be found between the two study arms regarding complete remission rate [GM-CSF: 31% (5/16) versus placebo: 38% (5/13) P = 0.45], rate of persistent MDS [GM-CSF: 25% (4/16) versus 38% (5/13) P = 0.35), early death rate [44% (7/16) versus 23% (3/13) P = 0.22] and remission duration (GM-CSF: 87 days versus placebo 221 days). Duration of granulocytopenia (median: 33 days with GM-CSF) versus 35 days with placebo) and frequency of infectious episodes were not significantly influenced by GM-CSF. The small number of patients finally analyzed means that no definite conclusions about the effect of GM-CSF can be reached. Received: 3 June 1998 / Accepted: 5 January 1999     

Adacolumn Selective Leukocyte Adsorption Apheresis in Patients with Active Ulcerative Colitis: Clinical Efficacy,Effects on Plasma IL-8, and Expression of Toll-like Receptor 2 on Granulocytes

Adacolumn selective granulocyte and monocyte apheresis (GMA) depletes activated leukocytes in patients with ulcerative colitis (UC). However, this per se cannot fully explain the efficacy of GMA. We have investigated the effects of GMA on the expression of toll-like receptors (TLRs) and plasma interleukin-8 (IL-8). Twenty-two patients with clinical activity index (CAI) of 5–17, 15 with total colitis and 7 with left-sided colitis, were included. Each patient could receive up to 10 GMA sessions, at 1 or 2 sessions per week. GMA was added to the patients’ ongoing medication following a relapse or worsening UC, but no additional medication was given. Further, at entry and pre-GMA, blood samples were taken for full blood cell count, expression of TLRs on leukocytes, and plasma IL-8. Seventy-five percent of patients achieved remission after the 10th session (CAI, ≤4; P < 0.005) and there was a marked fall in C-reactive protein (P < 0.01), plasma IL-8 (P < 0.001), and granulocytes (P < 0.05) but an increase in lymphocytes (P < 0.05). The expression of TLR2 on granulocytes was down-modulated (P < 0.05) together with suppression of inflammatory cytokines produced by peripheral blood leukocytes. In conclusion, GMA appears to be an effective adjunct therapy to induce remission in the majority of patients, who are then spared from excess drug therapy. The procedure is associated with sustained immunomodulation. Control studies should strengthen these findings.     

Prognostic significance of CD95, P53, and BCL2 expression in extranodal non-Hodgkin’s lymphoma

Apoptosis-related proteins play an important role in lymphoma cell death during chemotherapy. In our study, we investigated the prognostic significance of CD95, BCL2, and P53 expression in extranodal non-Hodgkin’s lymphoma (NHL). We examined 71 patients with extranodal NHL [45 diffuse large B-cell lymphomas (DLBCLs) and 26 mucosa-associated lymphoid tissue lymphomas (MALTLs)], 35 male and 36 female, with a median age of 65.8 years. The most common site of origin was the stomach (N = 31). Paraffin-embedded specimens were analyzed immunohistochemically for CD95, BCL2, and P53 expression. Multivariate analysis revealed that in DLBCLs, positive CD95 and negative BCL2 expression were independent prognostic factors for overall survival. We reached the same conclusion for MALTLs, with positive CD95 and negative P53 expression. In DLBCLs, the 5-year overall survival rate was 71.5% for the CD95-positive cases and 35% for the CD95-negative cases (p = 0.004) and the 5-year overall survival was significantly better in BCL2-negative cases (70.8%) when compared to BCL2-positive cases (37%; p = 0.009). In MALTLs, the 5-year overall survival rate for the CD95-positive and CD95-negative groups was 89.5% and 42.9%, respectively (p = 0.004) and the 5-year overall survival rate was 50% for the P53-positive cases and 88.9% for the P53-negative cases (p = 0.016). In conclusion, positive CD95 expression proved to be a good prognostic factor of overall survival in both extranodal DLBCLs and MALTLs. In contrast, positive expression of BCL2 and P53 was found to be unfavorably associated with survival in extranodal DLBCLs and MALTLs, respectively.     

Impact of Tumor Location on Nodal Evaluation for Colon Cancer

Purpose Adequate lymph node evaluation is important to stage colon cancers and make adjuvant treatment decisions. Studies have demonstrated improved survival when ≥ 12 nodes are examined. Our objective was to assess differences in the adequacy of nodal evaluation for right vs. left colon cancers. Methods From the National Cancer Data Base (1998–2004), 142,009 N0M0 colon cancer patients were identified. Logistic regression was used to evaluate the number of nodes examined for right vs. left colectomies. Multivariable modeling was used to determine the impact of examining ≥ 12 nodes on survival. Results Of 142,009 patients, 79,444 (56 percent) had right colectomies, and 62,565 (44 percent) patients had left colectomies. More nodes were examined during right colectomies than left (median 12 vs. 8, P < 0.0001). When adjusted for patient, tumor, and hospital factors, patients undergoing left colectomy were less likely to have ≥ 12 nodes identified (P < 0.0001). Patients were more likely to have ≥ 12 nodes identified for right and left colon cancers at high-volume hospitals. Survival was better with examination of ≥ 12 nodes for right and left colon cancers (P < 0.0001). Conclusions Evaluating ≥ 12 nodes for right and left colon cancers is a feasible, clinically relevant, and modifiable factor that will likely improve patient outcomes. Presented in part at the meeting of The American Society of Colon and Rectal Surgeons, St. Louis, Missouri, June 2 to 7, 2007. Supported by a grant from the National Cancer Institute. Dr. Bilimoria is supported by the American College of Surgeons, Clinical Scholars in Residence program, and a research grant from the Department of Surgery, Feinberg School of Medicine, Northwestern University.     

Adhesion molecules in chronic ulcerative colitis

Background and aims The adhesion molecule expression in colonic mucosa is pivotal for transition from quiescent to active stage of ulcerative colitis (UC). The aim of the present study is to reveal the adhesion molecule profile of colonic mucosa in the active stage of UC and in remission. Materials and methods Biopsy specimens obtained from 14 patients with UC (seven with active disease and seven with UC in remission) and from seven controls were used. Immunohistochemistry was performed with antibodies against ICAM-1, VCAM-1, E-selectin, LFA-1, Mac-1, and VLA-4. Results In controls, slight ICAM-1 positivity was observed on thety endothelium of blood vessels of the mucosal and submucosal layer and only single ICAM-1-, Mac-1-, and LFA-1-positive cells were found. In all patients with UC, the endothelium of venules in the edematous mucosal and submucosal layers was ICAM-1-, VCAM-1-, and E-selectin-positive. Numerous ICAM-1- and LFA-1-positive and less VCAM-1-, Mac-1-, and VLA-4-positive inflammatory cells were detected in mucous layers of acute UC. In specimens of UC in remission, the inflammatory cells positive for the studied adhesion molecules were significantly less in number in the mucosa and submucosa (p < 0.05). Conclusions Based on the increased expression of ICAM-1, VCAM-1, and their ligands LFA-1 and VLA-4 in patients with UC, we can conclude that these adhesion molecules play a key role in the adherence of lymphocytes and macrophages to endothelial cells maintaining the chronic inflammation. Presence of E-selectin on endothelial cells of venules could be a sign of relapse after remission in UC.     

GAD65 vaccination: 5?years of follow-up in a randomised dose-escalating study in adult-onset autoimmune diabetes

Aims/hypothesis  The aim of this study was to ascertain whether treatment of GAD65 autoantibody (GADA)-positive diabetic patients with alum-formulated recombinant GAD65 (GAD-alum) is safe and does not compromise beta cell function. Methods  This Phase 2, placebo-controlled, dose-escalation clinical trial, which was randomized through a central office, was performed in 47 GADA-positive type 2 diabetic patients, who received subcutaneous injections of GAD-alum (4 [n = 9], 20 [n = 8], 100 [n = 9] or 500 [n = 8] μg) or placebo (n = 13) at weeks 1 and 4 of the trial. Participants and caregivers were blinded to group assignments. The primary outcome was safety as assessed by neurological tests, medications and beta cell function evaluated over 5 years, representing the end of the trial. Results  No severe study-related adverse events occurred during the 5 year follow-up. None of the dose groups was associated with an increased risk of starting insulin treatment compared with the placebo group. The use of oral hypoglycaemic agents did not differ between the dose groups. After 5 years, fasting C-peptide levels declined in the placebo group (−0.24; 95% CI −0.41 to −0.07 log₁₀ nmol/l; p = 0.01) and the 500 μg dose group (−0.37; 95% CI −0.57 to −0.17 log₁₀ nmol/l; p = 0.003), but not in the 4 μg (−0.10; 95% CI −0.28 to 0.07 log₁₀ nmol/l; p = 0.20), 20 μg (0.04; 95% CI −0.12 to 0.19 log₁₀ nmol/l; p = 0.58) and 100 μg (0.00; 95% CI −0.20 to −0.20 log₁₀ nmol/l; p = 0.98) dose groups. Conclusions/interpretation  The primary outcome of safety was achieved, since no severe study-related adverse events occurred. Trial registration  Because the study was initiated before 1 July 2005, the protocol was not registered in a registry. Funding  This trial was funded by the National Institutes of Health (grant numbers DK26190 and DK53004), the Swedish Research Council (grant number 72X-14064) and Diamyd Therapeutics (Stockholm, Sweden). Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorised users.