Disodium cromoglycate in the treatment of ulcerative colitis and Crohn''s disease

A controlled clinical study on disodium cromoglycate (DSCG) at a dose of 800 mg per day versus placebo was carried out in 141 patients with ulcerative colitis and 25 patients with Crohn's disease. Those of the ulcerative colitis patients who had been on sulphasalazine treatment continued that treatment during the trial (101 patients). Forty patients were intolerant of sulphasalazine. No patient received steroids during the last month before the study. Patients with Crohn's disease had their possible sulphasalazine treatment stopped before the trial. No beneficial effect of DSCG as compared with placebo was found, as the DSCG and the placebo group showed the same number of relapses in patients with a clinically inactive ulcerative colitis at the start of the trial and the same number of patients improving, deteriorating, and maintaining steady state in patients with clinically active ulcerative colitis at the start of the trial. There was no difference between relapse rate in DSCG and placebo groups in patients with Crohn's disease. No correlation between the eosinophil count in rectal mucosa and the outcome of the attack of ulcerative colitis could be demonstrated.     

Association between systemic lupus erythematosus and Helicobacter pylori seronegativity

OBJECTIVE: Helicobacter pylori is a gram negative spiral bacterium that is clearly associated with a variety of gastrointestinal pathologies. A number of non-gastrointestinal diseases have also been associated with H. pylori. We investigated the prevalence of H. pylori seropositivity as part of a larger serologic survey in a group of 466 patients with systemic lupus erythematosus (SLE) and 466 controls. METHODS: We studied subjects for seropositivity against 5 antigens including mumps, measles, rubella, varicella zoster, and H. pylori. The 466 SLE patients were taken from a total of 290 pedigrees multiplex for SLE and matched to 466 controls for age (+/- 3 yrs), sex, and ethnicity to non-SLE affected individuals, taken mostly from the same collection of pedigrees multiplex for SLE. Assays for seropositivity were performed using a heterogeneous immunoassay technique. Pearson's chi-square was used to test for association of categorical variables and Student t-test for continuous variables. Logistic regression was used to compute the odds ratio for H. pylori seropositivity in patients and controls. RESULTS: There was a significant difference only in H. pylori seropositivity between SLE cases and their controls. The results were not altered by intrafamilial correlation. Subset analysis by race and sex showed that the differences between the African-American female patients with SLE and their matched controls were responsible for this association. Female African-American patients with SLE had a lower prevalence of H. pylori seropositivity compared to controls (38.1% vs 60.2%, OR 0.41, p = 0.0009, 95% CI 0.24-0.69). Of the 113 African-American female SLE patients in the study group, 43 were seropositive for H. pylori. The mean age of onset for SLE was older in the seropositive group (34.4 yrs) compared to the seronegative SLE patients (28.0 yrs) (t = 2.11, p = 0.039). CONCLUSION: Of 5 serologic tests performed, only the frequency of H. pylori seropositivity was different between SLE cases and their controls, and then only in African-Americans. We found an association between being seronegative for H. pylori and the development of SLE in African-American women, who also tend to be younger at the time of disease onset. These findings suggest that there is a possible protective role for H. pylori infection against the development of SLE or that immunoregulatory events leading to H. pylori seropositivity are inversely related to the risk of SLE.     

Accuracy of urine urobilinogen and bilirubin assays in predicting liver function test abnormalities

Components of the dipstick urinalysis (urine urobilinogen and urine bilirubin) are often used by emergency physicians to screen for the need to obtain liver function tests in many clinical situations. A prospective observational study was conducted to evaluate the sensitivity, specificity, and predictive properties of spot urine bilirubin and urobilinogen assays in the emergency department as screening test for serum liver function test (LFT) abnormalities. Of 122 patients, abdominal pain was the indication for laboratory evaluation in 54%; jaundice and constitutional symptoms were the indication in 29%. Overall sensitivities for both urine assays were 70% to 74% for serum bilirubin, but 43% to 53% for other LFTs; specificities were 77% to 87% for both urine screens. Positive predictive values show that the urine assays were 83% to 86% reliable for detecting at least one LFT abnormality. Negative predictive values were 85% for both urine assays for serum bilirubin elevations, but lower for other LFTs. Urine urobilinogen has its greatest clinical utility as a screen when a normal/abnormal threshold of 2.0/4.0 mg/dL is used.     

CFU-GM content of bone marrow graft correlates with time to hematologic reconstitution following autologous bone marrow transplantation with 4- hydroperoxycyclophosphamide-purged bone marrow

Autologous bone marrow transplants (BMTs) can repopulate the hematologic system of patients treated with marrow-ablative chemotherapy and/or radiotherapy. However, treatment of the bone marrow graft to eliminate residual tumor cells prior to reinfusion can delay the return of peripheral blood elements, presumably from damage to or loss of hematopoietic stem cells responsible for hematologic recovery. To develop a model predictive of hematologic recovery, we studied the progenitor cell contents of 4-hydroperoxycyclophosphamide (100 micrograms/mL)-purged bone marrow grafts of 40 consecutive patients undergoing autologous BMT at this center. Granulocyte-macrophage colonies (CFU-GM) were grown from all grafts after treatment with this chemotherapeutic agent, but erythroid (BFU-E) and mixed (CFU-GEMM) colonies were grown from only 44% and 33% of the grafts respectively. The recovery of CFU-GM after purging ranged from 0.07% to 23%. The logarithm of CFU-GM content of the treated grafts was linearly correlated with the time to recovery of peripheral blood leukocytes (r = -0.80), neutrophils (r = -0.79), reticulocytes (r = -0.60), and platelets (r = -0.66). The CFU-GM content of purged autologous bone marrow grafts may reflect the hematopoietic stem cell content of the grafts and thus predict the rate of hematologic recovery in patients undergoing autologous BMT.     

LDIflare small fiber function in normal glucose tolerant subjects with and without hypertriglyceridemia

Introduction: We explored determinants of small fiber function (SFF) in normoglycemic individuals to determine influence of metabolic parameters, including triglyceride (TG) levels. Methods: Dorsal foot SFF was assessed by the LDIflare method in 79 individuals without clinical neuropathy, including 43 controls (HC, <1.7 mmol/L), 17 with mild hypertriglyceridemia (MiTG, 1.7–2.25), and 19 with significant hypertriglyceridemia (HiTG, >2.25 mmol/L). Results: LDIflare was significantly smaller in HiTG compared with HC (4.4 ± 1.4 vs. 9.3 ± 2.9 cm²; P < 0.0001) and compared with the MiTG (4.4 ± 1.4 vs. 7.0 ± 2.1; P < 0.0001). Over all, an inverse correlation existed between LDIflare and age (?0.42; P < 0.0001), weight (r = ?0.37; P = 0.004), body mass index (BMI) (?0.51; P < 0.0001), Log₁₀ triglycerides (r = ?0.66; P < 0.0001), total cholesterol (r = ?0.26; P = 0.02), and TC/HDL ratio (r = ?0.40; P = 0.002). In multivariate regression analysis, Log₁₀ triglycerides (P < 0.0001) and age (P = 0.003) were the only independent predictors. Conclusions: There is an inverse correlation between small fiber function and triglycerides in normoglycemic individuals and abnormal SFF in normoglycemic hypertriglyceridemia. Larger prospective studies are required to confirm these findings and to determine whether reduced SFF heralds later clinical neuropathy. Muscle Nerve 52 : 113–119, 2015     

Galanin is an autocrine myelin and oligodendrocyte trophic signal induced by leukemia inhibitory factor

In order to further investigate the molecular mechanisms that regulate oligodendrocyte (OC) survival, we utilized microarrays to characterize changes in OC gene expression after exposure to the cytokines neurotrophin3, insulin, or leukemia inhibitory factor (LIF) in vitro. We identified and validated the induction and secretion of the neuropeptide galanin in OCs, specifically in response to LIF. We next established that galanin is an OC survival factor and showed that autocrine or paracrine galanin secretion mediates LIF‐induced OC survival in vitro. We also revealed that galanin is up‐regulated in OCs in the cuprizone model of central demyelination, and that oligodendroglial galanin expression is significantly regulated by endogenous LIF in this context. We also showed that knock‐out of galanin reduces OC survival and exacerbates callosal demyelination in the cuprizone model. These findings suggest a potential role for the use of galanin agonists in the treatment of human demyelinating diseases. GLIA 2015;63:1005–1020     

Predictors of early response to initial therapy in patients with newly diagnosed symptomatic multiple myeloma

Response to therapy in newly diagnosed symptomatic multiple myeloma (NDMM) can impact long‐term outcomes. It is not clear if baseline laboratory parameters can predict an early, deep response. Totally 1,304 patients with NDMM seen between 2001 and 2013 at Mayo Clinic Rochester were studied. The association between baseline laboratory parameters and early, deep response defined as a very good partial response or better (VGPR+) within four cycles of treatment was investigated. Multivariable logistic regression was used to assess the associations between the parameters of interest and response. Multivariable proportional hazards regression was used to assess the association between response and overall survival. In the entire cohort, greater absolute free light chain (FLC) differences (OR 2.38, 95% CI 1.48–3.82), younger age (OR 2.18, 95% CI 1.28–3.71), lower hemoglobin (OR 1.68, 95% CI 1.12–2.54), and IgA myeloma (OR 1.66, 95% CI 1.10–2.51) were associated with increased odds of achieving VGPR+ after four cycles. Among patients receiving novel agents in general and immunomodulators in particular, these effects were more pronounced. In patients receiving proteasome‐inhibitors, higher creatinine (OR 3.83, 95% CI 1.37–10.1), lower calcium (OR 3.37, 95% CI 1.36–8.35), and greater absolute FLC differences (OR 2.50, 95% CI 1.10–5.71) were associated with better response. In a landmark analysis at 4 months from diagnosis, achieving VGPR+ was associated with decreased risk of subsequent mortality (HR 0.69, 95% CI 0.53–0.86). In summary, several parameters were associated with an early, deep response to treatment, revealing distinct sets of predictors for immunomodulator‐ and proteasome‐inhibitor‐containing regimens. Achieving VGPR+ after four cycles translated into increased overall survival. Am. J. Hematol. 90:888–891, 2015. © 2015 Wiley Periodicals, Inc.