Accuracy of supplementary serologic testing for human T-lymphotropic virus types I and II in US blood donors. Retrovirus Epidemiology Donor Study

Blood donations in the United States have been screened for antibody to human T-lymphotropic virus type I (HTLV-I) by HTLV-I enzyme immunoassay (EIA) since November 1988. Specimens repeatedly found to be reactive by EIA undergo confirmation by supplementary serologic tests. We assessed the accuracy of blood center testing of 994 HTLV-I EIA repeat-reactive specimens in five US blood centers between November 1988 and December 1991. Of 410 confirmed HTLV-I/II donations, 407 (99.3%) were infected with HTLV-I/II, as determined by polymerase chain reaction (PCR) (403 cases) and by repeat serologic testing (4 cases). The three false- positive results occurred in the first year of testing. Of 425 HTLV- indeterminate specimens, 6 (1.4%) were found to be infected by PCR (5 with HTLV-II and 1 with HTLV-I). None of 159 confirmatory test-negative donations was PCR positive. Of HTLV-I/II-seropositive specimens, 80.2% to 95.4% could be typed as HTLV-I or HTLV-II by type-specific serologic assays. These results support recommendations that HTLV-I/II- seropositive donors should be advised that they are infected with HTLV- I, HTLV-II, or HTLV-I/II (depending on results of type-specific assays). HTLV-indeterminate donors should be advised that their results only rarely indicate HTLV infection. HTLV confirmatory test-negative donors should be reassured that they are not infected with HTLV-I or HTLV-II.     

Anaemia management in patients with chronic kidney disease: Taiwan practice guidelines

The introduction of erythropoiesis‐stimulating agents (ESAs) markedly improved the lives of many anaemic patients with chronic kidney disease (CKD). In Taiwan, the strategy of management of anaemia in patients with CKD was different from many other parts of the world. In 1996, the National Health Insurance Administration of Taiwan applied a more restrictive reimbursement criteria for ESA use in patients with CKD. ESA is to be initiated when non‐dialysis CKD patients have a serum creatinine >6 mg/dL and a hematocrit <28% to maintain a hematocrit level not exceeding 30%. The maximal dose of epoetin‐α or β was 20 000 U per month. The target haemoglobin range and dose limitation for ESAs were the same for dialysis CKD patients. Thus, long before randomized controlled trials showing an increased risk for cardiovascular events at nearly normal haemoglobin concentrations and higher ESA doses in CKD, nephrologists in Taiwan had avoided the use of disproportionately high dosages of ESAs to achieve a haemoglobin level of 10–11 g/dL. Moreover, intravenous iron supplementation was encouraged earlier in Taiwan in 1996, when we reached consensus on the diagnostic criteria for iron deficiency (serum ferritin <300 ng/mL and/or transferrin saturation <30%). The experience of CKD anaemia management in Taiwan demonstrated that a reasonable haemoglobin target can be achieved by using the lowest possible ESA dose and intravenous iron supplementation.     

Cytokine activation during attacks of the hyperimmunoglobulinemia D and periodic fever syndrome

The hyperimmunoglobulinemia D and periodic fever (hyper-IgD) syndrome is typified by recurrent febrile attacks with abdominal distress, joint involvement (arthralgias/arthritis), headache, skin lesions, and an elevated serum IgD level (> 100 U/mL). This familial disorder has been diagnosed in 59 patients, mainly from Europe. The pathogenesis of this febrile disorder is unknown, but attacks are joined by an acute-phase response. Because this response is considered to be mediated by cytokines, we measured the acute-phase proteins C-reactive protein (CRP) and soluble type-II phospholipase A2 (PLA2) together with circulating concentrations and ex vivo production of the proinflammatory cytokines interleukin-1 alpha (IL-1 alpha), IL-1 beta, IL-6, and tumor necrosis factor alpha (TNF alpha) and the inhibitory compounds IL-1 receptor antagonist (IL-1ra), IL-10, and the soluble TNF receptors p55 (sTNFr p55) and p75 (sTNFr p75) in 22 patients with the hyper-IgD syndrome during attacks and remission. Serum CRP and PLA2 concentrations were elevated during attacks (mean, 213 mg/L and 1,452 ng/mL, respectively) and decreased between attacks. Plasma concentrations of IL-1 alpha, IL-1 beta, or IL-10 were not increased during attacks. TNF alpha concentrations were slightly, but significantly, higher with attacks (104 v 117 pg/mL). Circulating IL-6 values increased with attacks (19.7 v 147.9 pg/mL) and correlated with CRP and PLA2 values during the febrile attacks. The values of the antiinflammatory compounds IL-1ra, sTNFr p55, and sTNFr p75 were significantly higher with attacks than between attacks, and there was a significant positive correlation between each. The ex-vivo production of TNF alpha, IL-1 beta, and IL-1ra was significantly higher with attacks, suggesting that the monocytes/macrophages were already primed in vivo to produce increased amounts of these cytokines. These findings point to an activation of the cytokine network, and this suggests that these inflammatory mediators may contribute to the symptoms of the hyper-IgD syndrome.     

Support of human cord blood progenitor cells on human stromal cell lines transformed by SV40 large T antigen under the influence of an inducible (metallothionein) promoter

We describe the development of a human bone marrow (BM) culture system which allows study of the interaction of stromal cell lines (SCL) and highly purified hematopoietic progenitor cells. Normal BM stromal cells were electroporated with a plasmid containing the simian virus 40 (SV40) large T antigen (SV40 T Ag) under the control of a synthetic metallothionein promoter (MT4); this construct is designated MT4 SV40 T Ag. SCL in which the rate of proliferation could be controlled by altering the zinc (Zn) concentration were characterized, demonstrating that the SCL were heterogeneous with respect to G-CSF and GM-CSF production. Suppression of SCL proliferation on removal of Zn made it possible to use these lines in coculture with purified CD34+ progenitor cells from umbilical cord blood. The ability to control proliferation of SCL has allowed us to maintain the survival and expansion of colony- forming cells in culture for up to 2 months. These lines have enabled us to test for stromal cell characteristics at a clonal level and provided us with a tool to analyze the events leading to lineage commitment and hematopoietic differentiation, as demonstrated by suppression of hematopoiesis by an antibody directed against the c-kit molecule.     

Administration of pegylated recombinant human megakaryocyte growth and development factor to humans stimulates the production of functional platelets that show no evidence of in vivo activation

This report describes the effect of pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) on platelet production and platelet function in humans. Subjects with advanced solid tumors received PEG-rHuMGDF daily for up to 10 days. There was no increase in circulating platelet count at doses of 0.03 or 0.1 microgram/kg/d by day 12 of study. At doses of 0.3 and 1.0 microgram/kg/d there was a threefold median increase (maximum 10-fold) in platelet count by day 16. The platelets produced in vivo in response to PEG-rHuMGDF showed unchanged aggregation and adenosine triphosphate (ATP)-release responses in in vitro assays. Tests included aggregation and release of ATP in response to adenosine diphosphate (ADP) (10, 5, 2.5, and 1.25 mumol/L), collagen (2 micrograms/mL), thrombin-receptor agonist peptide (TRAP, 10 mumol/L) and ristocetin (1.5 mg/mL). Administration of aspirin to an individual with platelet count of 1,771 x 10(3)/L resulted in the typical aspirin-induced ablation of the normal aggregation and ATP-release response to stimulation with arachidonic acid (0.5 mg/mL), collagen, and ADP (2.5 and 1.25 mumol/L). There was no change in the expression of the platelet-surface activation marker CD62P (P-selectin) nor induction of the fibrinogen binding site on glycoprotein IIb/IIIa as reported by the monoclonal antibody, D3GP3. An elevation of reticulated platelets was evident after 3 days of treatment with PEG-rHuMGDF and preceded the increase in circulating platelet count by 5 to 8 days; this reflected the production of new platelets in response to PEG-rHuMGDF. At later time points, the mean platelet volume (MPV) decreased in a manner inversely proportional to the platelet count. Levels of plasma glycocalicin, a measure of platelet turnover, rose 3 days after the initial increase in the peripheral platelet count. The level of plasma glycocalicin was proportional to the total platelet mass, suggesting that platelets generated in response to PEG-rHuMGDF were not more actively destroyed. Thus, the administration of PEG-rHuMGDF, to humans, increased the circulating platelet count and resulted in fully functional platelets, which showed no detectable increase in reactivity nor alteration in activation status.     

A case of a bleeding benign gastrocolic fistula in 2014

INTRODUCTION

In the era of proton pump inhibitors in the treatment of peptic ulcer disease, the incidence of a gastrocolic fistula arising from unoperated gastric ulcers is extremely low.

PRESENTATION OF CASE

We present the case of a 68-year old farmer who presented with melaena and was found to have a benign gastrocolic fistula in the setting of untreated peptic ulcer disease, chronic NSAID ingestion and heavy alcohol intake. The diagnosis was made by gastroscopy. En bloc surgery was undertaken due to the size of the fistula and concomitant significant bleeding of the ulcer which would not have made it amenable to medical management.

DISCUSSION

The symptoms of a gastrocolic fistula are undifferentiated and the diagnosis can easily be missed in the setting of other complications such as bleeding or perforation of a hollow viscus. Barium enamas are the most accurate for the diagnosis but gastroscopy with biopsy is usually performed to rule out malignancy. The mainstay of treatment is usually surgical, though patients can be medically managed if he/she is not a surgical candidate.

CONCLUSION

Benign gastrocolic fistulas are rare and its diagnosis is easily missed.     

Isolation of a Natural Antioxidant, Dehydrozingerone from Zingiber officinale and Synthesis of Its Analogues for Recognition of Effective Antioxidant and Antityrosinase Agents

In the present study, the antioxidative and inhibitory activity of Zingiber officinale Rosc. rhizomes-derived materials (on mushroom tyrosinase) were evaluated. The bioactive components of Z. officinale rhizomes were characterized by spectroscopic analysis as zingerone and dehydrozingerone, which exhibited potent antioxidant and tyrosinase inhibition activities. A series of substituted dehydrozingerones [(E)-4-phenyl-3-buten-2-ones] were prepared in admirable yields by the reaction of appropriate benzaldehydes with acetone and the products were evaluated in terms of variation in the dehydrozingerone structure. The synthetic analogues were examined for their antioxidant and antityrosinase activities to probe the most potent analogue. Compound 26 inhibited Fe2+-induced lipid peroxidation in rat brain homogenate with an IC50 = 6.3+/-0.4 microM. In the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical quencher assay, compounds 2, 7, 17, 26, 28, and 29 showed radical scavenging activity equal to or higher than those of the standard antioxidants, like alpha-tocopherol and ascorbic acid. Compound 27 displayed superior inhibition of tyrosinase activity relative to other examined analogues. Compounds 2, 17, and 26 exhibited non-competitive inhibition against oxidation of 3,4-dihydroxyphenylalanine (L-DOPA). From the present study, it was observed that both number and position of hydroxyl groups on aromatic ring and a double bond between C-3 and C-4 played a critical role in exerting the antioxidant and antityrosinase activity.