Plasma protein oxidation is associated with an increase of procoagulant markers causing an imbalance between pro- and anticoagulant pathways in healthy subjects

The aim of the present study was to investigate whether the overall oxidation state of plasma proteins is associated with changes of circulating pro- and anticoagulant markers in healthy subjects (n = 99, 49 males, 50 females, aged from 6 to 91 yrs.). The carbonyl content of plasma proteins was measured and validated as an ex vivo index of the overall protein oxidation state due to its correlation with the plasma level of o-tyrosine (r = 0.87, P <0.0001), which is a well known oxidized product of L-phenylalanine. Using a multivariate analysis the carbonyl content of plasma protein was positively associated with procoagulant markers such as prothrombin F1 + 2 (r = 0.28, P = 0.0019) and fibrinopeptide A, (FpA) (r = 0.278, P = 0.003), as well as with the soluble derivative of the endothelial protein thrombomodulin (TM) (r = 0.469, P <0.0001). The procoagulant marker of thrombin activity, FpA, was significantly and positively correlated with the anticoagulant product of thrombin, namely the Protein C activation peptide (PCP), only in the tertile with low protein carbonyl content. At higher tertiles this correlation was no longer observed, thus suggesting a detrimental effect of oxidative stress on the TM/Protein C anticoagulant pathway. In 15 subjects with high carbonyl content of plasma protein, treatment for 18 days with 600 mg/d of vitamin E did not substantially modify the protein carbonyl content, the anticoagulant markers APC/PCP, and all procoagulant markers except F1+2, whose value significantly decreased by 25%. In conclusion, the present study shows that a high plasma protein oxidation ex vivo is associated with an overall hemostatic imbalance, which favors procoagulant markers. Vitamin E treatment in vivo restores only in part the equilibrium between pro- and anticoagulant pathways. This may open the way to further studies aimed at elucidating the mechanisms by which the oxidative stress is linked to activation of the coagulation system in atherothrombotic disorders.     

Lymphoma of the cecum: a case report

Non-Hodgkin lymphomas present a wider systemic diffusion than Hodgkin lymphomas. Superficial and internal nodes, the tracheobronchial tree, and the digestive tract are almost always affected. The gastrointestinal tract is affected in 50% of the cases; the stomach is the first organ, followed by the small intestine and large intestine. The colon is affected in only approximately 0.4% of cases. The clinical picture of our patient showed abdominal pain, palpable mass, and anemia. Colonoscopy showed a tumor in the cecum (diameter, approximately 10 cm) and the biopsy indicated lymphoma. Through computed tomography, bone marrow biopsy, and measurement of beta2-microglobulin, complete staging was obtained. Right hemicolectomy was immediately performed because the large tumor could determine intestinal occlusion. Definitive diagnosis was non-Hodgkin lymphoma, type mucosa-associated lymphatic tissue B cells with a low grade of malignancy. After surgery the patient underwent six courses of chemotherapy according to the CHOP scheme (750 mg/m2 cyclophosphamide, 1.4 mg/m2 vincristine, 50 mg/m2 adriamicin, and 80 mg prednisone). Two years after surgery the patient shows no sign of the disease.     

High-dose cytarabine as consolidation treatment for patients with acute myeloid leukemia with t(8;21)

Seventeen patients affected by acute myeloid leukemia (AML) with t(8;21) were prospectively programmed to receive three courses of high-dose cytarabine (HDARA-C) as post-remission therapy. The median age was 39 years and in all cases t(8;21) was the only karyotypic abnormality. Complete remission (CR) was achieved in 14 out of 17 cases (82%) and, after first consolidation with NOVIA regimen (intermediate dose ARA-C plus mitoxantrone), all patients received the three planned courses of HDARA-C (3g/m(2) q12h on days 1, 3, 5). There were two documented infections, while all patients experienced fever of unknown origin (FUO). Nonhematological toxicity was mild. Thirteen out of 14 patients are in continuous CR after a median follow-up of 44 months. One patient relapsed at 16 months and, following CR2 achievement, underwent allogeneic transplantation; he died 3 months later while in CR from acute graft versus host disease (GVHD). Survival at 5 years is projected at 79%. Our data confirm the efficacy of repeated courses of HDARAC for patients with t(8;21) AML.     

Tamoxifen is not effective in good prognosis patients with hepatocellular carcinoma

Background  

Large randomised clinical trials and systematic reviews substantiate that tamoxifen is ineffective in improving survival of patients with hepatocellular carcinoma (HCC). However, a recent report suggested that the drug might prolong survival among patients with well preserved liver function. The aim of this paper is to validate this hypothesis.     

Dietary therapy in diabetic pregnancy: recommendations

As a further elaboration of our systematic definition of nutritional therapy in diabetic patients, this booklet looks at the delicate but very important question of the diabetic woman’s diet during pregnancy. The recommendations were drafted by diabetologists and nutritionists who have specifically studied the problems of nutrition in pregnancy, and are backed by the Italian Association for Clinical Dietetics and Nutrition (ADI), the Association of Medical Diabetologists (AMD), and the Italian Society for Diabetology (SID). The synergism of this joint effort has produced a document that we sincerely hope will help all members of teams who tackle this vital issue in diabetes in their daily work.     

High incidence of monoclonal EBV episomes in Hodgkin's disease and anaplastic large-cell ki-1-positive lymphomas in HIV-1-positive patients

A series of selected lymphoid malignancies (LMs) occurring in Italian HIV-1-infected (HIV⁺) patients, principally intravenous drug users, was investigated. In addition to small non-cleaved-cell (SNCC) and large-cell immunoblastic (LCI) non-Hodgkin's lymphomas (NHLs), a relatively high occurrence of anaplastic large-cell Ki-1-positive (ALC Ki-1⁺) lymphomas and Hodgkin's disease (HD) was observed, at variance with other reported series of HIV⁺ patients. Combined results of in situ hybridization and Southern-blot analyses, in conjunction with immunohisto-chemical detection of Epstein-Barr virus (EBV)-encoded latent membrane protein-1 (LMP-1), showed an almost complete association of ALC Ki-1⁺ lymphomas and HD cases with EBV. The neoplastic cells of both these LMs also showed common immunophenotypic features such as frequent absence of B- and T-cell differentiation markers and expression of the Ki-1 activation marker, while SNCC and LCI lymphomas were mainly of mature B-cell origin and Ki-1^-. The concomitant high incidence of ALC Ki-1⁺ lymphomas and HD in a specific group of HIV⁺ patients, their almost complete association with EBV in clonal and episomal form and the great similarity in differentiation, activation and virological markers which they display suggest that these LMs are pathological variants of a continuous spectrum of HIV-1-associated disorders etiopathologically linked to EBV.     

A seroepidemiological study of toxoplasma gondii infection in children of northern Greece

The aims of this study were to determine the incidence of toxoplasmosis in children ofthe northern Greece region through the evaluation of serologic examination. Sera of 486 children, aged between 6 months and 15 years, suffering from different clinical entities, were tested for anti-Toxoplasma gondii specific IgG antibodies, using an ELISA (enzyme linked immunosorbent assay) technique. In this survey, a high percentage (11.1 percent) of the hospitalized children reacted positively to this method. Males and females had equal prevalence, 11 percent and 11.2 percent, respectively. Seropositivity rate was higher in children aged between 6 and 10 years old. In conclusion, our results indicate toxoplasma infection is an important public health problem affecting children and adolescents in northern Greece. We believe that the study described here could be considered for inclusion in existing national screening programs for hospitalized children.     

An outbreak of Salmonella hadar associated with food consumption at a building site canteen

A biphasic outbreak of gastroenteritis caused by Salmonella hadar affected canteen employees and workers at a construction site in central Italy in September 1994. There were 448 symptomatic cases, from 61 of whom group C Salmonella was isolated. Six cases were canteen employees. Twenty-two other individuals were asymptomatic excreters. There were 10 secondary cases. Working as a food handler at the canteen constituted an increased risk of infection, independently of ingestion of the food (odds ratio: 62.1; 95% confidence interval (CI): 9.5– 406.6). Having eaten at the canteen on the 19th and 20th September was identified as risk factor for subjects symptomatic within 72 hours (relative risk (RR): 17.0, 95% CI: 2.3–124.3), and cooled meat salad was identified as the vehicle of infection (RR: 36.6, 95% CI: 14.3–93.8). The use of portable toilets was another possible route of transmission of infection for all cases (RR: 1.3, 95% CI: 1.0–1.6). The index case was a cook who had symptoms five days before the peak of the outbreak. From 27 individuals both symptomatic and asymptomatic excreters group B, group D and not-typed Salmonellas were isolated. This study underlines the problem of improper food handling in salmonellosis outbreaks and emphasizes the role of several vehicles in the transmission of salmonellosis in a community.     

Prophylactic fenoldopam for renal protection in sepsis: a randomized, double-blind, placebo-controlled pilot trial

OBJECTIVE: Acute renal failure is common in septic patients. Fenoldopam, a dopamine-1 receptor agonist, increases renal blood flow and may, therefore, reduce the risk of acute renal failure in such patients. Accordingly, we sought to determine the safety and efficacy of fenoldopam for the prevention of acute renal failure in septic patients. DESIGN: Prospective, double-blind, placebo-controlled trial. SETTING: Three multidisciplinary intensive care units at a university hospital. PATIENTS: Three hundred septic patients with baseline serum creatinine concentrations <150 micromol/L. INTERVENTIONS: We randomized patients to a continuous infusion of either fenoldopam (n = 150) at 0.09 microg x kg x min or placebo (n = 150) while in the intensive care unit. The primary outcome measure was the incidence of acute renal failure, defined as a serum creatinine concentration increase to >150 micromol/L, during study drug infusion. MEASUREMENTS AND MAIN RESULTS: The incidence of acute renal failure was significantly lower in the fenoldopam group compared with the control group (29 vs. 51 patients; p = .006). The odds ratio of developing acute renal failure for patients treated with fenoldopam was estimated to be 0.47 (p = .005). The difference in the incidence of severe acute renal failure (creatinine >300 mumol/L), however, failed to achieve statistical significance (10 vs. 21; p = .056). The length of intensive care unit stay in surviving patients was significantly lower in the fenoldopam group compared with the control group (10.64 +/- 9.3 vs. 13.4 +/- 14.0; p < .001). There were no complications of fenoldopam infusion. A direct effect of treatment on the probability of death, beyond its effect on acute renal failure, was not significant (odds ratio = 0.68, p = .1). CONCLUSIONS: Compared with placebo, low-dose fenoldopam resulted in a smaller increase in serum creatinine in septic patients. The clinical significance of this finding is uncertain. A large multiple-center trial is now needed to confirm these findings.