Phase-II trial with vindesine for regression induction in patients with leukemias and hematosarcomas

Summary Vindesine (VDS) has been submitted to a phase-II trial, the results of which were assessed in terms of regression induction. VDS was given weekly IV in doses of 2 mg/m² on two consecutive days to 59 patients, 55 of whom were evaluable. A high proportion of complete (36%) and over 50% partial regressions were obtained in acute lymphoid leukemias (ALL) (overall response 63%) whatever the perceptible phase, in blastic crisis of chronic myeloid leukemia (55%), and some responses were recorded in lymphosarcoma (40%). No effect has so far been seen in acute myeloid leukemia or in Hodgkin's disease. Malignant neoplasms of the immunoblastic type seem to be particularly sensitive to VDS. Continuous 48 h IV infusion can induce a remission where an IV push administration of the same dose has failed. One remarkable characteristic of VDS is the apparent absence of cross-resistance with VCR: in acute leukemic forms, 55% of patients who failed to obtain remission induction after three weekly injections of VCR (used in combination chemotherapy) achieved a complete or partial remission with VDS. The toxicity was mainly neurologic (paralytic ileus, constipation, paresthesias, loss of reflexes) and hematologic (leukopenia and thrombopenia), and was not more significant than with the other agents: four patients died of infection or hemorrhage.     

Human alphavbeta3 integrin potency and specificity of TA138 and its DOTA conjugated form (89)Y-TA138

The present study was undertaken to define the alphavbeta3-binding potency and specificity of TA138, a nonpeptide integrin antagonist, and its conjugated form, 89Y-TA138. Various integrin-specific binding and functional assays as well as cell-adhesion assays were used to determine the potency and integrin specificity for TA138 and 89Y-TA138. Both TA138 and 89Y-TA138 inhibited alphavbeta3-mediated [125I]echistatin binding to 293-beta3-transfected cells, with IC50 values of 0.046 and 0.059 microM, respectively, and IC50 values of 0.012 and 0.018 microM, respectively, in inhibiting an alphavbeta3 integrin-mediated 293-beta3-transfected cell adhesion to fibrinogen. TA138 inhibited human umbilical vein endothelial cell adhesion to fibrinogen, with an IC50 value of 0.052 +/- 0.006 microM. Both TA138 and 89Y-TA138 demonstrated a relatively high degree of specificity for human alphavbeta3 integrin as compared with other human integrins, including alphavbeta5, alphaIIbbeta3, and alpha5beta1 (IC50 > 10 microM). Both 89Y-TA138 and TA138 demonstrated comparable alphavbeta3 affinity and specificity as compared with other closely related human integrins such as alphavbeta5, alphaIIbbeta3, or alpha5beta1.     

Cardiac echinococcosis: echocardiographic diagnosis with a fatal clinical outcome

Hydatid disease HD is an endemic disease found in various regions of the world. The organs mostly affected are the liver and lung. Cardiac involvement in HD is rare. The symptoms are mainly due to the mass effect of the calcific hydatid cyst obstructing the blood or the lymphatic vessels. Other manifestations are secondary infection or cyst rupture in the involved organ. Here, we report a middle aged female patient with no history of medical illness who presented to the emergency room with an unrecordable blood pressure. Echocardiogram showed multiple calcific cysts of echinococcosis granulosa in the left ventricle cavity. In the clinical setting, where there is detection of HD elsewhere in the body, an echocardiogram is mandatory as cardiac involvement is serious and may be fatal.     

Cutaneous vasculitis

Vasculitis is defined as inflammation of blood vessels and can affect multiple organs. Several classification systems exist to categorize vasculitis such as vessel size, presence of anti-neutrophil cytoplasmic antibody, pathogenesis of the inflammation, and type of inflammatory cell infiltrate. Cutaneous vasculitis occurs as a manifestation of many diseases including rheumatologic diseases, hypersensitivity syndromes, infections, and malignancies. The diagnosis of the cutaneous vasculitis and the underlying cause requires a complete history and physical exam and usually a biopsy or angiogram. The treatment depends on the etiology of the inflammation and includes immunosuppression, withdrawal of the offending agent, antibacterial/antiviral agents, and chemotherapies. A clear understanding and approach to this condition will improve the physician’s ability to provide optimal patient care.     

Fungus-infected fluid collections in thorax or abdomen: effectiveness of percutaneous catheter drainage

PURPOSE: To retrospectively evaluate the effectiveness of percutaneous catheter drainage in the treatment of fungus-infected fluid collections in the thorax or abdomen and to identify any factor that may be predictive of a poor clinical outcome. MATERIALS AND METHODS: Approval for this study was obtained from the hospital ethics subcommittee on human studies. Because the study was retrospective, patient informed consent was not required. This study was compliant with the Health Insurance Portability and Accountability Act. Retrospective analysis was performed of cases of fungus-infected fluid collections in the thorax or abdomen treated by using percutaneous catheter drainage in 60 patients (36 male and 24 female patients; mean age, 57 years; range, 2 months to 91 years) during 5 years. The patient medical records were reviewed to identify recognized factors for predisposition to fungal infection. The details of percutaneous catheter drainage and microbiologic findings were recorded. The technical success (ability of catheters placed to drain collections treated) and the clinical success (ability of patients to recover fully without surgery) of percutaneous catheter drainage were determined. A multifactor logistic regression analysis was performed to identify any clinical or microbiologic factor predictive of a poor clinical outcome. RESULTS: Seventy-three fungus-infected fluid collections were drained in 60 patients. The collections originated from the pleura (n = 6), mediastinum (n = 2), liver (n = 3), pancreas (n = 5), obstructed biliary or urinary tract (n = 9), gallbladder (n = 1), and abdominopelvic area (n = 47). The technical success rate for catheter drainage was 79% (41 of 52 patients); the clinical success rate, 57% (34 of 60 patients). Twenty (33%) patients died from all causes during hospital admission. Multifactor logistic regression analysis was used to identify predictors of a poor clinical outcome; complexity of collection, history of malignancy, and admission to intensive care unit were significant (P < .03) and independent predictors. CONCLUSION: Despite a moderately high technical success rate with percutaneous catheter drainage of fungus-infected fluid collections, clinical success rate was much lower. Both imaging appearance (complexity of collection) and clinical factors (history of malignancy, admission to intensive care unit) influenced prognosis.     

Periodontal diseases and the risk of coronary heart and cerebrovascular diseases: a meta-analysis

BACKGROUND: This meta-analysis was conducted to examine the relationship between periodontal diseases and coronary heart diseases (CHD) and cerebrovascular diseases (CVD) in observational studies. METHODS: This study was based on seven cohort studies and four studies of other designs that met prestated inclusion criteria. Information on study design, year of publication, study location, sample size, study population, participant characteristics, measurement of risk factors, exposure and outcome measures, matching, controlling for confounders, and risk estimates was abstracted independently by two investigators using a standard protocol. RESULTS: Subjects with periodontitis had an overall adjusted risk of CHD that was 1.15 times (95% confidence interval [CI]: 1.06 to 1.25; P = 0.001) the risk for healthy subjects. There was no heterogeneity among the studies in the overall relative risk estimate (P = 0.472). As compared to healthy subjects, those with periodontitis had an overall adjusted relative risk of CVD of 1.13 (95% CI: 1.01 to 1.27; P = 0.032). CONCLUSIONS: Findings indicated that periodontal infection increases the risk of CHD and CVD. However, this meta-analysis provided no evidence for the existence of strong associations between periodontitis and CHD and CVD. Larger and better-controlled studies involving socially homogeneous populations and measuring specific periodontal pathogens are required to identify a definite association between periodontal disease and the risk of coronary heart disease and cerebrovascular disease.     

Alpha-interferon with ribavirin in the treatment of hemodialysis patients with hepatitis C

INTRODUCTION: Hepatitis C Viral (HCV) infection is the leading cause of chronic liver disease in end-stage renal disease patients (ESRD). The impact of HCV on patient and graft survival posttransplantation is controversial. The most successful approach is to eliminate the virus while the patient is on dialysis prior to transplantation. The main aim of this pilot study was to assess the efficacy of combined alpha-interferon (alpha-IFN) and ribavirin treatment of HCV hemodialysis (HDx) patients, by comparing the sustained virological response to that obtained by local historical data on treatment with alpha-IFN alone. A secondary aim was to establish the optimal therapeutic dose of ribavirin in this regimen. METHODS: Twenty HCV-HDx patients who were histologically (liver biopsy) and virologically (HCV-PCR)-positive were selected randomly. They received combination therapy with 3 million units (MU) of alpha-IFN and 200 mg of ribavirin three times a week. Initially nine patients were treated for 24 weeks. Later, another 11 patients were randomly selected to give the combination for 48 weeks. RESULTS: Six of the nine patients who were treated for 24 weeks (66%) became HCV-PCR-negative by the end of the treatment period. They continued to have a sustain virologic response at 6 months after the cessation of therapy. Six of the 11 patients (55%) who were treated for 48 weeks became HCV-PCR-negative at the end, and at 6 months after cessation of treatment. Of the first six responders, 4 (66%) maintained a sustained virologic response at 1 year postcessation of therapy. Nine of the 11 patients had genotype 4 and 1. No side effects were reported for a ribavirin dose of 200 mg three times a week. CONCLUSION: This pilot study suggests that combination treatment for 24 weeks and 48 weeks with 3 MU alpha-IFN and 200 mg ribavirin three times a week, elicited a sustained virologic response in HDx patients with HCV infection better than IFN alone with minimal side effects. A prospective, double-blind, controlled study using pegylated INF plus ribavirin is currently underway.