A prospective randomized controlled clinical trial of zoledronic acid for bone metastases

In this study, we assessed the safety, tolerability, and effectiveness of two therapeutic regimens relating to the frequency of zoledronic acid (ZOL) infusion. Sixty adult patients with bone metastases were randomly assigned to two study groups. The first group (group A) received 4 mg ZOL every two weeks, and the second group (group B) received 4 mg ZOL every four weeks. Assessment measures included C-telopeptide (CTX) rate, the Greek Brief Pain Inventory (GBPI), the linear analogue scale assessment (LASA) of quality of life, and biochemical markers. Assessments were made at weeks 12, 24, 36, and 48. Clinical endpoints included effective decrease in bone resorption markers, pain relief and improvement of mobility status. The follow-up period was 48 weeks. No statistically significant differences between groups A and B were found in overall profile of biochemical markers, Eastern Cooperative Oncology Group (ECOG) performance status, and GBPI score at the end of the follow-up period. Assessment of bone metastases revealed a slight difference between the two groups, however this difference was not statistically significant. These findings indicate that administering zoledronic acid at four rather that two weeks has no significant impact on overall outcome.     

Salvage chemotherapy with gemcitabine and oxaliplatin in heavily pretreated patients with metastatic breast cancer: a multicenter phase II study

PURPOSE: It was the aim of this study to evaluate the activity and tolerance of gemcitabine and oxaliplatin in pretreated metastatic breast cancer patients. METHODS: Thirty-one patients who had disease relapse or progression after completion of an anthracycline- and/or taxane-based front-line regimen were treated with gemcitabine 1,500 mg/m(2) on days 1 and 8 as a 30-min intravenous infusion and oxaliplatin 130 mg/m(2) on day 8 as a 4-hour intravenous infusion, in cycles of 21 days. RESULTS: Complete response occurred in 1 patient (3%) and partial response in 4 patients (13%) (overall response rate 16%; 95% confidence interval 3.2-29.1). Nine patients (29%) had stable disease and 17 (55%) progressive disease. Three partial responses (13%) were achieved among 23 patients receiving the regimen as third-line treatment. The median duration of response was 6 months (range 3-44.8), the median time to tumor progression 4.6 months (range 0.8-43.8), and the median survival 14.4 months (range 2.1-44.8). Grade 3 and 4 neutropenia occurred in 14 patients (45%), grade 3 and 4 thrombocytopenia in 6 patients (20%), and grade 2 and 3 asthenia in 4 patients (13%). There was no episode of febrile neutropenia. CONCLUSION: The gemcitabine-oxaliplatin combination is a relatively active and well-tolerated salvage regimen in patients with heavily pretreated metastatic breast cancer.     

Use of avidin-biotin-glucose oxidase complex to detect antimalarial antibody in serum by light microscopy

An immunohistochemical assay was developed combining an avidin-biotin-glucose oxidase complex procedure (ABC-GO) with light microscopy to detect specific antibody against Plasmodium falciparum. Thin blood films were prepared from culture material of P. falciparum and fixed with acetone. Antibody was detected by successive incubations with test serum, biotinylated goat antihuman antibody, avidin-biotin-glucose oxidase complex, and glucose oxidase substrate. In the presence of reactive serum, a blue precipitate formed on the parasites and could be visually observed with a 40x objective. Sera from patients with single infections for P. vivax or P. ovale were unreactive. No cross-reactivity was observed with sera from patients with rheumatoid arthritis, filariasis, amebiasis, schistosomiasis, dengue, scrub typhus, leptospirosis, or toxoplasmosis. The sensitivity of ABC-GO is comparable to that of the indirect fluorescent antibody test.     

Suitability of caspofungin for aerosol delivery: physicochemical profiling and nebulizer choice

BACKGROUND: Aerosolized antifungal therapy is a promising route of drug delivery for pulmonary aspergillosis due to attainment of high localized concentrations. Caspofungin, a new antifungal agent with proven efficacy against invasive aspergillosis, has ideal potential for aerosolization. STUDY OBJECTIVE: To examine in vitro the suitability of caspofungin for aerosol administration by characterizing factors that influence efficacy and airway tolerance of aerosol delivery: physicochemical properties, aerodynamics of drug particles, and efficiency of nebulizing systems. DESIGN: Physicochemical characteristics of caspofungin solutions (10 mg/mL and 30 mg/mL) were analyzed: osmolality, pH, viscosity, and surface tension. A time-of-flight aerosol spectrometer API Aerosizer was used to determine aerosol particle size and distribution. Drug output was quantified by high-performance liquid chromatography assay. Nebulizer efficiency was measured by drug output and respirable fraction (percentage of aerosolized particles with a 1 to 5 mum aerodynamic diameter) and compared among three jet nebulizer/compressor systems: device 1, Micromist (Hudson RCI; Temecula, CA)/Pulmo-Aide (model 5650D; DeVilbiss; Somerset, PA); device 2, Sidestream MS 2400/Envoy model IRC 1192 (Invacare; Elyria, OH); and device 3, Pari LC Star/Proneb Ultra (Pari Respiratory Equipment; Midlothian, VA). MEASUREMENTS AND RESULTS: Caspofungin requires 0.9% NaCl rather than sterile water as the diluent and addition of 0.3N NaOH buffer to adjust acidity of solutions (pH 6.17 to 6.26) in order to achieve optimal physicochemical properties for airway tolerability (osmolality, 150 to 550 milliosmol per kilogram; chloride ion, 31 to 300 mmol/L; and pH 7.4). The drug output rate increased with higher concentrations of drug solution: device 1, 4.0 mg/min vs 12.5 mg/min; device 2, 5.4 mg/min vs 14.7 mg/min; and device 3, 2.3 mg/min vs 12 mg/min, respectively. The percentage of particles within the respirable range varies depending on device and concentration of drug solutions (10 mg/mL vs 30 mg/mL): device 1, 85% vs 38%; device 2, 44% vs 57%; and device 3, 83% vs 93%, respectively. CONCLUSION: Caspofungin solution with adjustments appears to have physicochemical and aerodynamic characteristics suitable for aerosolization when used with either the Pari LC Star/Proneb Ultra or Micromist/Pulmo-Aide devices. Further in vivo testing is warranted.     

Clarithromycin co-administered with amikacin attenuates systemic inflammation in experimental sepsis with Escherichia coli

To assess the efficacy of clarithromycin as an immunomodulator in experimental sepsis with Escherichia coli, acute pyelonephritis was induced after ligation of the right ureter and injection of the test isolate into the renal pelvis in 40 rabbits. Four groups of treatment were applied with administration of therapy on advent of sepsis-associated pulmonary oedema, as follows: A: controls; B: clarithromycin; C: amikacin, D: both agents. Survival was recorded along with estimation of serum levels of endotoxins (LPS), of tumour necrosis factor-alpha (TNFalpha), malondialdehyde (MDA) and of bacterial counts. Mean survival of groups A, B, C and D was 2.51, 7.60, 10.25 and 11.40 days, respectively. Serum levels of TNFalpha and of MDA of group A increased over-time. Pulmonary oedema at 6 h after bacterial challenge was accompanied by increase of TNFalpha and MDA; administration of clarithromycin decreased their values. It is concluded that intravenous clarithromycin might constitute a promising immunomodulatory agent for the management of sepsis since its efficacy was proved after administration on presentation of sepsis-associated pulmonary oedema. The presented findings emphasise the need for further clinical research of the use of clarithromycin for the therapy of Gram-negative sepsis.     

Meta-analysis of the randomized controlled trials of the hemostatic efficacy and capacity of pathogen-reduced platelets

BACKGROUND: A recent independently funded randomized controlled trial (RCT; Br J Haematol 2010;150:209‐17) questioned prevailing opinion concerning the hemostatic capacity of pathogen‐reduced platelets (PLTs). Meta‐analysis was used to calculate the effect of pathogen reduction (PR) of PLTs on hemostatic efficacy and capacity based on all available data and to investigate possible reasons for the variation in reported findings. STUDY DESIGN AND METHODS: RCTs allocating patients to receive routine PLT transfusions with pathogen‐reduced or untreated PLTs and reporting on at least one of six hemostasis endpoints were eligible for analysis. Five RCTs of hemato‐oncology patients met eligibility criteria. Endpoints determined by similar criteria in all RCTs were integrated by fixed‐effects methods. Endpoints determined by different criteria were integrated by random‐effects methods. RESULTS: Studies were statistically homogeneous in all analyses. Pathogen‐reduced PLTs were associated with a significant (p < 0.05) reduction in 1‐ and 24‐hour posttransfusion corrected count increments (summary mean difference, 3260; 95% confidence interval [CI], 2450‐4791; and summary mean difference, 3315; 95% CI, 2027‐4603) as well as a significant increase in all and in clinically significant bleeding complications (summary odds ratio [OR], 1.58; 95% CI, 1.11‐2.26; and summary OR, 1.54; 95% CI, 1.11‐2.13). The frequency of severe bleeding complications did not differ. CONCLUSION: The results of the recent RCT are not inconsistent with those of the earlier studies. Introduction of PR technologies in their current stage of development would result in an increase in mild and moderate (albeit not severe) bleeding complications, which the transfusion‐medicine community must explicitly tolerate to reap the benefits from PR.     

Complications of extrapleural pneumonectomy

Extrapleural pneumonectomy (EPP) is a technically demanding operation that includes two body cavities within the operative field. Avoidance of postoperative deaths requires an experienced team that can identify common morbidities. The ability to recognize and intervene correctly in the early phases of postoperative complications can avoid deaths. Although our group has experienced only 20 deaths following 496 EPPs (4% mortality), there were 328 patients (66%) who suffered morbidity. We have drawn upon our single-institution experience to describe the most common source of morbidity following EPP and to offer successful interventions.     

Diabetes does not influence oral oncogenesis through fibroblast growth factor receptors

BACKGROUND: Increased expression of fibroblast growth factors and their receptors (FGFRs) has recently been described in oral squamous cell carcinoma. In addition, we have previously described a molecular basis for an association between oral cancer and diabetes. The expression of FGFR-2 and FGFR-3 investigated in an experimental model of chemically induced carcinogenesis in normal and diabetic (type I) rats. MATERIALS AND METHODS: Tissue sections ranging from normal mucosa to moderately-differentiated oral squamous cell carcinoma were studied using monoclonal antibodies against FGFR-2 and FGFR-3 proteins. RESULTS: A similar pattern of elevated FGFR-2 and FGFR-3 expression was observed in the initial stages of oncogenesis for both diabetic and non-diabetic animals. In the last stages of oral oncogenesis, the expression of both proteins remained relatively stable. CONCLUSION: It seems that diabetes does not affect the FGFR-2 and FGFR-3 pattern of expression throughout the various stages of oral oncogenesis.