Cataract surgery and diabetic retinopathy

Diabetes is a risk factor for the development of cataracts. Studies have shown an increased risk of ocular complications in diabetics after cataract surgery, but modern surgical techniques have minimized them, leading to an overall good visual outcome. Macular edema before surgery is the most common condition that limits post-operative visual recovery. Thus, pre-operative laser treatment is needed. Photocoagulation of preproliferative or early proliferative diabetic retinopathy is also advisable, due to the increased risk of iris neovascularization or retinopathy progression after surgery.     

Proton pump inhibitor treatment of patients with gastroesophageal reflux-related chronic cough： A comparison between two different daily doses of lansoprazole

AIM:To compare two different daily doses oflansoprazole given for 12 weeks and to assess the roleof gastrointestinal (GI) investigations as criteria forselecting patients.METHODS:Out of 45 patients referred for unexplainedchronic persistent cough,36 had at least one of theGI investigations (endoscopy,24-h esophageal pH-metry and a 4-week trial of proton pump inhibitor (PPI)therapy) positive and were randomly assigned to receiveeither 30 mg lansoprazole o.d.or 30 mg lansoprazoleb.i.d,for 12 weeks.Symptoms were evaluated atbaseline (visit 1) after the PPI test (visit 2) and after the12-week lansoprazole treatment period (visit 3).RESULTS:Thirty-five patients completed the studyprotocol.Twenty-one patients (60.0%) reportedcomplete relief from their cough with no differencebetween the two treatment groups (58.8% and 61.1%had no cough in 30 mg lansoprazole and 60 mglansoprazole groups,respectively).More than 80% ofthe patients who had complete relief from their cough atthe end of the treatment showed a positive response tothe PPI test.CONCLUSION:Twelve weeks of lansoprazole treatmenteven at a standard daily dose,is effective in patientswith chronic persistent cough.A positive response to aninitial PPI test seems to be the best criterion for selectingpatients who respond to therapy.     

Clinical experience with gefitinib: an update

Gefitinib is an orally active, selective epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) that blocks signal transduction pathways involved in cell proliferation. This drug demonstrated impressive and durable responses in patients with heavily pretreated non-small cell lung cancer (NSCLC). In two large phase II trials, responses were observed in 9-19% of unselected patients, along with symptom improvement and benefit in quality of life. Biological mechanisms underlying TKI sensitivity have recently been discovered. There is evidence that specific EGFR gene mutations and/or amplification confer a particularly sensitive phenotype, especially in individuals with tumors demonstrating activation of the anti-apoptotic protein Akt. However, in all so far conducted clinical trials, no patient selection has been made, providing a logical explanation for the negative results observed in large phase III studies. In the present review, we will summarize the results observed in clinical trials with gefitinib. We will present results obtained in NSCLC and in other solid tumor, focusing on biological and clinical markers predicting drug sensitivity.     

Actin polymerization in neutrophils from donors of peripheral blood stem cells: divergent effects of glycosylated and nonglycosylated recombinant human granulocyte colony-stimulating factor

Neutrophil functions can be modified by Recombinant human G-CSF (rhG-CSF) treatment, with divergent effects on phagocytosis, motility, bactericidal activity, and surface molecule expression. Neutrophil morphology is modified by treatment with filgrastim (the nonglycosylated form of rhG-CSF), while it is not affected by lenograstim (the glycosylated type of rhG-CSF). Little information is available about actin polymerization in neutrophils from subjects treated with the two types of rhG-CSF. In the current paper we evaluated two groups of donors of peripheral blood stem cells (PBSC) for allogeneic transplantation. Ten subjects were treated with filgrastim and 10 with lenograstim to mobilize PBSC; 15 blood donors were evaluated as a control group. Actin polymerization (both spontaneous and fMLP-stimulated) was studied by a flow cytometric assay. A microscopic fluorescent assay was also carried out to evaluate F-actin distribution in neutrophils. We found that filgrastim induced an increased F-actin content in resting neutrophils, along with morphologic evidence for increased actin polymerization distributed principally at the cell membrane and frequently polarized in focal areas; in addition, fMLP was not able to induce further actin polymerization. On the contrary, treatment with lenograstim was associated with F-actin content, distribution, and polymerization kinetics indistinguishable from those displayed by control neutrophils. Such experimental results show that filgrastim and lenograstim display divergent effects also on neutrophil actin polymerization and provide further explanation for previous experimental findings.     

Giant congenital aortic aneurysm with cleft sternum in a neonate: pathological and surgical considerations for optimal management

We report a rare case of a neonate with congenital giant aortic aneurysm associated to cleft sternum, who underwent surgical repair. The patient died on postoperative Day 5 from cardiac arrest. Autopsy revealed a circumferential subendocardial myocardial infarction and misdiagnosed coronary ostial anomalies. A critical analysis of this unfortunate case may help optimal surgical planning in similar patients in the future.     

Mutant p53 proteins: between loss and gain of function

Cancer might result from both the aberrant activation of genes, whose physiological tuning is essential for the life of a normal cell, and the inactivation of tumor suppressor genes, whose main job is to preserve the integrity of cell genome. Among the latter, p53 is considered a key tumor suppressor gene that is inactivated mainly by missense mutations in half of human cancers. It is becoming increasingly clear that the resulting mutant p53 proteins gain oncogenic properties favoring the insurgence, the maintenance, and the spreading of malignant tumors. In this review, we mainly discuss the molecular mechanisms underlying gain of function of human tumor-derived p53 mutants, their impact on the chemoresistance and the prognosis of human tumors, with a special focus on head and neck cancers, and the perspectives of treating tumors through the manipulation of mutant p53 proteins.     

Silica-based mesoporous materials as drug delivery system for methotrexate release

Antineoplastic methotrexate has been loaded through different soaking procedures on silica-based mesoporous materials and, successively, released mimicking an oral administration. The materials were prepared using a self-assembly mechanism in the presence of cationic surfactants with alkyl chain of 16, 12, and 10 carbon atoms in the synthesis mixture to obtain different pore diameter in the porous structure. Mesoporous materials were prepared as pure silica sample and in the presence of Al(OH)₃ in the synthesis mixture. Only alumina-silica samples were able to load methotrexate. The amounts of drug loaded and the in vitro release kinetics are a function of the pore size of the materials.