Phase I trial of BCL-2 antisense oligonucleotide (G3139) administered by continuous intravenous infusion in patients with advanced cancer.

PURPOSE: To evaluate the safety and pharmacokinetics of BCL-2 antisense oligonucleotide (G3139) administered by prolonged i.v. infusion in patients with advanced cancer. EXPERIMENTAL DESIGN: A total of 35 patients was treated in cohorts of 3-6 with 0.6-6.9 mg/kg/day of BCL-2 antisense oligonucleotide as a continuous infusion for 14 or 21 days. Plasma levels of intact antisense oligonucleotide were measured in all patients. RESULTS: G3139 was generally well tolerated. At the highest dose level examined in this study (6.9 mg/kg/day), fatigue and transient reversible elevations of serum transaminases (grades 2-3) became apparent after >or=7 days of treatment. Both reactions were believed to be drug related. Pharmacokinetic analyses showed that steady-state plasma concentrations of G3139 were reached approximately 10 h after starting the infusion and increased linearly across the range of doses administered 相似文献   

Prevalence of antibodies to Toxoplasma gondii in the female population of the County of Split Dalmatia, Croatia

The prevalence of IgG antibodies reactive with Toxoplasma gondii in the female population of the County of Split Dalmatia was investigated by enzyme linked immunosorbent assay. Of a total of 1109 serum samples collected from female subjects, 423 (38.1%) reacted with T. gondii. The frequency of positive sera increased with age. Theoretical incidence of congenital toxoplasmosis was calculated from the annual increase in cumulative prevalence of antibodies between different age groups among the women of childbearing age. The estimated theoretical incidence of congenital toxoplasmosis was 1.4 per 100 pregnancies of adolescents (16–20 years) and decreased to 0.1% in seronegative pregnant women aged 41–45.     

Association of disease progression and poor overall survival with detection of circulating tumor cells in peripheral blood of patients with metastatic breast cancer

The aim of this study was to define the frequency and clinical relevance of cytokeratin positive metastatic tumor cells in the peripheral circulation of patients with stage IV breast cancer. Peripheral blood was collected from 32 consecutive patients with metastatic breast cancer and 23 healthy donors. Tumor cells were enriched using positive selection with anti-HEA125-microbeads and cytospins were prepared of the positive selection eluate. Slides were incubated with a Fab2 fragment of the pancytokeratin antibody A45-B/B3 conjugated with alkaline phosphatase (AKP) and a CAM5.2-AKP monoclonal antibody and developed with an alkaline phosphatase anti-alkaline phosphate reaction (APAAP). All samples were evaluated using light microscopy and an automated image analysis system. In 8/32 (25%) patients cytokeratin positive (CK+) cells could be detected after anti-HEA125 enrichment in the peripheral blood whereas in none out of 23 healthy donors. One to 1000 (median 5) positive cells per patient sample were observed and cluster of tumor cells in one patient. Automated image analysis was as powerful in detecting micrometastases as conventional light microscopy. All patients with CK+ cells in the peripheral circulation (8/8, 100%) showed progressive disease at the time-point of blood draw whilst only 9/24 (37.5%) showed disease progression without detection of positive cells. The median overall survival of CK+ patients was 4+/-2 months compared to 13+/-7 months of CK- patients (p<0.001). CK+ cells are detectable in the peripheral circulation of 25% of patients with metastatic breast cancer after positive selection with anti-HEA125. Detection of tumor cells in the peripheral circulation might be correlated with progression of disease and shorter overall survival.     

Multiple primary intrathoracic neoplasms: case report and a review of the literature

This is a case report of a patient diagnosed with three distinct primary intrathoracic tumors (mesothelioma, carcinoid and B-cell lymphoma). The patient had previously had mycosis fungoides. The occurrence of multiple neoplasms in a single patient, synchronous or metasynchronous, is not a rare phenomenon; the incidence varies from 1-11% of all neoplasms. They can be hereditary, or connected with some environmental agents or previous therapies. The incidence of multiple neoplasms increases with age. We report an extremely rare case of multiple intrathoracic neoplasms in a 71-year-old man. A left upper lobectomy was performed, followed by 6 courses of chemotherapy and irradiation of the sternum. The patient was stable two years later.     

Moxifloxacin in experimental Streptococcus pneumoniae cerebritis and meningitis

Rifampin, a protein synthesis inhibitor, reduced mortality in a mouse model of meningitis compared to bacteriolytic cephalosporin standard therapy. To assess whether moxifloxacin (known to cause a less rapid bacteriolysis than cephalosporins) can similarly reduce mortality, mice infected with Streptococcus pneumoniae by deep intracerebral injection were treated subcutaneously with either 200 mg/kg of moxifloxacin or ceftriaxone every 8 hours for 5 days (n=49 each). They were then observed for an additional 8 days. Overall mortalities were 35 and 29 in moxifloxacin- and ceftriaxone-treated mice, respectively (p=0.29). Kaplan-Meier survival analysis also revealed no statistically significant differences (p=0.32). Moxifloxacin failed to reduce mortality compared to cephalosporin standard therapy.     

Superoxide dismutase activity in colostrum, transitional and mature human milk

Colostrum and mature human milk are rich sources of nutrients and contain biologically active molecules that are essential for specific antioxidant functions. The aim of the present study was to determine the activity of copper, zinc superoxide dismutase (CuZnSOD) and manganese superoxide dismutase (MnSOD) activity in different phases of lactation. Specific enzyme activity was determined in colostral milk (3rd-5th days after delivery), and in mature milk in the third week (15-20 days), and the fourth and seventh months of lactation. In the third week of lactation, the activity of CuZnSOD and MnSOD was significantly higher in comparison to the colostral phase. In the fourth month of lactation, the activity of both enzymes was suppressed, while in the seventh month of lactation the MnSOD activity was increased, and the CuZnSOD activity was not significantly changed. These findings show that the activities of superoxide dismutases significantly change during different phases of lactation.     

Psychodermatology: a brief review for clinicians

Psychodermatologic disorders are conditions involving an interaction between the mind and the skin. These disorders fall into three major categories: psychosomatic disorders, primary psychiatric disorders and secondary psychiatric disorders (Koo 1995). The treatment of psychodermatologic disorders is almost impossible without a holistic team approach involving psychiatrist, dermatologist and psychologist. Majority of psychodermatologic disorders can be treated with cognitive-bihevioral psychotherapy, psychoterapeutic stress-and-anxiety-management techniques and psychotropic drugs. Psychopharmacologic treatment with anxiolytics, antidepressants, antipsychotics and mood stabilizers can be prescribed by dermatologist, after consulting the psychiatrist.