Tumor necrosis factor alpha-induced endothelial tissue factor is located on the cell surface rather than in the subendothelial matrix

Because there is no consensus regarding the precise distribution of induced endothelial tissue factor (TF), we studied TF activity in and on tumor necrosis factor alpha-stimulated cultured human umbilical vein endothelial cells (ECs) and their underlying matrix. TF was mainly expressed on the cell surface. Only small traces were found on the apical surface suggesting that TF is predominantly located on the basolateral side of the cell membrane. The presence of TF on the cell surface was confirmed by flow cytometry. Subendothelial TF activity appeared to be dependent upon the procedure used to remove the stimulated EC monolayer. Whereas ammonium hydroxide or hypotonic lysis resulted in relatively high levels of matrix-associated TF, virtually no TF was found on the matrix after mild enzymatic detachment of stimulated ECs. Cell removal with EDTA resulted in intermediate levels of matrix-associated TF. Neither the enzymatic treatment nor EDTA degraded or removed this TF activity. Similar patterns were observed for matrix-associated TF antigen and EC surface markers. Electron microscopic analysis showed cell fragments on the matrix after monolayer lysis. The findings strongly suggest that induced endothelial TF associated with the subendothelial matrix actually represents TF on EC remnants.     

An evaluation of interventions designed to stimulate physician reporting of adverse drug events

A frequent complaint among health care professionals about ADE reporting programs is that they never know what happens to the information they took the time and effort to report. In the Mississippi ADE program, physicians appreciated the feedback they were provided--in letter form--indicating the ultimate disposition of the reported information. Also, a regular newsletter summarizing the number and types of reports and the drugs involved was well received. This vehicle was also used to educate physicians about new drugs on the market that warranted closer scrutiny. Reminder posters placed at strategic points around the hospital and periodic inservices on the program are effective in maintaining a level of awareness about the importance of ADE monitoring and its impact on the quality of care.     

Alprazolam and diazepam: addiction potential

Alprazolam and diazepam, the two most prescribed benzodiazepine anxiolytics in the United States, have potential for addictive use. The Drug Abuse Warning Network (DAWN) indicates they are the most mentioned benzodiazepines, and the National Household Survey indicates significant abuse of tranquilizers. Both drugs are rapidly absorbed and enter the brain tissue rapidly, leading to reinforcement. Alprazolam has a shorter half-life, which may lead to more withdrawal symptoms than diazepam. In experimental conditions, they are among the most reinforcing benzodiazepines. Each causes a withdrawal syndrome, but alprazolam withdrawal may be more severe and may occur after a shorter period of use. Adverse effects from their use are said to be rare, yet subtle negative consequences may be seen with some regularity. Alprazolam deserves special caution because of its relative newness, great popularity, reinforcing capabilities, relatively severe withdrawal syndrome, and reports of addiction and negative consequences of use.     

Ewing's sarcoma family of tumors: current management

Ewing's sarcoma is the second most frequent primary bone cancer, with approximately 225 new cases diagnosed each year in patients less than 20 years of age in North America. It is one of the pediatric small round blue cell tumors, characterized by strong membrane expression of CD99 in a chain-mail pattern and negativity for lymphoid (CD45), rhabdomyosarcoma (myogenin, desmin, actin) and neuroblastoma (neurofilament protein) markers. Pathognomonic translocations involving the ews gene on chromosome 22 and an ets-type gene, most commonly the fli1 gene on chromosome 11, are implicated in the great majority of cases. Clinical presentation is usually dominated by local bone pain and a mass. Imaging reveals a technetium pyrophosphate avid lesion that, on plain radiograph, is destructive, diaphyseal and classically causes layered periosteal calcification. Magnetic resonance best defines the extent of the lesion. Biopsy should be undertaken by an experienced orthopedic oncologist. Approximately three quarters of patients have initially localized disease. About two thirds survive disease-free. Management, preferably at a specialist center with a multi-disciplinary team, includes both local control-either surgery, radiation or a combination-and systemic chemotherapy. Chemotherapy includes cyclic combinations, incorporating vincristine, doxorubicin, cyclophosphamide, etoposide, ifosfamide and occasionally actinomycin D. Topotecan in combination with cyclophosphamide has shown preliminary activity. Patients with initially metastatic disease fare less well, with about one quarter surviving. Studies incorporating intensive therapy followed by stem cell infusion show no clear benefit. New approaches include anti-angiogenic therapy, particularly since vascular endothelial growth factor is an apparent downstream target of the ews-fli1 oncogene.