Medium-mediated intercellular communication is involved in bystander responses of X-ray-irradiated normal human fibroblasts

Although radiation-induced bystander effects have been demonstrated in a number of cell types, the studies have largely been performed using high linear energy transfer (LET) radiation, such as alpha-particles. The literature is contradictory on whether fibroblasts show bystander responses, especially after low LET radiation such as X- or gamma-rays and whether the same signal transmission pathways are involved. Herein, a novel transwell insert culture dish method is used to show that X-irradiation induces medium-mediated bystander effects in AGO1522 normal human fibroblasts. The frequency of micronuclei formation in unirradiated bystander cells increases from a background of about 6.5% to about 9-13% at all doses from 0.1 to 10 Gy to the irradiated cells. Induction of p21Waf1 protein and foci of gamma-H2AX in bystander cells is also independent of dose to the irradiated cells above 0.1 Gy. In addition, levels of reactive oxygen species (ROS) were increased persistently in directly irradiated cells up to 60 h after irradiation and in bystander cells for 30 h. Adding Cu-Zn superoxide dismutase (SOD) and catalase to the medium decreases the formation of micronuclei and induction of p21Waf1 and gamma-H2AX foci in bystander cells, suggesting oxidative metabolism plays a role in the signaling pathways in bystander cells. The results of clonogenic assay of bystander cells showed that survival of bystander cells decreases from 0 to 0.5 Gy, and then is independent of the dose to irradiated cells from 0.5 to 10 Gy. Unlike the response with p21Waf1 expression, gamma-H2AX foci and micronuclei, adding SOD and catalase has no effect on the survival of bystander cells. The data suggest that irradiated cells release toxic factors other than ROS into the medium.     

A prognostic index (bladder prognostic index) for bilharzial-related invasive bladder cancer

PURPOSE: Bladder cancer is still the most common solid tumor among adult males in Egypt because of the prevalence of bilharzial infestation, especially in the countryside. In this prospective study, we have recorded the prognostic factors for 180 patients with invasive bladder cancer for whom standard radical cystectomy had been performed to develop a prognostic index (bladder prognostic index) that defines high risk patients who are more vulnerable to disease relapse after surgery and who may benefit from additional therapy. PATIENTS AND METHODS: The study was performed between January 1997 and December 1999, in which 180 patients with histopathologically proved invasive bladder cancer associated with bilharziasis underwent radical cystectomy or anterior pelvic exenteration. After surgery, patients were regularly followed for a minimum of 2 years. RESULTS: Our patients included 141 males and 39 females. Squamous cell carcinoma was the most common type (53.3%), and most of the tumors were grade II (61.1%). A total of 173 patients had their tumors operable, while 7 were inoperable. We had 5 (2.8%) operative related mortalities. At 5 years postoperatively, free and overall survival rates for the whole group of patients were 31.44%+/-5.9% and 32.5%+/-6.8%, respectively. Tumor pathologic stage, grade, and nodal affection were the only significant factors with impact on survival (P=0.008, 0.051, and 0.004, respectively). These 3 prognostic indexes were used to design a model to predict an individual patient's risk factor for recurrence. Patients were then assigned to one of the 4 risk groups according to the score achieved in this prognostic index (0=low risk, 1=intermediate risk, and 2 or 3=higher risk). These 4 risk groups had distinctly different rates of disease-free survival, i.e., 91.7%, 53%, 13%, and 7% for low, intermediate, and higher risk groups, respectively. CONCLUSION: Although this prognostic index appears to be of a significant clinical relevance, it needs to be more validated on a larger number of patients, and it could be a surrogate variable for biologic factors responsible for the heterogeneity of bladder cancer.     

CT pulmonary angiography: a comparative analysis of the utilization patterns in emergency department and hospitalized patients between 1998 and 2003

OBJECTIVE: The purpose of our study was to objectively examine the temporal utilization patterns of CT pulmonary angiography in emergency department and hospitalized patients in an academic tertiary care center. SUBJECTS AND METHODS: Patients who underwent CT examination for suspected pulmonary embolism either through our emergency department or as inpatients during a recent 9-month interval were identified. The absolute number of studies and incidence of positive results and ancillary findings were compared with similar data published from our institution during the corresponding 9-month interval in 1997-1998. RESULTS: The overall number of patients imaged for pulmonary embolism was significantly greater in the 2002-2003 period than in the 1997-1998 period (homogeneity of rates = 88.45, p < 0.0001). The absolute number of scans obtained was significantly greater in both the emergency department (chi(2) = 167.03, p < 0.0001) and inpatient (chi(2) = 210.62, p < 0.0001) groups in the more recent population. Significantly fewer ancillary findings were reported in both the emergency department (chi(2) = 5.93, p = 0.019) and inpatient (chi(2) = 6.03, p = 0.015) groups in the more recent population. The incidence of CT-detected pulmonary embolism was significantly less in both the emergency department (chi(2) = 34.26, p < 0.0001) and inpatient (chi(2) = 8.52, p < 0.01) groups in the more recent population. This decrease in the incidence of scans with positive findings for pulmonary embolism over time was significantly greater in the emergency department group than the inpatient group (homogeneity of odds = 0.003, p < 0.007). CONCLUSION: The evolution of CT pulmonary angiography utilization has led to a significant increase in the number of patients being imaged for pulmonary embolism with a coincident significant decrease in the rates of CT-detected pulmonary embolism and ancillary findings both in emergency department and hospitalized patients.     

The corporo-glans ligament: description and functional significance of a ligament connecting the corpora cavernosa to the glans penis

The two corpora cavernosa (CC) end blindly under cover of the glans penis (GP). The method of attachment of the CC to the GP could not be traced in the literature. The current communication investigated the hypothesis of a ligamentous attachment existing between the two corporal ends and the GP. In all, 18 male cadaveric specimens were studied by direct dissection and histologically. Six were neonates and 12 adults (mean age 32.3+/-10.6 s.d. y). After examining and photographing the connection between the CC and GP, sagittal, parasagittal, and coronal sections of the connection were stained and studied microscopically. A triangular fibrous tissue band connected the distal blind ends of the two CC with the GP. The base of this band was attached to the tunica albuginea of the two CC, while the apex was continuous with the fibrous septa between the sinusoids of the cavernous tissue of the GP. Microscopically, the ligament consisted of collagen and elastic fibers; in some sections, the collagen fibers of the tunica albuginea were continuous with those of the band. A band of collagen and elastic fibers could be identified connecting the two CC to the GP; we term it the 'corporo-glans ligament'. This ligament presumably affords the connection with rigidity, flexibility, and tissue strength. We suggest that it firmly connects the GP to the CC during penile thrusting. Further studies are required to assess the possible role of this ligament in erectile dysfunction.