High dose fractionated ionizing radiation inhibits prostate cancer cell adhesion and beta(1) integrin expression

BACKGROUND: The effect of ionizing radiation on extracellular matrix (ECM)-mediated cellular functions is an important area of research for translational science. Mechanisms of tumor cell ability to proliferate, migrate, and survive appear dependent on integrin-mediated adhesion to the ECM; however, the exact role therapeutic radiation plays in altering signaling pathways and promoting cell death within remains less well established. METHODS: To examine these effects on prostate carcinoma cell lines, cells were irradiated at sub-lethal doses. We have studied two human prostate cancer cell lines (PC3 and DU-145) irradiated with different fractionated radiation schedules. Three groups were compared to non-irradiated controls. Group A was given a single dose of 5 Gy. Group B was given 5 Gy the first week and then 10 Gy the second week for a total of 15 Gy. Group C was given 5 Gy the first week, and then 10 Gy the second and third week for a total of 25 Gy. Cells were analyzed at their prescribed total dose. At 48 hr post irradiation, cells were detached from culture dishes and were subsequently used for adhesion assays and immunoblotting analysis. RESULTS: Our findings revealed that two prostate carcinoma cell lines, PC3 and DU-145, had a reduced cellular adhesion to fibronectin (FN) compared to the non-irradiated control groups. Both prostate cancer cell lines showed decreased adhesion to FN and reduced beta(1) integrin protein levels at a total dose of 25 Gy, but not at the doses of 15 and 5 Gy. In a parallel analysis, at the maximum total dose of 25 Gy, both PC3 and DU-145 demonstrated a significant decrease in cell proliferation. CONCLUSIONS: High dose radiation treatment of prostate cancer cell lines inhibits integrin expression. Our study suggests that promoting a synergistic decrease in adhesion could bring additional therapeutic benefit to patients treated with radiation therapy.     

Assessment of health status in patients with cerebral palsy: what is the role of quality-of-life measures?

Measuring quality of life (QOL) in a population with a functional range as large as that of the pediatric cerebral palsy population is challenging. This study assessed the utility of two common QOL instruments in this population: the Child Health Questionnaire (CHQ) and the Pediatric Outcomes Data Collection Instrument (PODCI). The goal was to determine the efficacy of these questionnaires in detecting subtle differences in the QOL among children with cerebral palsy and to demonstrate the need for dynamic assessment when evaluating QOL within this group. There were 180 subjects between the ages of 5 and 18 years, split into three diagnostic groups-diplegic, hemiplegic, and quadriplegic. The PODCI was more sensitive to differences in the diplegic and hemiplegic groups, but quadriplegics exhibited a floor effect (50% or more scored at most 15 out of 100) in three of the five domains. The CHQ was more effective for the quadriplegic group, but the diplegic and hemiplegic diagnostic groups exhibited a ceiling effect on 2 of the 12 domains in that questionnaire. Because an instrument that uses dynamic assessment bases subsequent questions on the patient's response to the first ones, dynamic assessment would help to avoid ceiling and floor effects by asking questions more pertinent to the patient's actual condition, and it would save time that would have been wasted answering irrelevant questions about function and QOL.     

Delayed flexor digitorum superficialis and profundus ruptures in a trigger finger after a steroid injection: a case report

We report a case of delayed rupture of the flexor digitorum superficialis and profundus tendons after the use of local corticosteroid injections for trigger finger. The treatment involved the exploration, debridement, and placement of a silicone rod for planned flexor digitorum profundus staged reconstruction.     

Alternative to the modified jones procedure: outcomes of the flexor hallucis longus (FHL) tendon transfer procedure for correction of clawed hallux

BACKGROUND: The modified Jones procedure is the traditional operative procedure for correction of a clawed hallux, although the deformity may be caused by overpull of one of three different muscles. In this study we present the radiographic and functional outcomes of flexor hallucis longus (FHL) tendon transfer as treatment for clawed hallux. The transfer is performed by drawing two thirds of the FHL tendon up through a drill hole in the proximal phalanx and then suturing it medially back to the remaining third. METHODS: We retrospectively identified 19 patients (22 feet) who had FHL tendon transfer for correction of clawed hallux over a period of 5 years. Followup was an average of 51.0 (range 6 to 74; +/- 3.8) months after the procedure. Outcome and patient satisfaction were determined using the Long-Form Musculoskeletal Function Assessment (MFA) score. Patients were asked whether they were satisfied, somewhat satisfied, or dissatisfied with the overall outcome and were asked about shoewear limitations. Preoperative and postoperative radiographs were evaluated in 15 patients (17 feet). We measured the hallux valgus and interphalangeal (IP) angles on the anteroposterior (AP) radiographs. On the lateral view we measured the angle of the IP joint, the metatarsophalangeal (MTP) joint, and the talometatarsal angle. Statistical analysis was done using a repeated measures ANOVA (p < 0.05). RESULTS: On the lateral radiographs, the hallux IP joint angle (p < 0.0012; n = 15) and hallux MTP joint angle (p < 0.0265; n = 15) were significantly reduced postoperatively. On AP radiographs, the hallux valgus angle (p < 0.0334) was significantly reduced; however, the IP angle and the talometatarsal angle were not significantly different after surgery. Patients had an average MFA score of 14.6 (+/-3.8 standard error, range 1 to 35; n = 19). Thirteen patients were fully satisfied and six were somewhat satisfied with the overall result of the surgery. Four patients thought that their hallux limited the types of shoes they could wear, while 15 did not. CONCLUSION: It has been shown that clawed hallux can result from excessive motor function in one of three muscles: FHL tendon, peroneus longus (PL), and extensor hallucis longus (EHL). This study suggests that transfer of part of the tendon of the FHL is an effective alternative operative procedure for correction of clawed hallux.     

A spinal cord injured animal model of lower urinary tract function: observations using direct bladder and pelvic plexus stimulation with model microstimulators

BACKGROUND: Microstimulators are new devices that should be considered for management of lower urinary tract problems following spinal cord injury (SCI) such as urinary retention. These devices are small (less than 25 mm by 5 mm) with the electrodes located on the ends of the stimulator. However, it is not known whether the small electrodes on these devices would be effective in stimulating the plexus of nerves that innervate the bladder. The aim of the present study was to provide preliminary observations with model microstimulators (M-Micro) for inducing bladder contractions in an SCI animal model. Bladder wall and pelvic plexus stimulation sites were compared. Additional investigations evaluated parameters such as stimulation polarity, frequency, and period as well as bladder filling volume. METHODS: In an initial survival surgery, bilateral M-Micros were implanted on the bladder wall and the pelvic plexus along the urethra in 3 female cats. A second survival surgery was conducted 3 to 5 weeks later to produce a T1 0 SCI. Studies are reported following the second survival surgery. These studies included the effects of stimulation and bladder filling. RESULTS: The postmortem location of the implanted pelvic plexus M-Micro was previously described as near the bladder neck. Therefore, the pelvic plexus location is described in this report as "pelvic plexus (bladder neck)" stimulation. The observations showed effective stimulation with pelvic plexus (bladder neck) stimulation and voiding in some cases. Stimulation was limited by side effects of increased abdominal pressure and leg movement. Other factors also affected the response to stimulation, including the initial bladder volume and stimulating parameters. Fluoroscopy showed that when stimulation did not induce voiding the striated urethral sphincter was closed. CONCLUSIONS: This case series of 3 SCI animals showed that the small electrodes on the M-Micro could be used to stimulate the bladder with contractions and voiding in some cases. The pelvic plexus (bladder neck) location for the M-Micro may be a better location than higher on the bladder wall. Limiting side effects of stimulation included leg movement and increased abdominal pressure. Additional important factors included the stimulation parameters, initial bladder volume, and the function of the skeletal urethral sphincter.     

Spinal cord diffusion tensor imaging and fiber tracking can identify white matter tract disruption and glial scar orientation following lateral funiculotomy

Diffusion tensor magnetic resonance imaging (DTI) provides data concerning water diffusion in the spinal cord, from which white matter tracts may be inferred, and connectivity between spinal cord segments may be determined. We evaluated this potential application by imaging spinal cords from normal adult rats and rats that received cervical lateral funiculotomies, disrupting the rubrospinal tract (RST). Vitrogen and fibroblasts were transplanted into the surgical lesion at time of injury in order to fill the cavity. At 10 weeks, animals were sacrificed; the spinal cords were dissected out and then imaged in a 9.4-Tesla magnet. DTI tractography demonstrated the disruption of the rubrospinal tract axons while indicating which axon tracts were preserved. Additionally, DTI imaging could identify the orientation of glial processes in the gray matter adjacent to the site of injury. In the injured animals, reactive astrocytes in adjacent gray matter appeared to orient themselves perpendicular to white matter tracts. In summary, DTI identified not only white matter disruption following injury, but could distinguish the orientation of the accompanying glial scar.     

Cervical spine assessment in the unconscious trauma patient: a major trauma service's experience with passive flexion-extension radiography

BACKGROUND: There is no consensus on the most appropriate method of cervical spine assessment in unconscious trauma patients. Passive flexion-extension imaging is one option for further investigating unconscious patients whose plain cervical radiographs are normal. This study examines the usefulness of this passive imaging in investigating for occult cervical injury. METHODS: All unconscious patients admitted to The Alfred Trauma Intensive Care Unit over 1 year (January 1-December 31, 1998), who could not be clinically assessed within 48 hours in regard to their cervical spine, were identified. Results of passive flexion-extension radiography were compared with final injury status and clinical outcome as determined by retrospective review of the imaging reports, radiographic films, and case notes. RESULTS: One hundred twenty-three patients with normal three-view plain radiographs proceeded to passive functional investigation. These were false-negative in four of the seven patients with cervical spine injuries at presentation. No patients suffered any adverse neurologic events from their delayed diagnoses or from the flexion-extension procedure. CONCLUSION: Passive flexion-extension imaging has inadequate sensitivity for detecting occult cervical spine injuries. Although no patients suffered adverse neurologic complications, the potential for devastating consequences from missed cervical injury has resulted in the removal of passive flexion-extension imaging from the screening protocol.     

Gender differences in 24-hour urinary diaries of asymptomatic North American adults

PURPOSE: Two previously published studies from our center have described the urinary habits of asymptomatic men (284) and women (300) as revealed by 24-hour urinary diaries. Those gender specific studies found that urinary diary variables are affected by age and race. By comparing the data from those studies we determined the effect of gender on voiding habits. MATERIALS AND METHODS: In this secondary analysis we matched each female urinary diary to that of a male of similar age and race. Diary variables were compared using paired sign tests with results considered significant at the 5% level. RESULTS: A total of 141 matched pairs were studied. The population age ranged from 18 to 68 years and was racially diverse (56% black, 31% white, 7% Hispanic and 6% Asian). Men had higher total fluid intake and mean voided volume than women (p <0.001 and 0.04, respectively). Women voided more frequently than men (p = 0.006) and had more voids per liter of fluid intake (p <0.001). No gender differences were found for body mass index, nighttime or daytime diuresis rates, total urine volume, maximum voided volume or rates of nocturia. CONCLUSIONS: This analysis suggests that there are significant gender effects on 24-hour diary variables, with females tending to void more often and at lower mean volumes. The results of our study may be useful in the design of research studies or for patient counseling.     

Amino acids injure mesangial cells by advanced glycation end products, oxidative stress, and protein kinase C

BACKGROUND: In diabetes, high intake of dietary protein exacerbates responses associated with kidney damage. Increased levels of amino acids could injure cells by providing free amino groups for glycation reactions leading to advanced glycation end products (AGEs). METHODS: Rat mesangial cells were cultured with increased amino acids designed to resemble protein feeding, high glucose (30.5 mmol/L), and, the combination, amino acids/high glucose. AGEs, reactive oxygen species (ROS), protein kinase C (PKC) activity and production, and mitogen-activated protein (MAP) kinase-extracellular signal regulated kinase (ERK) 1,2 activity were measured. Inhibitors were used to determine roles of these processes in fibrosis and/or AGE formation. RESULTS: AGE immunostaining increased when cells were cultured in amino acids and was comparable to that observed with high glucose. In amino acids/high glucose, AGE immunostaining appeared even greater. Amino acids, high glucose, and amino acids/high glucose induced ROS production. Aminoguanidine and vitamin E prevented AGE accumulation and induction of protein and mRNA for fibrosis markers [transforming growth factor-beta1 (TGF-beta1), fibronectin, and collagen IV]. PKC and ERK 1,2 activity increased with amino acids, high glucose, and amino acids/high glucose. PKC-beta inhibition prevented ERK 1,2 activation and fibrosis induction. ERK 1,2 inhibition also blocked the fibrosis response. CONCLUSION: A profibrotic injury response occurred in mesangial cells exposed to amino acids, with or without high glucose, by formation of AGE, oxidative stress, and activation of the PKC-beta and MAP kinase-ERK 1,2 signal pathway. These observations provide new insight into cellular mechanisms of kidney damage produced by excess dietary protein, particularly in diabetes.