An experimental model of the production of early after depolarizations by injury current from an ischemic region

An ischemic myocardial region contains cells with a depolarized resting membrane potential. This depolarization leads to an intercellular current flow between the ischemic region and the surrounding normal myocardial cells which has been termed an injury current. We have devised an experimental model system in which an isolated guinea pig ventricular cell is electrically coupled to a model depolarized cell in order to evaluate the effects of this injury current on the electrical properties of a normal ventricular cell exposed to drugs which increase calcium current or decrease potassium current. Using low doses of isoproterenol, forskolin, or Bay K 8644 (or 8-bromo-cyclic adenosine monophosphate in the pipette) we found that the action potential duration of the isolated cell was lengthened, but that early after depolarizations (EADs) were not produced unless the cell was also coupled to a depolarized cell model representing an adjacent ischemic region. A similar prolongation of the action potential was produced by low doses of quinidine, but EADs were not produced unless coupling to a depolarized cell model was added. EADs could not be produced in any cells in the absence of the drugs even though the coupling to the depolarized cell model was increased up to the level at which the action potential was indefinitely prolonged. At higher isoproterenol concentrations, EADs or spontaneous activity were produced without coupling to the depolarized cell model. Under these conditions, coupling of the cell to a cell model with normal resting membrane potential stopped the spontaneous activity and prevented the occurrence of EADs even with high levels of resistive coupling. These findings suggest that the electrotonic influences of a localized depolarized region can produce EADs if the calcium current magnitude is increased, which would be the case for sympathetic innervation.     

Assessing the perceived importance of skin cancer: how question-order effects are influenced by issue involvement.

Question-order effects refer to systematic differences in responses that can be attributed to the manner in which questions assessing attitudes and cognitions are asked. This article hypothesized that question-order effects in assessing the perceived importance of skin cancer would be moderated by the extent to which people are involved with the issue of skin cancer. A telephone survey (N=325) was conducted by administering two versions of the same questionnaire, one in which importance of skin cancer was assessed without other contextual variables and another in which contextual variables were asked before assessing the importance of skin cancer. As hypothesized, when people were highly involved with the issue, question-order effects did not occur. When involvement was low, importance of skin cancer was greater in the absence of contextual questions than in their presence. Findings have implications for how health-related issues are communicated to the public and how formative research is conducted.     

Flat-panel volume computed tomography for cochlear implant electrode array examination in isolated temporal bone specimens.

HYPOTHESIS: Flat-panel based volume computed tomography could improve cochlear implant electrode evaluation in comparison with multislice computed tomography. BACKGROUND: Flat-panel based volume computed tomography offers higher spatial resolution and less metal artifacts than multislice computed tomography. Both characteristics could improve the evaluation of challenging but important questions in cochlear implantation assessment, such as an exact imaging of cochlea, osseous spiral lamina, electrode array position, and single electrode contacts. These questions are not currently fully answered by multislice computed tomography. METHODS: Four isolated temporal bone specimens were scanned in a current multislice computed tomography scanner and in two experimental flat-panel based volume computed tomography scanners before and after cochlea implantation. To compare flat-panel based volume computed tomography and multislice computed tomography, four features were rated according to the following criteria: 1) visibility of the cochlea; 2) visibility of the osseous spiral lamina; 3) discernibility of individual electrode contacts; and 4) the ability to determine the electrode array position relative to scala tympani and scala vestibuli. Layer-by-layer microgrinding pictures were used as the ground truth for verification of imaging findings. RESULTS: Flat-panel based volume computed tomography was superior to multislice computed tomography in all four features rated. The cochlea and facial nerve canal were much better delineated in flat-panel based volume computed tomography. The osseous spiral lamina and single electrode contacts were only visible in flat-panel based volume computed tomography. Assessment of implant position with regard to the cochlear spaces was considerably improved by flat-panel based volume computed tomography. CONCLUSION: Cochlear implantation assessment could be improved by flat-panel based volume computed tomography and, therefore, would be highly beneficial for cochlea implantation research and for clinical evaluation. However, these first results were shown by scanning isolated temporal bone specimens; scanning whole human skull bases might be more challenging.     

High precision conformal radiotherapy employing conservative margins in childhood benign and low-grade brain tumours.

BACKGROUND AND PURPOSE: To report local control and follow up outcome data of high precision conformal radiotherapy in childhood brain tumours. MATERIALS AND METHODS: Between December 1999 and December 2002, 26 children (17 boys and 9 girls, median age 11.5 years) with incompletely excised or recurrent benign and low-grade brain tumours [13 craniopharyngiomas, 11 low-grade gliomas (LGG) and 2 others] were treated with three-dimensional (3D) conformal radiotherapy (CRT) (12 patients) and stereotactic conformal radiotherapy (SCRT) (14 patients). Gross tumour volume (GTV) included neuro-imaging based visible tumour and/or resected tumour bed. Clinical target volume (CTV) consisted of GTV+ 5 mm margin and planning target volume (PTV) consisted of additional 5 mm margin for CRT and 2 mm for SCRT. Treatment was delivered with 3-9 conformal fixed fields to a median dose of 54 Gy/30 fractions. RESULTS: The actuarial 2 and 3 year disease free and overall survival was 96 and 100%, respectively (median follow up: 25 months, range 12-47 months). Radiological follow up available in 25 patients revealed complete response in 1, partial regression in 10, stable disease in 13 and progression in 1 patient (within the CTV). One patient with craniopharyngioma on a routine imaging revealed a mild asymptomatic cyst enlargement, which resolved with conservative management. A patient with chiasmatic glioma developed cystic degeneration and hydrocephalus 9 months after SCRT requiring cyst drainage and placement of a ventriculoperitoneal shunt. CONCLUSION: High-precision conformal techniques delivering irradiation to a computer generated target volume employing 7-10 mm 3D margins beyond the visible tumour and/or resected tumour bed appear to be safe in children with incompletely resected or recurrent benign and low-grade brain tumours, based on these data.     

CT cisternography in cerebrospinal fluid rhinorrhea: Could it have a therapeutic role?

Two cases of spontaneous cessation of cerebrospinal fluid (CSF) rhinorrhea following iohexol computerized tomographic (CT) cisternography are presented. This report contradicts the current thinking about conservative treatment in CSF rhinorrhea. We propose that iohexol CT cisternography may have a therapeutic role in the management of spontaneous CSF rhinorrhea.     

Primary vaginal cancer treated with concurrent chemoradiation using Cis-platinum

PURPOSE: To evaluate the feasibility of concurrent weekly Cis-platinum chemoradiation (CRT) in the curative treatment of primary vaginal cancer. METHODS: A retrospective review was performed of all primary vaginal cancer patients treated with curative intent at the Ottawa Hospital Regional Cancer Centre between 1999 and 2004 using concurrent Cis-platinum CRT. RESULTS: Twelve patients were treated with concurrent weekly CRT. The median age at diagnosis was 56 years (range, 34-69 years), and the median follow-up was 50 months (range, 11-75 months). Ten patients (83%) were diagnosed with squamous cell carcinoma and 2 patients (17%) with adenocarcinoma. The distribution according to stage was as follows: 6 (50%) Stage II, 4 (33%) Stage III, and 2 (17%) Stage IVA. All patients received pelvic external beam radiotherapy (EBRT) concurrently with weekly intravenous Cis-platinum chemotherapy (40 mg/m(2)) followed by brachytherapy (BT). The median dose of EBRT was 4500 cGy given in 25 fractions over 5 weeks. Ten patients received interstitial BT, and 2 patients received intracavitary BT, with the median dose being 3000 cGy. The 5-year overall survival, progression-free survival, and locoregional progression-free survival rates were 66%, 75%, and 92%, respectively. Late toxicity requiring surgery occurred in 2 patients (17%). CONCLUSIONS: For the treatment of primary vaginal cancer, it is feasible to deliver concurrent weekly Cis-platinum chemotherapy with high-dose radiation, leading to excellent local control and an acceptable toxicity profile.     

Antioxidant gene expression in preeclamptic placentae: a preliminary investigation

Oxidative stress has been implicated in the pathogenesis of preeclampsia. This study measured the relative mRNA expression of antioxidant proteins glutathione peroxidase 1 and 4, glutathione reductase, thioredoxin 1 and 2, thioredoxin reductase 1, thioredoxin peroxidase 3 and superoxide dismutase 1 and 2 in preeclamptic and non-preeclamptic placentae. Quantitative real-time PCR was conducted on placental mRNA isolated from preeclamptic and control patients. Cycle threshold numbers and fold differences were calculated as a measure of linear product amplification and used for comparison. The mRNA expression of glutathione reductase was significantly reduced (fold difference 0.41, p<0.05) in preeclamptic placenta when compared to controls while the expression of thioredoxin peroxidase 3 was significantly increased (fold difference 3.25, p<0.001) in the preeclamptic placentae. No significant difference in expression was observed for glutathione peroxidase 1 and 4, thioredoxin 1 and 2, thioredoxin reductase 1 and superoxide dismutase 1 and 2. These results suggest that it is the abnormal oxidative insult associated with preeclampsia not mRNA expression of antioxidant proteins that may be responsible for reduced antioxidant enzyme activity in preeclamptic placentae.     

Chronic inflammatory demyelinating polyneuropathy: A unique case of chronic disease with atypical features

We present a unique case of diffusely extensive Chronic Inflammatory Demyelinating Polyneuropathy (CIDP). Typically affecting the peripheral nervous system and manifesting with muscle weakness, breakdown or paresthesia, we present a case that additionally demonstrates; cranial nerve involvement, central nervous system parenchymal lesions, and chronic osseous remodeling of the nerve tracts. Cranial nerve involvement to this extent has only been described in one other case report to our knowledge. Central nervous system parenchymal lesions are extremely rare in CIDP and no discrete discussion about osseous remodeling has been presented, thus far, in the literature. The findings illustrated in this case may spur further understanding of imaging characteristics most associated with chronic CIDP disease and care measures that could help stratify patients most at risk for severe symptomologies.     

Treatment of Bone Tumors

In this article, the authors summarize the state of the art and future potential in the management of Osteosarcoma, Ewing's sarcoma, and Chondrosarcoma. They cover systemic therapy, surgical therapy, and radiotherapy, along with targeted therapies to inhibit signal transduction pathways. They discuss staging and the role of imaging evaluation to provide an overview of bone tumor treatment. Images presenting pathologic-radiologic correlations are included.