McSART: an iterative model-based, motion-compensated SART algorithm for CBCT reconstruction.

4D cone beam computed tomography (CBCT) images of the thorax and abdomen can have reduced quality due to the limited number of projections per respiratory bin used in gated image reconstruction. In this work, we present a new algorithm to reconstruct high quality CBCT images by simultaneously reconstructing images and generating an associated respiratory motion model. This is done by updating model parameters to compensate for motion during the iterative image reconstruction process. CBCT image acquisition was simulated using the digital eXternal CArdiac Torso (XCAT) phantom, simulating breathing motion using four patient breathing traces. 4DCBCT images were reconstructed using the simultaneous algebraic reconstruction technique (SART), and compared to the proposed motion-compensated SART (McSART) algorithm. McSART used a motion model that describes tissue position as a function of diaphragm amplitude and velocity. The McSART algorithm alternately updated the motion model and image reconstruction, increasing the number of projections used for image reconstruction with every iteration. The model was able to interpolate and extrapolate deformations according to the magnitude of the surrogate signal. Without noise, the final iteration McSART images had HU errors at 31%, 34%, and 44% of their SART-reconstructed counterparts compared to ground truth XCAT images, with corresponding root-mean-square (RMS) motion model errors of 0.75 mm, 1.08 mm, and 1.17 mm respectively. With added image noise, McSART's HU error was 31% of the SART-reconstructed 4DCBCT error, with a 1.43 mm RMS motion model error. Qualitatively, blurring and streaking artifacts were reduced in all the reconstructed images compared to 3D or SART-reconstructed 4DCBCT. The output of the algorithm was a high quality reference image and a corresponding motion model, that could be used to deform the reference image to any other point in a breathing cycle.

Tobacco and other factors have a negative impact on quality of life in hepatitis C patients.

Hepatitis C virus (HCV) is known to adversely affect general, social, emotional and mental health domains. This study was designed to identify variables that may be associated with these measurable outcomes. We conducted a cross-sectional retrospective review of demographic and clinical data from 800 patients with HCV evaluated between January 1998 and November 2007. Data were collected using a standardized questionnaire filled out by the patients at the first encounter. Variables evaluated included fibrosis stages (i.e. FS0/1/2 vs FS3/4), demographics, comorbid health conditions, tobacco and alcohol use, high-risk social behaviours and laboratory data. Variables assessed were depression, fatigue, problems sleeping and loss of interest in sex. Statistical analysis was performed using univariate and multivariate logistic regression. Depression (29.3%) in our HCV study population was associated with female gender, tobacco use, hyperlipidemia, history of heavy alcohol use and intravenous drug use. Fatigue (44.6%) was associated with end-stage renal disease, past and current tobacco use and current alcohol use. Difficulty sleeping (13.8%) was associated with past and current tobacco use, current alcohol use and diabetes. Loss of interest in sex (7.7%) was associated with current tobacco use, multiple risk factors for HCV and age at time of evaluation. Fibrosis stage (FS) also had a significant positive association with alcohol use (OR 2.61; P = 0.003) and tobacco use (OR 2.00; P = 0.002). Smoking and alcohol use have a significant negative impact on the presence of depression, fatigue, difficulty sleeping and loss of interest in sex in HCV patients. Practitioners should be aware of these associations, particularly tobacco use, which significantly and negatively impacted every variable evaluated.

Infections of the external ear.

Otitis externa is one of the most common conditions seen in the otolaryngology practice. It encompasses a wide range of conditions, from those that cause mild inflammation and discomfort to those that are life-threatening. The management of these conditions requires a clear understanding of the anatomy and physiology of the ear canal, the microbiology of pathogens and familiarity with the clinical presentation.

Integrating polymerase chain reaction, valving, and electrophoresis in a plastic device for bacterial detection.

An integrated plastic microfluidic device was designed and fabricated for bacterial detection and identification. The device, made from poly(cyclic olefin) with integrated graphite ink electrodes and photopatterned gel domains, accomplishes DNA amplification, microfluidic valving, sample injection, on-column labeling, and separation. Polymerase chain reaction (PCR) is conducted in a channel reactor containing a volume as small as 29 nL; thermal cycling utilizes screen-printed graphite ink resistors. In situ gel polymerization was employed to form local microfluidic valves that minimize convective flow of the PCR mixture into other regions. After PCR, amplicons (products) are electrokinetically injected through the gel valve, followed by on-chip electrophoretic separation. An intercalating dye is admixed to label the amplicons; they are detected using laser-induced fluorescence. Two model bacteria, Escherichia coli O157 and Salmonella typhimurium, were chosen to demonstrate bacterial detection and identification based on amplification of several of their unique DNA sequences. The limit of detection is about six copies of target DNA.

Persistent organic pollutants in the dusts that settled across lower Manhattan after September 11, 2001.

The explosion and collapse of the World Trade Center (WTC) was a catastrophic event that produced an aerosol impacting many workers, residents, and commuters during the first few days after September 11, 2001. During the initial days that followed, 14 bulk samples of the settled dust were collected at locations surrounding the epicenter of the disaster, including one indoor location. Some samples were analyzed for many potential hazards, including inorganic and organic constituents as well as morphology. The results of the analyses for persistent organic pollutants are described herein, including polycyclic aromatic hydrocarbons, polychlorinated biphenyls, and select organochlorine pesticides on settled dust samples. The sigma86-PCBs comprising less than 0.001% by mass of the bulk in the three bulk samples analyzed indicated that PCBs were of limited significance in the total settled dust across lower Manhattan. Likewise, organochlorine pesticides, including chlordanes, hexachlorobenzene, heptachlor, 4,4'-DDE, 2,4'-DDT, 4,4'-DDT, and Mirex, were found at low concentrations in the bulk samples. Conversely, the sigma37-PAHs comprised up to nearly 0.04% (<0.005-0.039%) by mass of the bulk settled dust in the six bulk samples. Further size segregation of these three initial bulk samples and seven additional samples indicates that sigma37-PAHs were found in higher concentrations on relatively large particles (10-53 microm), representing up to 0.04% of the total dust mass. Significant concentrations were also found on fine particles (<2.5 microm), often accounting for approximately 0.005% by mass. We estimate that approximately 100-1000 tons of sigma37-PAHs were spread over a localized area immediately after the WTC disaster on September 11.

Synthesis and biological activity of a photoaffinity etoposide probe.

The epipodophyllotoxin etoposide is a potent and widely used anticancer drug that targets DNA topoisomerase II. The synthesis, photochemical, and biological testing of a photoactivatable aromatic azido analogue of etoposide also containing an iodo group is described. This azido analogue should prove useful for identifying the etoposide interaction site on topoisomerase II. Irradiation of the azido analogue and an aldehyde-containing azido precursor with UV light produced changes in their UV--visible spectra that were consistent with photoactivation. The azido analogue strongly inhibited topoisomerase II and inhibited the growth of Chinese Hamster Ovary cells. Azido analogue-induced topoisomerase II--DNA covalent complexes were significantly increased subsequent to UV irradiation of drug-treated human leukemia K562 cells as compared to etoposide-treated cells. These results suggest that the photoactivated form of etoposide is a more effective topoisomerase II poison either by interacting directly with the enzyme or with DNA subsequent to topoisomerase II-mediated strand cleavage.

Transsphenoidal pituitary surgery in Cushing's disease: can we predict outcome?

OBJECTIVE: To assess the results of transsphenoidal pituitary surgery in patients with Cushing's disease over a period of 18 years, and to determine if there are factors which will predict the outcome. PATIENTS: Sixty-nine sequential patients treated surgically by a single surgeon in Newcastle upon Tyne between 1980 and 1997 were identified and data from 61 of these have been analysed. DESIGN: Retrospective analysis of outcome measures. MAIN OUTCOME MEASURES: Patients were divided into three groups (remission, failure and relapse) depending on the late outcome of their treatment as determined at the time of analysis, i.e. 88 months (median) years after surgery. Remission is defined as biochemical reversal of hypercortisolism with re-emergence of diurnal circadian rhythm, resolution of clinical features and adequate suppression on low-dose dexamethasone testing. Failure is defined as the absence of any of these features. Relapse is defined as the re-emergence of Cushing's disease more than one year after operation. Clinical features such as weight, sex, hypertension, associated endocrine disorders and smoking, biochemical studies including preoperative and postoperative serum cortisol, urine free cortisol, serum ACTH, radiological, histological and surgical findings were assessed in relation to these three groups to determine whether any factors could reliably predict failure or relapse after treatment. RESULTS: Of the 61 patients included in this study, 48 (78.7%) achieved initial remission and 13 (21.3%) failed treatment. Seven patients suffered subsequent relapse (range 22-158 months) in their condition after apparent remission, leaving a final group of 41 patients (67.2%) in the remission group. Tumour was identified at surgery in 52 patients, of whom 38 achieved remission. In comparison, only 3 of 9 patients in whom no tumour was identified achieved remission. This difference was significant (P = 0.048). When both radiological and histological findings were positive, the likelihood of achieving remission was significantly higher than if both modalities were negative (P = 0.038). There were significant differences between remission and failure groups when 2- and 6-week postoperative serum cortisol levels (P = 0.002 and 0.001, respectively) and 6-week postoperative urine free cortisol levels (P = 0.026) were compared. This allowed identification of patients who failed surgical treatment in the early postoperative period. Complications of surgery included transitory DI in 13, transitory CSF leak in 8 and transitory nasal discharge and cacosmia in 3. Twelve of 41 patients required some form of hormonal replacement therapy despite achieving long-term remission. Thirteen patients underwent a second operation, of whom 5 achieved remission. CONCLUSIONS: Transsphenoidal pituitary surgery is a safe method of treatment in patients with Cushing's disease. Operative findings, radiological and histological findings, together with early postoperative serum cortisol and urine free cortisol estimates may identify failures in treatment. Alternative treatment might then be required for these patients. Because of the risk of late relapse, patients require life-long follow-up.

The catalytic DNA topoisomerase II inhibitor dexrazoxane (ICRF-187) induces endopolyploidy in Chinese hamster ovary cells.

The bisdioxopiperazines, including dexrazoxane (ICRF-187), are catalytic or noncleavable complex-forming inhibitors of DNA topoisomerase II that do not produce DNA strand breaks. In this study we show that dexrazoxane inhibits the division of Chinese hamster ovary (CHO) cells resulting in marked increases in cell size (up to 80 microm in diameter), volume (up to 150-fold greater), and ploidy (as high as 32N). This last result indicates that the dexrazoxane-induced DNA reduplication was restricted to once per cell cycle. Kinetic analysis of the flow cytometry data indicated that the conversion between successively higher ploidy levels was progressively slowed at longer times of exposure to dexrazoxane. Both the protein and DNA content of dexrazoxane-treated CHO cells increased linearly over time in the same proportion. Light and electron microscopic studies of dexrazoxane-treated cells showed ring-like multilobulated nuclei. Immunohistochemical staining of dexrazoxane-treated cells showed that F-actin and acetylated alpha-tubulin were present in large, highly organized networks. Immunohistochemical staining of the dexrazoxane-treated CHO cells also showed that the topoisomerase II alpha colocalized with the DNA of the multilobulated nuclei. Staining of gamma-tubulin revealed that the dexrazoxane-treated cells contained multiple centrosomes, indicating that dexrazoxane prevents cytokinesis but not centrosome reduplication. It is concluded that dexrazoxane inhibits CHO cytokinesis in cells by virtue of its ability to inhibit topoisomerase II.

Squamous cell carcinoma of the temporal bone: diagnosis, treatment and prognosis.

Squamous cell carcinoma of the external ear canal is an uncommon condition that is associated with a poor outcome. The development of an accepted staging system has not been forthcoming and this has inhibited the formation of an evidence-based therapeutic protocol. We report the findings in 14 patients with squamous cell carcinoma of the external ear canal treated in our institutions. The most common presenting symptoms were otorrhoea and otalgia. Four patients had a history of chronic ear discharge and one had previous radiotherapy for nasopharyngeal carcinoma. Five patients had facial palsy which was a poor prognostic sign. Only one patient had clinical neck disease. Pre-operative imaging with CT or MRI scans was accurate in determining the extent of tumour involvement. The initial T-staging relied heavily on these findings. With combination treatment involving surgery, radiotherapy and chemotherapy, disease free survival achieved was 69% (9 of 13) over a mean follow-up period of 24.7 months. One patient absconded treatment. Patients with early stage tumours faired better than patients with advanced tumours (100% vs 33%). There was low incidence of involvement of the parotid gland (1 of 7 patients). Patients with facial nerve involvement had a significantly poorer outcome (p = 0.035).

Facial nerve grading systems.

Clinicians require a reliable and sensitive facial grading system to determine the status of facial nerve function postinjury as well as to evaluate the efficacy of treatment outcomes. The method of assessment should be easy to administer, reproducible, clinically relevant, and require little time and expense. The grading system should be sufficiently sensitive to detect changes over time or following treatment. The lack of a universally accepted grading system frequently does not allow meaningful comparison when assessing the effectiveness of treatment protocols for facial nerve injury. The aim of this article is to review most of the previously published facial grading systems. It is our contention that a grading system developed and currently used within our institution appropriately addresses the needs as well as many of the deficiencies of most other grading systems.

Optical fiber biosensor for the determination of low biochemical oxygen demand.

An optical fiber biosensor was developed for the evaluation of low Biochemical Oxygen Demand (BOD) values in river waters. Artificial wastewater (AWW) solution was employed as standards for the calibration of the BOD sensor. The response time of the sensor was 15 min, and the optimal BOD response was observed at 30 degrees C, pH 7.0. A linear relationship was obtained between the output voltage and BOD5 values, and the range of determination was 1-10 mg l(-1) BOD. The sensor response was almost not influenced by chloride ion up to 1000 mg l(-1), and also not affected by heavy metal ions (Fe3+, Cu2+, Mn2+, Cr3+, Zn2+). The BOD of river waters was estimated by using the optical fiber biosensor, and good correlation between the sensor and BOD5 test was obtained (r2 = 0.971).

The cardioprotective and DNA topoisomerase II inhibitory agent dexrazoxane (ICRF-187) antagonizes camptothecin-mediated growth inhibition of Chinese hamster ovary cells by inhibition of DNA synthesis.

Dexrazoxane (ICRF-187), which is clinically used to reduce doxorubicin-induced cardiotoxicity, has cell growth inhibitory properties through its ability to inhibit the catalytic activity of DNA topoisomerase II. A study was undertaken to investigate whether preincubating Chinese hamster ovary cells (CHO) with dexrazoxane prior to camptothecin treatment resulted in potentiation. Camptothecin is a DNA topoisomerase I poison. It was found that pretreating CHO cells with concentrations of dexrazoxane sufficient to strongly inhibit topoisomerase II for periods from 18 to 96 h resulted in significant antagonism of camptothecin-mediated growth inhibition. Lower concentrations that were sufficient to cause partial inhibition of topoisomerase II and partial dexrazoxane-mediated cell growth inhibition had little effect on camptothecin-mediated growth inhibition. Neither topoisomerase I protein levels nor camptothecin-induced topoisomerase I-DNA covalent complexes were affected by dexrazoxane concentrations that were sufficient to cause antagonism of camptothecin-induced growth inhibition. However, under these experimental conditions, dexrazoxane caused a decrease in DNA synthesis. Therefore, results presented here confirm the importance of the DNA synthesis-dependent replication fork interaction with topoisomerase I-DNA covalent complexes for the expression of camptothecin activity. It is concluded that dexrazoxane and camptothecin analogs should be used with caution in combination chemotherapy.

Reproducible and high-speed separation of basic drugs by capillary zone electrophoresis.

The complete separation of a mixture of seventeen basic drugs of different classes was achieved with capillary zone electrophoresis in 11 min. The migration time reproducibility for individual components was between 0.5 and 1.7% relative standard deviation (R.S.D.). Peak detection was achieved by ultraviolet absorption, with peak-area reproducibility ranging from 1.5 to 6.3% R.S.D. The pH of the running buffer was critical in determining the separation of the mixture of basic drugs. The detection of most of these components in urine and plasma is also illustrated.

Strain-specific differences in surface antigens of symbiotic algae.

Intracellular symbiotic dinoflagellates (zooxanthellae) isolated from different invertebrate hosts are morphologically similar but could be differentiated by the fluorescent-antibody technique.