Epidemiology of keratinocyte carcinomas after organ transplantation.

Keratinocyte carcinoma (KC) is the most common type of cancer among white populations, but it is even more common among solid organ transplant recipients (OTRs). The most frequent histological type of KC among OTRs is cutaneous squamous cell carcinoma (cSCC), followed by basal cell carcinoma, although the reverse is seen in the general population. Metastatic cSCCs are more frequent, and mortality is increased compared with immunocompetent populations. There is strong evidence that the risk of KC among OTRs rises with increasing time after transplantation and older age at transplantation, and that KC is enhanced in those with sun-damaged skin. This evidence suggests that accelerated accumulation of genetic damage from several sources leads to excess KC in OTRs. We describe international variation in KC and focus on trends in immunosuppressive regimens, the role of ultraviolet susceptibility and exposure, and the contribution of genetics to tumour development. Further epidemiological studies are needed to address gaps in our understanding of the mediation of excess KC by immunosuppressive drugs, viral infection, genetic susceptibility, timing of relevant ultraviolet exposure or some combination of these factors.

Simultaneous spectrophotometric determination of celecoxib and diacerein in bulk and capsule by absorption correction method and chemometric methods.

Two methods, absorption correction and multivariate spectrophotometric methods were developed for simultaneous estimation of Celecoxib (CEL) and Diacerein (DIA) in combined dosage form. Absorption correction method involves direct estimation of DIA at wavelength 341 nm in which CEL has zero absorbance and shows no interference. For estimation of CEL, corrected absorbance was calculated at 253 nm due to the interference of DIA at this wavelength. Linearity was observed in the range of 6-22 µg mL(-1) for CEL and 3-11 µg mL(-1) for DIA. The method was validated as per ICH guidelines. Chemometric methods including classical least square (CLS), inverse least square (ILS), principal component regression (PCR) and partial least square (PLS) were studied for simultaneous determination of CEL and DIA in capsule using spectrophotometry. A set of 25 standard mixtures containing both drugs were prepared in range of 5-25 µg mL(-1) for CEL and 3-15 µg mL(-1) for DIA. Analytical figure of merit (FOM), such as sensitivity, selectivity, analytical sensitivity, limit of detection and limit of quantitation were determined for chemometric methods. The proposed methods were applied for determination of two components from combined dosage form.

Association between novel MRI-estimated pancreatic fat and liver histology-determined steatosis and fibrosis in non-alcoholic fatty liver disease.

BACKGROUND: Ectopic fat deposition in the pancreas and its association with hepatic steatosis have not previously been examined in patients with biopsy-proven non-alcoholic fatty liver disease (NAFLD). AIM: To quantify pancreatic fat using a novel magnetic resonance imaging (MRI) technique and determine whether it is associated with hepatic steatosis and/or fibrosis in patients with NAFLD. METHODS: This is a cross-sectional study including 43 adult patients with biopsy-proven NAFLD who underwent clinical evaluation, biochemical testing and MRI. The liver biopsy assessment was performed using the NASH-CRN histological scoring system, and liver and pancreas fat quantification was performed using a novel, validated MRI biomarker; the proton density fat fraction. RESULTS: The average MRI-determined pancreatic fat in patients with NAFLD was 8.5% and did not vary significantly between head, body, and tail of the pancreas. MRI-determined pancreatic fat content increased significantly with increasing histology-determined hepatic steatosis grade; 4.6% in grade 1; 7.7% in grade 2; 13.0% in grade 3 (P = 0.004) respectively. Pancreatic fat content was lower in patients with histology-determined liver fibrosis than in those without fibrosis (11.2% in stage 0 fibrosis vs. 5.8% in stage 1-2 fibrosis, and 6.9% in stage 3-4 fibrosis, P = 0.013). Pancreatic fat did not correlate with age, body mass index or diabetes status. CONCLUSIONS: In patients with NAFLD, increased pancreatic fat is associated with hepatic steatosis. However, liver fibrosis is inversely associated with pancreatic fat content. Further studies are needed to determine underlying mechanisms to understand if pancreatic steatosis affects progression of NAFLD.

Pro-inflammatory chemokine C-C motif ligand 16 (CCL-16) dysregulation in irritable bowel syndrome (IBS): a pilot study.

BACKGROUND: Irritable bowel syndrome (IBS) is a serious health problem that affects an estimated 10-15% of people worldwide and has economic consequences in the United States of over $30 billion annually. In the US, IBS affects all races and both sexes, with more females than males (2:1) reporting symptoms consistent with IBS. Although the etiology of this functional gastrointestinal disorder is unknown, literature suggests that a subclinical inflammatory component has a role in the etiologic mechanisms underlying IBS. The aim of this study was to evaluate the gene expression of inflammatory biomarkers in patients with and without IBS and among different IBS phenotypes. METHODS: Irritable bowel syndrome patients (n=12) that met Rome III Criteria for IBS longer than 6months were compared with healthy matched controls (n=12). Peripheral whole blood from fasting participants was collected and RNA was extracted. The expression of 96 inflammatory genes was then analyzed using a custom quantitative real-time PCR array. KEY RESULTS: CCL-16 gene expression was upregulated by 7.46-fold in IBS patients when compared with controls. CCL-16 was overexpressed by over 130-fold in IBS-constipation patients when compared with both controls and IBS-diarrhea patients. CONCLUSIONS & INFERENCES: These results further suggest a subclinical inflammatory component underlying IBS. To better understand the phenotypic differences in IBS it is important to broaden the study of these inflammatory and other biomarkers.

Role for endothelial nitric oxide synthase in nitrite-induced protection against renal ischemia-reperfusion injury in mice.

Nitrite is protective against renal ischemia/reperfusion injury (IRI); an effect due to its reduction to nitric oxide (NO). In addition to other reductase pathways, endothelial NO synthase (eNOS) may also facilitate nitrite reduction in ischemic environments. We investigated the role of eNOS in sodium nitrite (60 microM, 10 ml/kg applied topically 1 min before reperfusion)-induced protection against renal IRI in C57/BL6 wild-type (WT) and eNOS knockout (eNOS KO) mice subjected to bilateral renal ischemia (30 min) and reperfusion (24h). Markers of renal dysfunction (plasma [creatinine] and [urea]), damage (tubular histology) and inflammation (cell recruitment) were elevated following IRI in WT mice; effects significantly reduced following nitrite treatment. Chemiluminescence analysis of cortical and medullary sections of the kidney demonstrated rapid (within 1 min) distribution of nitrite following application. Whilst IRI caused a significant (albeit substantially reduced compared to WT mice) elevation of markers of renal dysfunction and damage in eNOS KO mice, the beneficial effects of nitrite were absent or reduced, respectively. Moreover, nitrite treatment enhanced renal dysfunction in the form of increased plasma [creatinine] in eNOS KO mice. Confirmation of nitrite reductase activity of eNOS was provided by demonstration of nitrite (100 microM)-derived NO production by kidney homogenates of WT mice, that was significantly reduced by L-NMMA. L-NMMA was without effect using kidney homogenates of eNOS KO mice. These results support a role for eNOS in the pathways activated during renal IRI and also identify eNOS as a nitrite reductase in ischemic conditions; activity which in part underlies the protective effects of nitrite.

The diagnostic value of abdominal ultrasound, urine cytology and prostate-specific antigen testing in the lower urinary tract symptoms clinic.

INTRODUCTION: Lower urinary tract symptoms (LUTS) affect 18-26% of men aged 40-79 years, many of whom present with a fear of having cancer. Current guidelines for the assessment of LUTS focus mainly upon benign prostatic hypertrophy. It has been our practice to perform an abdominal ultrasound scan (USS), a prostate-specific antigen (PSA) blood test and urine cytology during the assessment of males presenting with LUTS to investigate the alternative potentially life-threatening causes for LUTS. We report on the added value of these tests during the assessment of men with LUTS. RESULTS: A total of 263/3976 (6.6%) patients investigated for LUTS were found to have incidental urological malignancies, urinary tract calculi or abdominal aortic aneurysms (AAA). Abdominal USSs resulted in the incidental diagnosis of four renal carcinomas (0.1%), 45 AAAs (incidence = 1.1%) and 44 urinary tract calculi (1.1%). Urine cytology testing and bladder USSs helped diagnose 17 new bladder cancers (0.4%), five of which did not present with haematuria. Patients found to have an elevated age-specific PSA had a 23.6% chance of being diagnosed with prostate cancer (3.8%). CONCLUSION: The addition of abdominal ultrasound scanning, urine cytology and PSA testing as part of an LUTS assessment protocol can help to diagnose significant, potentially life-threatening conditions in up to 6.6% of patients. While the pick up rate of each individual condition is not higher in the LUTS patient than in the general population, the combined pick up rate may justify these additional investigations.

Magnetic resonance imaging may simulate progressive multifocal leucoencephalopathy in a patient with chronic lymphocytic leukemia after fludarabine therapy.

A 60-year-old male with chronic lymphatic leukemia (CLL) after 6 months of fludarabine therapy was admitted with status epilepticus and developed left hemiplegia. His magnetic resonance imaging revealed multiple T2 hyperintense lesions in the right frontal and left parieto-occipital lesion, simulating progressive multifocal leucoencephalopathy (PML). Cerebrospinal fluid Polymerase Chain Reaction (PCR) for JC virus was negative. We suggest the possible role of fludarabine in producing PML-like lesions in patients with Chronic Lymphocytic Leukemia (CLL).

The use of cylindrical coordinates for treatment planning parameters of an elongated 192Ir source.

PURPOSE: The doses given to the intima, media, and adventitia are very crucial quantities in intravascular brachytherapy. To facilitate accurate computerized treatment planning calculations, we have determined dose distributions in away-and-along table format around an 192Ir wire source and developed pertinent dosimetric parameters in cylindrical coordinates. METHODS AND MATERIALS: The Monte Carlo method (MCNP4C code) was used to calculate the dose distributions for the AngioRad 192Ir wire source (model SL-77HS, Interventional Therapies). The calculations were carried out for photon, beta, and electron (conversion and Auger) contributions for radial distances from 0.03 to 2.0 cm with 0.01-cm increments, and up to 2.24 cm from the source center in the longitudinal direction with 0.04-cm resolution. Dose rate values are determined in away-and-along format (cylindrical coordinates) and then converted to spherical coordinate format. Dosimetric parameters, such as the geometry factor, G(r, theta), and anisotropy function, F(r, theta), are generated in both cylindrical (R, Z, phi) and spherical (r, theta, phi) coordinates. The use of a cylindrical coordinate system for treatment planning parameters is proposed as a more suitable approach for accurate calculations. RESULTS: The photon contribution to dose varies nearly inversely with radial distance (from the source center) along the perpendicular bisector with 0.199 x 10(-3) cGy U(-1) s(-1) (0.802 cGy Ci(-1) s(-1)) at 1 cm. The beta and electron contributions start at very high values of about 35.5 x 10(-3) cGy U(-1) s(-1) and 11.0 x 10(-3) cGy U(-1) s(-1), respectively, at 0.03 cm and fall off exponentially to negligible amount near 0.2 cm. The total dose rate at 0.2 cm is 1.428 x 10(-3) cGy U(-1) s(-1) (5.754 cGy Ci(-1) s(-1)). The radial dose function, g(R), is nearly unity between 0.2 cm and 2 cm. Due to the beta and electron dose contributions, g(R) increases steeply to 5.5 as radial distance decreases from 0.2 cm down to 0.03 cm. The F(R, Z) values are close to unity for the majority of the region of interest. In contrast, F(r, theta) experiences a steep rise as shallow angles are approached (closer to the source), related to the beta dose contributions. Accurate treatment planning calculations would be possible with linear interpolation of F(R, Z), but difficult with F(r, theta) in the spherical coordinate system and the original normalization point as recommended in the American Association of Physicists in Medicine Task Group 60 (AAPM TG-60) formalism. CONCLUSION: The AngioRad 192Ir wire source, model SL-77HS, was completely characterized dosimetrically using Monte Carlo methods. The use of cylindrical coordinates and a modified anisotropy function normalization point for dosimetric parameters of an elongated 192Ir source is more suitable for accurate computerized treatment planning calculations in intravascular brachytherapy.

Thermoluminescent dosimetry of the Symmetra 125I model I25.S06 interstitial brachytherapy seed.

As the efficacy of brachytherapy prostate treatment is becoming realized, new models of 125I seeds are being introduced. In this article we present thermoluminescent dosimetry (TLD) in a solid water phantom for a new design of 125I seed (UroMed/Bebig Symmetra, Model I25.S06). TLD cubes, LiF TLD-100, from Bicron (Solon, OH) with dimension 1 x 1 x 1 mm3 were irradiated at various distances from the seed at angles ranging from 0 degrees to 90 degrees in 10 degrees increments. The TLD detectors were calibrated by irradiation in a 60Co teletherapy beam. Monte Carlo simulation was used to account for TLD energy dependence and the deviation of solid water composition (as determined by chemical analysis of a sample) from liquid water. Dose rates per unit air kerma strength were determined based on calibrations traceable to the 1999 NIST standard (corrected for NIST measurement errors made in 1999) for the Symmetra seed. Dose data is presented in TG-43 format as a function of distance and angle. Values for lambda, F(r, theta), g(r), and the anisotropy constant are obtained for use in radiation treatment planning (RTP) software. The dose rate constant was determined to be 1.033+/-6.4% cGy h(-1) U(-1), which is comparable to model 6702 and higher than model 6711. We find the relative dose distributions of the Symmetra seed are similar to model 6702, and less anisotropic than model 6711. After accounting for deviation of measured solid water composition from the manufacturer's specification, good agreement between TLD results and Monte-Carlo-aided values was found.

Aspergillus fumigatus infection in a mega prosthetic total knee arthroplasty: salvage by staged reimplantation with 5-year follow-up.

Fungal infection after total joint arthroplasty is an extremely serious complication and a challenge to the treating physician. When a fungal infection is compounded by a massive allograft or a metallic segmental replacement of the femur or other long bone, treatment options become increasingly limited and commonly have led to arthrodesis or amputation of the infected limb. We present the first case report of a low-grade osteosarcoma treated with a segmental distal femoral allograft prosthetic composite knee arthroplasty, which was complicated by infection with Aspergillus fumigatus. This complication was treated successfully with a staged reimplantation procedure, intravenous amphotericin, and oral fluconazole suppression. At 5 years after reimplantation, the patient has had no evidence of infection, no pain, and excellent range of motion without extensor lag. The Knee Society knee score improved from 50 to 100, and the function score improved from 40 to 100 (for both scores, 100 is the maximum).

Treatment planning dosimetric parameters for a (90)Y coil source used in intravascular brachytherapy.

BACKGROUND: (90)Y coil sources have been used in animal and clinical trials for treatment of restenosis in intravascular brachytherapy (IVBT). This study aims to determine the American Association of Physicists in Medicine (AAPM) Task Group-60 (TG-60) dosimetric quantities in regions surrounding the balloon wall for use in treatment planning computer systems. METHODS: The Monte Carlo method was used to determine the dose distribution, using MCNP4B2 code. The coil source was modeled by a hollow cylinder of 2.9 cm length centered in a balloon (2.5 mm diameter) filled with carbon dioxide (CO(2)) at 5 atm. Scoring voxels consisted of contiguous annular disk shells with 0.1 mm spacing in the radial direction and 0.2 mm spacing in the longitudinal direction. The scoring region ranges from the center of the source to 1.0 cm in the longitudinal direction, and from 0.13 to 1 cm in the radial direction. In the plane containing the source axis, the Monte Carlo-generated doses in rectilinear coordinates are converted to polar coordinates. RESULTS: The dose rate of the source is provided in both Cartesian and polar coordinates. The dose rate constant [D(r(0),theta(0))], anisotropy function [F(r,theta)], and radial dose function [g(r)] were generated from these values and listed in tabular format. At shallow angles and longer distances from the source center, large values of the anisotropy function resulted, deviating two orders of magnitude from unity. CONCLUSIONS The doses given to the intima, media, and adventitia are very crucial quantities in IVBT. The calculated TG-60 dosimetric quantities, used commonly in conventional brachytherapy applications, provide a means for the user to determine the three-dimensional dose surrounding the balloon catheter. These parameters can be used in future treatment planning system for IVBT. We also discuss the need to develop a new formalism specific to longer sources used in IVBT.

A new treatment planning formalism for catheter-based beta sources used in intravascular brachytherapy.

Intravascular brachytherapy (IVBT) is an emerging modality for the treatment of atherosclerotic lesions in the artery. As part of the refinement in this rapidly evolving modality of treatment, the current simplistic dosimetry approach based on a fixed-point prescription must be challenged by future rigorous dosimetry method employing image-based three-dimensional (3D) treatment planning. The goals of 3D IVBT treatment planning calculations include (1) achieving high accuracy in a slim cylindrical region of interest, (2) accounting for the edge effect around the source ends, and (3) supporting multiple dwell positions. The formalism recommended by Task Group 60 (TG-60) of the American Association of Physicists in Medicine (AAPM) is applicable for gamma sources, as well as short beta sources with lengths less than twice the beta particle range. However, for the elongated beta sources and/or seed trains with lengths greater than twice the beta range, a new formalism is required to handle their distinctly different dose characteristics. Specifically, these characteristics consist of (a) flat isodose curves in the central region, (b) steep dose gradient at the source ends, and (c) exponential dose fall-off in the radial direction. In this paper, we present a novel formalism that evolved from TG-60 in maintaining the dose rate as a product of four key quantities. We propose to employ cylindrical coordinates (R, Z, phi), which are more natural and suitable to the slim cylindrical shape of the volume of interest, as opposed to the spherical coordinate system (r, theta, phi) used in the TG-60 formalism. The four quantities used in this formalism include (1) the distribution factor, H(R, Z), (2) the modulation function, M(R, Z), (3) the transverse dose function, h(R), and (4) the reference dose rate at 2 mm along the perpendicular bisector, D(R0=2 mm, Z0=0). The first three are counterparts of the geometry factor, the anisotropy function and the radial dose function in the TG-60 formalism, respectively. The reference dose rate is identical to that recommended by TG-60. The distribution factor is intended to resemble the dose profile due to the spatial distribution of activity in the elongated beta source, and it is a modified Fermi-Dirac function in mathematical form. The utility of this formalism also includes the slow-varying nature of the modulation function, allowing for more accurate treatment planning calculations based on interpolation. The transverse dose function describes the exponential fall-off of the dose in the radial direction, and an exponential or a polynomial can fit it. Simultaneously, the decoupling nature of these dose-related quantities facilitates image-based 3D treatment planning calculations for long beta sources used in IVBT. The new formalism also supports the dosimetry involving multiple dwell positions required for lesions longer than the source length. An example of the utilization of this formalism is illustrated for a 90Y coil source in a carbon dioxide-filled balloon. The pertinent dosimetric parameters were generated and tabulated for future use.

Ytterbium-169: a promising new radionuclide for intravascular brachytherapy.

PURPOSE: To explore the feasibility of 169Yb (gamma, 93 keV) as a new radionuclide for intravascular brachytherapy (IVBT) in terms of dose distribution, penetration power, and radiation safety features as compared with 125I and 192Ir. METHODS: The dose distributions for catheter-based sources, 169Yb, 125I, and 192Ir, in homogeneous water and in the presence of calcium and a steel stent have been determined and compared using the Monte Carlo method (MCNP4B2 code). The dose rates of the sources were evaluated from 0.02 to 100 cm. RESULTS: In the short distance range (0.02

Effect of stent on radiation dosimetry in an in-stent restenosis model.

PURPOSE: Intravascular brachytherapy is the leading modality being evaluated for treatment of in-stent restenosis. Stent struts may have an effect on the dose distributions of various radiation sources. We evaluated dosimetry in a stented coronary artery model using a variety of beta and gamma sources and stent materials. METHODS: We determined the dose distributions with and without stent in the in-stent restenosis model. Three beta-particle emitting radionuclides, 90Y (2.3 MeV), 144Pr (3.0 MeV), and 106Rh (3.5 MeV), and two gamma-ray emitters, 192Ir (380 keV) and 125I (30 keV), were studied. Stent materials included stainless steel, nitinol, and tantalum. Monte Carlo dose calculations were performed in a stent model of multiple stent struts placed at 1.5 mm from the source. Isodose curves were generated and the ratios of dose rates with and without stent, the stent factors, were evaluated. A stent factor of greater or less than unity represents dose enhancement or reduction in the presence of a stent. RESULTS: For the three beta radionuclides, dose reduction was found on the adventitial side of the stent strut and dose enhancement was noted on the luminal side. On the luminal side, the maximum dose enhancement ranges from 7% to 29%, and the dose reduction on the adventitial side ranges from 13% to 43%. Both the reduction and enhancement effects were most pronounced for the high atomic number material, tantalum. For a given stent material, the dose reduction and enhancement are similar for the three beta radionuclides. For the gamma sources, the stent had no effect for the high-energy 192Ir, but for the low-energy 125I, drastic dose reduction on the adventitial side was observed (up to 86% for tantalum stent), and about 10% dose enhancement on the luminal side was also noted. The dose reduction with 125I was more pronounced than that seen with the beta sources. CONCLUSIONS: The presence of stent struts significantly affects dose distributions of 90Y, 106Rh, 144Pr, and 125I. The maximum dose reduction can be as much as 86%. 192Ir was unaffected. These factors need to be considered in choosing radionuclides and dose prescriptions in treating in-stent restenosis.

Interferometric all-optical switches for ultrafast signal processing.

All-optical switches find applications in ultrahigh-speed network-user interfaces and in specialized high-speed processors, such as data regenerators and encryptors and microwave signal generators. We describe a semiconductor optical-amplifier-based single-arm interferometric switch called the ultrafast nonlinear interferometer. We discuss how the gain and the refractive-index nonlinearities in semiconductor optical amplifiers have an impact on the all-optical switch design, and we review experimental results obtained with the ultrafast nonlinear interferometer.

40-Gbitys cascadable all-optical logic with an ultrafast nonlinear interferometer.

We demonstrate 40-Gbitys all-optical bitwise inversion and wavelength conversion, using an ultrafast nonlinear interferometer. This device uses optically induced gain and index nonlinearities in a semiconductor amplifier to achieve the high-rate switching. The device is cascadable and can be configured to perform a variety of switching functions. As an example, 10-Gbitys results of OR and NOR gating are presented.

AIDS in the workplace: current practices and possible implications.

The testing of Acquired Immune Deficiency Syndrome (AIDS) remains a political factor. Questions are being raised as to an individual's right to privacy and the public's concern for safety. Despite the controversy, the law protects contagious disease sufferers from employment discrimination. Along with AIDS testing, drug testing remains a controversial issue. Mandatory drug testing remains in both the public and private sectors. Legislative activity in California continues to the present.