Primary intestinal candidiasis in an immunocompetent patient.
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Biomedical subjects
Publications and source records attributed to A Soni.
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PURPOSE: To demonstrate the feasibility of an intraoperative inverse planning technique with advanced optimization for prostate seed implantation. METHODS AND MATERIALS: We have implemented a method for optimized inverse planning of prostate seed implantation in the operating room (OR), based on the genetic algorithm (GA) driven Prostate Implant Planning Engine for Radiotherapy (PIPER). An integrated treatment planning system was deployed, which includes real-time ultrasound image acquisition, treatment volume segmentation, GA optimization, real-time decision making and sensitivity analysis, isodose and DVH evaluation, and virtual reality navigation and surgical guidance. Ten consecutive patients previously scheduled for implantation were included in the series. RESULTS: The feasibility of the technique was established by careful monitoring of each step in the OR and comparison with conventional preplanned implants. The median elapsed time for complete image capture, segmentation, GA optimization, and plan evaluation was 4, 10, 2.2, and 2 min, respectively. The dosimetric quality of the OR-based plan was shown to be equivalent to the corresponding preplan. CONCLUSION: An intraoperative optimized inverse planning technique was developed for prostate brachytherapy. The feasibility of the method was demonstrated through an early clinical experience.
PURPOSE: To develop a computer-intelligent planning engine for automated treatment planning and optimization of ultrasound- and template-guided prostate seed implants. METHODS AND MATERIALS: The genetic algorithm was modified to reflect the 2D nature of the implantation template. A multi-objective decision scheme was used to rank competing solutions, taking into account dose uniformity and conformity to the planning target volume (PTV), dose-sparing of the urethra and the rectum, and the sensitivity of the resulting dosimetry to seed misplacement. Optimized treatment plans were evaluated using selected dosimetric quantifiers, dose-volume histogram (DVH), and sensitivity analysis based on simulated seed placement errors. These dosimetric planning components were integrated into the Prostate Implant Planning Engine for Radiotherapy (PIPER). RESULTS: PIPER has been used to produce a variety of plans for prostate seed implants. In general, maximization of the minimum peripheral dose (mPD) for given implanted total source strength tended to produce peripherally weighted seed patterns. Minimization of the urethral dose further reduced the loading in the central region of the PTV. Isodose conformity to the PTV was achieved when the set of objectives did not reflect seed positioning uncertainties; the corresponding optimal plan generally required fewer seeds and higher source strength per seed compared to the manual planning experience. When seed placement uncertainties were introduced into the set of treatment planning objectives, the optimal plan tended to reach a compromise between the preplanned outcome and the likelihood of retaining the preferred outcome after implantation. The reduction in the volatility of such seed configurations optimized under uncertainty was verified by sensitivity studies. CONCLUSION: An automated treatment planning engine incorporating real-time sensitivity analysis was found to be a useful tool in dosimetric planning for prostate brachytherapy.
Approximately one third of patients with chronic hepatitis C virus (HCV) infection have normal alanine transaminase (ALT) levels. We studied the clinical, biochemical, virological, and histological features in patients with persistently normal ALT. A case-control study was conducted on 275 patients with chronic HCV infection, including 75 patients with persistently normal ALT and 200 patients with abnormal ALT. Persistently normal ALT was defined as 4 consecutive ALT values in each patient within a period of 12 months. The average age of the patients was 44 years (range 18 to 69 years). More non-Hispanic whites had persistently normal ALT. The mean serum ferritin level was significantly lower in patients with persistently normal ALT as compared with abnormal ALT (128 +/- 92 ng/mL and 224 +/- 128 ng/mL), respectively (P =.017). The mean HCV-RNA level was significantly lower in patients with persistently normal ALT as compared with abnormal ALT (12 x 10(5) +/- 2.8 x 10(6) copies/mL and 33 x 10(5) +/- 8.0 x 10(6)), respectively (P =.02). Histologically, patients with persistently normal ALT had less severe portal inflammation (P <.05), lobular inflammation (P =.003), piecemeal necrosis (P =.002), fibrosis (P <.05), lower prevalence of cirrhosis (P =.007), as well as a slower fibrosis progression rate (P <.001). Chronic hepatitis C patients with persistently normal ALT have low-activity grade and stage on liver biopsy. In these patients the hepatitis C RNA level was lower compared with abnormal ALT patients, which may explain the slower fibrosis progression rate.
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Since its discovery, radiation has been used to treat numerous ailments, including many benign conditions. The most susceptible disorders have included keloids, heterotopic bone formation, and, most recently, vascular restenosis. These disorders are proliferative in nature and fall under the category of excessive wound healing or scar formation after trauma. In addition, radiation has been used for its immunosuppressive quality, eg, in organ transplantation to suppress graft rejection and in the treatment of autoimmune diseases. In this article, we have chosen keloids as an archetype for radiation use with benign conditions; the radiation inhibition of vascular restenosis will be used as a prototype to explore a paradigm for the molecular and cellular basis of radiation treatment for selected benign disorders. Vascular restenosis is currently one of the new frontiers of radiation therapy and offers opportunities to explore the role of inflammatory or immune cell responses in benign conditions that lead to excessive fibrogenesis and require treatment. The pathophysiology of surgical wound healing has not been avidly studied in the radiobiologic laboratory setting. However, the paradigm we propose for the effectiveness of radiation treatment for benign conditions is based on the model offered by Clark. He describes three phases of molecular and cellular events in which an inflammatory phase precedes the fibrogenic phase, occurs within hours of injury, and continues for weeks. We postulate that the radiosensitive targets within the vascular milieu are the monocyte/macrophages that would otherwise act as the trigger for the induced cytokine cascade, leading to the myofibroblast being recruited from a quiescent to a proliferative phase, resulting in fibrogenesis.
Gaucher disease is an autosomal recessive inborn error of glycosphingolipid metabolism caused by the deficient activity of the lysosomal hydrolase, acid beta-glucosidase. Three phenotypically distinct subtypes result from different acid beta-glucosidase mutations encoding enzymes with absent or low activity. A severe neonatal type 2 variant who presented with collodion skin, ichthyosis, and a rapid neurodegenerative course had two novel acid beta-glucosidase alleles: a complex, maternally derived allele, E326K+L444P, and a paternally inherited nonsense mutation, E233X. Because the only other non-pseudogene-derived complex allele, D140H+E326K, also had the E326K lesion and was reported in a mild type 1 patient with a D140H+E326K/K157Q genotype, these complex alleles and their individual mutations were expressed and characterized. Because the E233X mutation expressed no activity and the K157Q allele had approximately 1% normal specific activity based on cross-reacting immunologic material (CRIM SA) in the baculovirus system, the residual activity in both patients was primarily from their complex alleles. In the type 1 patient, the D140H+E326K allele was neuroprotective, encoding an enzyme with a catalytic efficiency similar to that of the N370S enzyme. In contrast, the E326K+L444P allele did not have sufficient activity to protect against the neurologic manifestations and, in combination with the inactive E233X lesion, resulted in the severe neonatal type 2 variant. Thus, characterization of these novel genotypes with non-pseudogene-derived complex mutations provided the pathogenic basis for their diverse phenotypes.
Three skeletal muscles viz., gastrocnemius, pectoralis and diaphragm from rats acclimated to a low temperature (4 +/- 1 degrees C; 16 hr daily; maximum for 8 weeks) exhibit an increased myosin ATPase activity. An analysis of native myosin from these muscles under non-dissociating conditions reveals two myosin isozymes instead of a single isozyme expressed in control muscles. Isoelectric focusing (IEF) coupled with two dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis (2-D SDS-PAGE) confirms an increased phosphorylation of myosin light chain 2 (MLC2) in muscles from cold acclimated rats.
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We established the prevalence of gallbladder varices (GBVs) as seen on duplex sonogram of children with portal hypertension. Fifty-five consecutive children with portal hypertension underwent duplex sonographic examination by an experienced sonologist who was blinded to clinical presentation. Forty children had extrahepatic portovenous obstruction (EHPVO), 12 had cirrhosis, and three had noncirrhotic portal hypertension. GBVs were seen on sonography in 10 of 40 children with EHPVO (25%), two of 12 children with cirrhosis (16.6%), and no children with noncirrhotic portal hypertension. Sonographic findings of GBVs were confirmed on duplex sonographic imaging. Among patients with EHPVO, GBVs did not correlate with size of esophageal varices, number of sessions of sclerotherapy, presence or absence of gastric varices, portal gastropathy, or splenorenal shunt placement. In cirrhotic patients, GBVs did not correlate with Child Pugh grade. Children with EHPVO have a higher incidence of developing GBVs. The clinical significance of GBVs is their propensity to bleed during biliary surgery; thus, the operating surgeon should be made aware of them.
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