Technical Note: The development of a multi-physics simulation tool to estimate the background dose by systemic targeted alpha therapy.

PURPOSE: To predict biological effects of targeted alpha therapy (TAT) in preclinical studies, dosimetry calculations based on the micro-level distributions of emitters are essential. Due to the saturation of the tumor antigenic sites and bonding breaks by decay, some of Alpha-immuno-conjugate and decay daughters may inevitably be transported by convection and diffusion along with blood or lymphatic circulation. This results in highly nonuniform and unsteady distributions of irradiation sources. Since the micro-level distribution of emitters cannot be measured and obtained in patients with current technology, a modeling toolset to give more insight of the internal dose could be an alternative. METHODS: A multi-physics model based on a Monte Carlo microdosimetry technique and computational fluid dynamics (CFD) modeling was developed and applied to multiple internal irradiation sources. The CFD model tracks the path of the radionuclides and the dose model is capable of evaluating the time-dependent absorbed dose to the target. RESULTS: The conceptual model is capable of handling complex nonuniform irradiation sources in vasculature. The results from the simulations indicate that the assumption of homogeneous and motionless distribution of the administered activity used in the conventional dose calculation tends to significantly underestimate or overestimate the absorbed dose to the vascular system in various scenarios. CONCLUSION: Modeling the in vivo transport of radionuclides has the potential to improve the accuracy of TAT dose estimates. It could be the first step to develop a simulation tool set for assessing absorbed dose to tumor or normal tissues and predict the corresponding biological responses in the future.

Do adipofascial flaps affect the mechanical properties of a repaired tendon? A biomechanical rat model study.

The aim of this study was to evaluate the effect of vascularized and non-vascularized fascial flaps on tendon healing, specifically the maximum strain, maximum stress, elasticity and resistance of the repaired tendon. Rats were randomly divided into 3 groups: Group 1 - primary repair; Group 2 - vascularized pedicled fascial graft; Group 3 - non-vascularized free fascial graft. The rats were euthanized after 2 weeks and 40mm-long samples were taken from the Achilles tendon and gastrocnemius muscle. To evaluate the mechanical properties of the tendons, maximum load, maximum deformation, energy stored until yield point and stiffness on the load-deformation curve were measured. Based on this mechanical testing, the best group in terms of tissue strength and quality was the primary repair group. When the samples were examined individually, the two samples with the highest breaking force after the control group were in the pedicled graft group. The worst results overall were in the free graft group. We believe that if the blood flow is preserved for the fascial flap in the pedicled graft group, the tendon's breaking force would be higher.

Determinants of felt stigma in epilepsy.

The present study aimed to determine the level of felt stigma, overprotection, concealment, and concerns related to epilepsy in different life domains by using culturally-specific scales for Turkish individuals with epilepsy. Also, it aimed to detect relations among the study variables and to determine the variables which predict felt stigma. For this purpose, felt stigma scale, overprotection scale, concealment of epilepsy scale, and concerns of epilepsy scale were administered to two hundred adult persons with epilepsy (PWE). The results showed that almost half of the participants reported felt stigma, overprotection, concealment of epilepsy, concerns related to future occupation, and concerns related to social life. Almost all the study variables show correlations with each other. Concealment of epilepsy, concerns related to social life, and concerns related to future occupation were found as the predictors of felt stigma.

Intrinsically conducting polymer nanowires for biosensing.

Nanomaterials are commonly exploited to increase the sensitivity of sensors. Conductive polymers are emerging as promising sensing materials as they are easy to functionalize with the appropriate sensing probes, and also act as signal transducers. By constraining the material into one dimensional nanowires, extraordinary sensitivity is achieved. This review deals with the fabrication of these electrically conductive polymer nanowire (ECPNW) sensors and their use for detecting nucleic acid sequences, proteins and pathogens.

Predictors of positive and negative attitudes toward their condition in Turkish individuals with epilepsy.

The purpose of this cross-sectional study was to explore the attitudes of individuals with epilepsy (IWE) toward their condition via self-reported changes in the feelings/thoughts about having epilepsy. We aimed to investigate whether individuals with epilepsy perceive a change in their initial attitudes toward the condition over time. Additionally, if a change was perceived, the variables which predict the current thoughts/feelings toward epilepsy were also examined. Seventy adult IWE participated in the study. Of the 70 participants in the study, 25.7% retained their initial feelings/thoughts without any change. Among the IWE who reported no-change, the most common category was "negative from the beginning". On the other hand, 74.3% of the participants reported a change. Of the 74.3% of participants reporting change, the most common direction was from negative to positive" (79.2%) seeming to indicate a positive adjustment over the passage of time. In a logistic regression, only three factors were found to predict positive feelings/thoughts toward epilepsy: a clear understanding of the condition, low levels of depression and current employment status. Finally, there is a discussion of the potential applications of the IWE' self-assessment of their attitudes.

Antimutagenicity of amifostine against the anticancer drug fotemustine in the Drosophila somatic mutation and recombination (SMART) test.

Amifostine (WR-2721), a phosphorylated aminothiol pro-drug, is a selective cytoprotective agent in normal tissue against the toxicities associated with chemotherapy and irradiation. Fotemustine is a cancer chemotherapeutic agent that belongs to an extremely active class of alkylating compounds. Amifostine was tested for antimutagenicity against fotemustine in the somatic mutation and recombination test (SMART) in Drosophila melanogaster. Third-instar larvae that were trans-heterozygous for the two genetic markers mwh and flr were treated at different concentrations (2, 4, and 8 microg/ml for fotemustine and, 1, 2, and 4 microg/ml for amifostine) of the test compounds; for the antimutagenicity study, 8 microg/ml fotemustine plus 1 and 2 microg/ml amifostine were tested. Fotemustine showed mutagenic and recombinagenic effects in both genotypes in the wing-spot test. Amifostine significantly reduced the mutagenic and recombinagenic effects of fotemustine.

Aspirin resistance after CABG.

BACKGROUND: Temporary aspirin resistance can occur during the post-CABG period. If the factors causing resistance can be identified, the incidence of early graft occlusions can also be minimized. METHODS: 25 elective CABG cases were enrolled in the study. The platelet count, mean platelet volume, the C-reactive protein level, lipid profile, blood urea nitrogen (BUN), and creatinine levels were identified one day before the operation and on the 1st, 5th and 10th postoperative days. Optical aggregometry was used for the evaluation of aspirin response. The patients were divided into two groups: those with aspirin resistance and those with no aspirin resistance. RESULTS: The rate of postoperative aspirin resistance was found to be 60 %. No significant difference was found when the preoperative and operative data of the two groups were compared. It was found that the rapid changes observed in the postoperative platelet counts and the C-reactive protein levels were similar. CONCLUSION: Aspirin resistance is encountered during the early postoperative period in the majority of patients undergoing CABG. None of the factors studied were found to be causative for resistance formation. Further studies are required to clarify this entity.

Supracoronary myotomy for myocardial bridges in the setting of hypertrophic cardiomyopathy: off-pump experience.

Myocardial bridges (MB) are rarely observed but well known pathology of the major epicardial coronary arteries which are embedded in the overlying myocardial tissue. It is most frequently found in young patients with hypertrophic cardiomyopathy (HCM). Myocardial bridges are associated with myocardial ischemia and infarction, cardiac arrhythmias and sudden death. The present case series report the outcomes of three symptomatic patients with hypertrophic cardiomyopathy who underwent myocardial muscle debridges. They were operated using beating heart technique without cardiopulmonary bypass. The authors conclude that off-pump supracoronary muscle myotomy is a feasible treatment modality in the young age group with non-obstructive hypertrophic cardiomyopathy.

Meanings of epilepsy in its sociocultural context and implications for stigma: findings from ethnographic studies in local communities in China and Vietnam.

We investigated beliefs about the causes, course, and treatment of epilepsy and its impact on quality of life (QOL) in key target groups, using "mini-ethnographies" involving 141 in-depth interviews and 12 focus groups in China, and 84 in-depth interviews and 16 focus groups in Vietnam. Data were analyzed thematically, using a qualitative data analysis package. In both countries, beliefs about causes and triggers of epilepsy and seizures were a complex interweaving of Western, traditional, and folk medicine concepts. Epilepsy was understood to be chronic, not curable, but controllable, and was seen as enormously socially disruptive, with wide-ranging impact on QOL. Our findings suggest a more "embodied" and benign set of theories about epilepsy than in some other cultural contexts; nonetheless, people with epilepsy are still seen as having low social value and face social rejection. By exploring meanings attached to epilepsy in these two cultural contexts, we have clarified reasons behind previously documented negative attitudes and foci for future intervention studies.

Radiation-induced coronary artery disease.

Radiation-induced heart disease must be considered in any patient with cardiac symptomatology who had prior mediastinal irradiation. Radiation can affect all the structures in the heart, including the pericardium, the myocardium, the valves and the conduction system. In addition to these pathologies, coronary artery disease following mediastinal radiotherapy is the most actual cardiac pathology as it may cause cardiac emergencies requiring interventional cardiological or surgical interventions. Case A 36-year-old man was admitted to the clinic with unstable angina pectoris of one month duration. The patient had no coronary artery disease risk factor. The history of the patient revealed that he had mediastinal radiotherapy due to Hodgkin's disease at 10-year of age. Coronary arteriography showed total occlusion of the left anterior descending artery and 70% stenosis of the proximal right coronary artery. Both arteries are dilated with placement of two stents. Control coronary arteriography at the end of the first year showed patency of both stents and the patient is free of symptoms. Previous radiotherapy to the mediastinum should be considered as a risk factor for the development of premature coronary artery disease. Percutaneous transluminal coronary angioplasty with stent placement or surgical revascularization are the preferred methods of treatment. Preoperative assessment of internal thoracic arteries should be considered prior to surgery. As the radiation therapy is currently the standard treatment for a number of mediastinal malignancies, routine screening of these patients and optimal cardiac prevention during radiotherapy are the only ways to minimize the incidence of radiation-induced heart disease.

Evaluation of undergraduate training on tuberculosis at Istanbul Medical School.

SETTING: Undergraduate training on tuberculosis at Istanbul Medical School. OBJECTIVE: To assess whether tuberculosis-related questions asked in chest medicine examinations comply with the World Health Organization's (WHO) learning objectives for tuberculosis training, and to investigate students' skills in interpreting radiology and smears with respect to tuberculosis. DESIGN: Tuberculosis questions set for 4th year medical students (n = 838) were compared with WHO objectives (n = 23): 122 students were each asked to interpret 10 chest X-rays which had been read by three experts as 'typical tuberculosis lesions', 'normal' or 'non-tuberculosis lesions'; 114 students were also each given five smears which had been interpreted by an expert as 'negative' or 'positive' with respect to acid-fast-bacilli (AFB), and were asked to interpret them. RESULTS: Questions covered only nine of the WHO objectives. Among 117 types of questions, 91 (77.8%) were about clinical-radiological findings, treatment and drugs; 334 (65.1%) of 513 X-rays with typical tuberculosis lesions, 77 (21.1%) of 364 normal X-rays and 87 (25.4%) of 343 X-rays with non-tuberculosis lesions were identified as tuberculosis (kappa 0.45). Of 369 AFB-positive smears, 149 (40.4%) were evaluated as false negative, and of 185 AFB-negative smears, 48 (25.9%) were evaluated as false positive (kappa 0.49). CONCLUSION: Examination questions set on tuberculosis at Istanbul Medical School do not adequately reflect WHO learning objectives. Students' skills in interpreting radiology and smears suggest that their practical training on tuberculosis is insufficient.

Investigation of the genotoxic effect in bone marrow of Swiss albino mice exposed long-term to pyrimethamine.

In the present study, we investigated the genotoxic effect of pyrimethamine, which is a drug used in the therapy of toxoplasmosis and malaria, in bone marrow cells of Swiss albino mice exposed to three doses (1, 4, 8 mg/kg) of this agent for eight months orally in vivo. We used a chromosome analysis and micronucleus test for evaluation of genotoxic effect. While a statistically significant change was not determined in numerical chromosome abnormalities, structural chromosome aberrations and micronuclei were increased in a dose-dependent manner by cytogenetic and statistical evaluations.

Effects of Taxol plus radiation on the apoptotic and mitotic indices of mouse intestinal crypt cells.

PURPOSE: In this study we investigated the effect of Taxol, radiation, or Taxol plus radiation on highly proliferative normal tissue--the intestinal crypt cells of Swiss albino mice. MATERIALS AND METHODS: Swiss-albino mice, 3-4 months old, were used in this study. Taxol was administered by bolus intravenously through the tail vein. Radiation was given using a linear accelerator. There were four treatment categories, which comprised a total of 34 groups. Each group consisted of five animals. The first category was a control category which comprised one group (n = 5). The second treatment category was Taxol alone which comprised three groups (n = 15). The third treatment category was radiation alone which comprised three groups (n = 15). The fourth treatment category was Taxol plus radiation which comprised 27 groups (n = 135). Mice were killed 24 h after Taxol or radiation or combined administration using ether anesthesia. Using a light microscope, apoptotic and mitotic indices were counted on jejunal crypt cells of mice that were stained with hematoxylin-eosin. Differences between groups were statistically evaluated with Student's t-test. RESULTS: Taxol caused a dose-dependent increase in apoptosis (P = 0.045) and decreased the mitotic index (P = 0.006) at high doses. Similarly, radiation caused a dose-dependent increase in apoptosis (P = 0.046) and decreased the mitotic index (P = 0.299) at higher radiation doses. Compared to radiation alone, Taxol caused a significant induction of apoptosis (P = 0.010). In combination, no significant radiosensitizing effect of Taxol was observed (enhancement ratio < 1), when compared to radiation alone. However, an increase in apoptosis was observed after 24 h of Taxol exposure when compared to 12 or 48 h of Taxol exposure (P = 0.0001 and P = 0.0001). CONCLUSION: These findings suggest that Taxol did not cause a radiosensitizing effect in intestinal crypt cells. However, a 24-hour pretreatment of Taxol exposure followed by radiation caused significant induction of apoptosis and reduction of the mitotic index when compared to other Taxol timing sequences. Thus, the lack of a radiosensitizing effect of Taxol in these proliferative cells may be due to enhanced mitotic death rather than apoptotic death.

In vivo dominant lethal effect of pyrimethamine in male mouse germ cells.

Pyrimethamine is used for treatment of malaria and toxoplasmosis. The embryotoxicity and clastogenicity of pyrimethamine is known and our aim was to investigate its dominant lethal effect in vivo. For this purpose, we used three groups of Swiss-albino male mice and a control group. We injected males with doses of 16, 32 or 64 mg/kg pyrimethamine and housed them with 10 females/male for each mating interval. Females were sacrificed and their uteri were evaluated for dominant lethality. As a result of this study we found that pyrimethamine induced dominant lethal mutations in the third, fourth and sixth weeks at the 64 mg/kg dose level, without the effect being dose-dependent. We conclude that pyrimethamine is a suspected germ cell mutagen.

The cytogenetic effects of pyrimethamine on male mouse germ cells.

Pyrimethamine is an inhibitor of dihydrofolate reductase and is used in the treatment of malaria and toxoplasmosis. We examined the cytogenetic effects of this drug. Adult male mice were given doses of 20, 40, 80, and 120 mg/kg pyrimethamine intraperitoneally. Animals were killed by cervical dislocation on the 3rd, 6th, 9th, and 12th day after treatment, and the primary spermatocytes were harvested from their testes. These cells were analyzed for gaps, breaks, acentric fragments, and exchanges, as well as for numerical aberrations such as univalency. A dose-related increase in chromosomal aberrations was found in the pyrimethamine group compared with the control group. We suspect that pyrimethamine is a possible clastogen that may affect human germ cells.