Relationship between radiation induced dicentric chromosome aberrations and micronucleus formation in human lymphocytes

Chromosome damage measured by the chromosome aberration technique is a reliable method to assess the radiation dose absorbed by cells. However, this technique has some disadvantages. Scoring is difficult and requires skill and experience which of these lead low number of cell counts. The micronucleus (MN) technique which also measures chromosome losses has easy scoring criteria leading high numbers of cell counts and therefore holds more statistical power. In this study, the relationship between the results of the micronucleus technique and those obtained by the chromosome aberration technique was investigated after radiation doses of 1Gy, 2Gy, 3Gy and 4Gy to peripheral blood lymphocytes of 3 healthy individuals. Increases in the chromosome damage after radiation were observed in both techniques. When the dicentric aberration frequencies that were measured in the chromosome aberration technique and the micronucleus frequencies were compared, no difference (p > 0.05) between these two independent measures of radiation damage was reported. The relationship between the micronuclei and the free acentric chromosome aberrations measured in the chromosome aberration technique was not significant as well as that between the dicentrics and micronuclei. On the basis of the relationship between the dicentric aberrations and the micronucleus frequencies, the micronucleus technique with an easy and short-term application and with an easy scoring can be used as an alternative to the chromosome aberration technique.     

Nutritional Status,Body Surface,and Low Lean Body Mass/Body Mass Index Are Related to Dose Reduction and Severe Gastrointestinal Toxicity Induced by Afatinib in Patients With Non‐Small Cell Lung Cancer

Background.

The main reason for dose reduction of afatinib is gastrointestinal toxicity (GT). In a phase II study, we analyzed anthropometrical, nutritional, and biochemical factors associated with GT induced by afatinib.

Materials and Methods.

Patients diagnosed with non-small cell lung cancer who progressed to prior chemotherapy received 40 mg of afatinib. Malnutrition was determined by Subjective Global Assessment, and lean body mass (LBM) was determined by computed tomography scan analysis using a pre-established Hounsfield unit threshold. Toxicity was obtained during four cycles by Common Terminology Criteria for Adverse Events.

Results.

Eighty-four patients were enrolled. Afatinib was administered as the second, third, and fourth line of treatment in 54.8%, 38.1%, and 7.12% of patients, respectively. Severe diarrhea, mucositis, and overall severe GT were present in 38.9%, 28.8%, and 57.5%, respectively. Of the patients, 50% developed dose-limiting toxicity (DLT). Patients with malnutrition have higher risk for severe GT. Patients with lower LBM and body mass index developed more DLT (71.4% vs. 18.8%).

Conclusion.

Malnutrition is associated with a higher risk of severe GT induced by afatinib. Determination of nutritional status and body composition are helpful in identifying patients at higher risk of severe GT and could allow initiating treatment with lower doses according to tolerance.

Implications for Practice:

Body composition analysis, specifically lean body mass quantification, and nutritional status assessment are significant clinical variables to take into account when assessing oncological patients. This study on patients with non-small cell lung cancer treated with afatinib showed the important impact that malnutrition and low lean body mass have on the risk for developing dose-limiting toxicity and severe gastrointestinal toxicity. Still more research needs to be done to explore dose adjustment according to lean body mass, especially in drugs that are given at fixed doses, such as afatinib. However, this study presents evidence for the clinical oncologist to have a closer follow-up with malnourished patients and even to consider a lower starting dose until therapeutic dose is achieved.     

The biochemical and histopathological effects of ursodeoxycholic acid and metronidazole on total parenteral nutrition-associated hepatic dysfunction: an experimental study

BACKGROUND/AIMS: Total parenteral nutrition causes many complications such as cholestasis. Ursodeoxycholic acid is used for the treatment of several cholestatic problems. Metronidazole was investigated before for preventing some components of total parenteral nutrition-associated hepatic dysfunction. This study was designed to investigate the effects of ursodeoxycholic acid alone and ursodeoxycholic acid + metronidazole combination on total parenteral nutrition-associated cholestasis. METHODOLOGY: Eighteen rabbits were divided into three groups as follows: group A received a standard formula of total parenteral nutrition only, group B received total parenteral nutrition + ursodeoxycholic acid (3 mg/kg/day), and group C were given total parenteral nutrition + ursodeoxycholic acid + metronidazole (25 mg/kg/day) for eight days, respectively. Several parameters of liver function tests were compared among these groups. These were transaminases, alkaline phosphatase, total bilirubin, total cholesterol, triglycerides, and serum bile acids. Liver histology was detected in each group at the end of the experiment. RESULTS: In group A, total parenteral nutrition administration resulted in remarkably higher serum values of transaminases, alkaline phosphatase, total cholesterol, total bilirubin, triglycerides, and free bile acids whereas ursodeoxycholic acid administration showed important improvements in the serum values of these parameters in group B animals. The metronidazole group showed nearer or similar laboratory values with group B, but significant differences appeared in bilirubin values (P < 0.05) among these groups. Liver histology presented marked differences between group A and group B. Steatosis formed the main component of liver histology in 4 animals out of 6 in group A. Contrary to this, all of the specimens showed normal liver structure except one in group B. In the third group we did not see better morphology than in group B. CONCLUSIONS: These results suggested that oral ursodeoxycholic acid therapy during total parenteral nutrition reduces bilirubin levels and improves the other indicators of cholestasis and helps prevent disturbances of liver histology. When it is combined with metronidazole a significant decrease in bilirubin levels has been gained. With the help of ursodeoxycholic acid we can provide enterohepatic circulation of bile acids and regulate lipid metabolism. Metronidazole can be an antibiotic of choice during total parenteral nutrition when needed.     

Behavioral changes in rats fed a diet containing 2,4-dichlorophenoxyacetic butyl ester

Oral administration of 2,4-dichlorophenoxyacetic butyl ester (2,4-Dbe) at a dose of 69 mg/kg/day to nulliparous females had no deleterious effects on either open field (OF) and rotarod performance. By contrast, dams treated with 2,4-Dbe during pregnancy exhibited impairments of OF activity, rotarod performance and improved active avoidance learning (AAL) retention. Administration of 2,4-Dbe to 90-day-old intact male rats depressed spontaneous OF activity, acquisition of conditioned avoidance responses (CARs) and rotarod endurance, but improved AAL performance. Castration itself impaired performance in the rotarod test, and improved AAL, but did not alter OF activity significantly. The effects of castration were reversed by exogenous testosterone. In gonadectomized rats, 2,4-Dbe prevented the reversal of the effect of testosterone on the influence of castration on behavior if given concomitantly with the testosterone. However, when the 2,4-Dbe treatment started seven days after testosterone, the 2,4-Dbe effects on OF, rotarod and AAL behaviors were reinstated. Thus, testosterone appears to be important for causing the toxic effects of 2,4-Dbe in rats.     

The MANIAPURE Program-Lessons Learned from a Rural Experience: Two Decades Delivering Primary Healthcare Through Telemedicine

Abstract Objective: Latin American healthcare has a common characteristic in the way countries provide assistance to the majority of their population, often represented by limitations in investment and most frequently by assigning funds to the wrong sectors of the system, which will never reach the neediest segments of the society. We want to share some lessons learned in nearly two decades serving the poorest segments of the society, despite limited funding, through the use of communication and information technologies. Materials and Methods: The data analyzed come from the accumulated experience in a remote rural center in southern Venezuela (La Milagrosa Health Center in Maniapure, Bolivar State) and further experience in over 20 similar rural clinics replicated from that case. The methodology has been a retrospective evaluation of results with a constantly maturing and dynamic practice at three levels of care: (1) remote (basic clinic), (2) a virtual triage center, and (3) a specialty level. Results: We analyzed qualitative results on access to specialty care of previously excluded communities (populations) and the significant cost reduction (social and financial) by avoiding unnecessary travel for the majority of consulting patients. In cases needing subspecialty care that require travel, the effectiveness of such activity is optimized in time and service. Conclusions: Communication and information technologies can provide significant savings to society and improve healthcare with the use of common and relatively inexpensive consumer-level devices if used in a basic, coordinated system of services with adequate training and follow-up.     

Sonographic anatomy of the neck: The suprahyoid region

The suprahyoid region extends from the base of the skull to the hyoid bone and includes the pharyngeal, parapharyngeal, parotid, carotid, masticator, retropharyngeal, and perivertebral spaces, as well as the oral cavity. The areas that can be explored by ultrasound include the parotid, carotid, and masticator spaces; the oral cavity; the submandibular and sublingual spaces; the floor of the mouth; and the root of the tongue. The parotid space contains the parotid gland and the excretory duct of Steno, the facial nerve, the external carotid artery, the retromandibular vein, and the intraparotid lymph nodes. The carotid space in the suprahyoid region of the neck contains the internal carotid artery, the internal jugular vein, cranial nerves IX to XII, and the sympathetic plexus. Only some parts of the masticator space can be explored sonographically: these include the masseter muscle, the zygomatic arch and the outer cortex of the ramus of the mandible, and the suprazygomatic portion of the temporalis muscle. The submandibular space houses the submandibular gland, the submental and submandibular lymph nodes, and the anterior belly of digastric muscle. The facial artery and vein and the lower loop of the hypoglossal nerve all pass through the submandibular space. The sublingual space includes the sublingual gland, the deep portion of the submandibular gland and its main excretory duct, the hypoglossal nerve (cranial nerve XII), the lingual nerve (branch of the mandibular branch of trigeminal), and the glossopharyngeal nerve (IX cranial nerve), and the lingual artery and vein. The mylohyoid muscle forms the floor of the mouth. The deepest portion of the oral tongue, the root, consists of the genioglossus and geniohyoid muscles and includes the septum of the tongue. In this article we present the ultrasound features of the structures located in the suprahyoid region of the neck.     

Malignant peritoneal mesothelioma presented as peritoneal adenocarcinoma or primary ovarian cancer: case series and review of the clinical and immunohistochemical features

Diffuse peritoneal malignant mesothelioma is a rare, progressive, and ultimately fatal disease and it can present as primary peritoneal carcinoma or ovarian cancer. Differential diagnosis is important to establish appropriate management. In this article the clinical presentation, immunuhistochemical and histopathological features of 8 diffuse peritoneal malignant mesothelioma cases presented as peritoneal carcinoma or ovarian cancer are evaluated. According to findings of all reported cases, we concluded that clinical distinction of malignant mesothelioma from ovarian cancer or peritoneal adenocarcinoma is very difficult. Differential diagnosis is reliably achieved by immune profile of the tumors with a systematic approach of both positive and negative mesothelioma markers.     

Neoadjuvant chemotherapy equalizes the optimal cytoreduction rate to primary surgery without improving survival in advanced ovarian cancer

Purpose(s)

To evaluate results of neoadjuvant chemotherapy (NACT) following debulking surgery in patients with extensive metastatic disease and/or poor medical performance

Method(s)

Advanced stage epithelial ovarian cancer patients were treated with either NACT followed by debulking surgery or primary surgery followed by adjuvant chemotherapy after assessment of the extent of disease by laparoscopy or laparotomy.

Results

Out of 297, 223 patients were in the primary surgery group, whereas 74 of them met NACT criteria. Optimal cytoreduction rates were 63.2 % in primary surgery group and 60.8 % in NACT group, respectively (p: 0.709). In the primary surgery group, the overall survival was significantly higher (p: 0.002). Mean patient age was more advanced (p: 0.014) and the performance status of patients was poorer (p < 0.001) in NACT group. Only patient group (primary surgery or neoadjuvant chemotherapy) (p: 0.001) retained significance as predictors of survival in multivariate analyses.

Conclusion(s)

Improved rate of optimal cytoreduction with NACT in advanced ovarian cancer patients does not prolong survival. The extent of disease at diagnosis is the primary determinant of survival. Randomizing patients with equally extensive disease and performance status to either NACT or primary debulking surgery in a future study will better clarify benefits attributed to NACT.     

CT findings of hydatid cyst with unusual location: infratemporal fossa

Hydatid disease has a high incidence in the countries of the temperate zones such as Turkey. Only few cases in the head and neck region have been reported in the literature. Our case, an unusual localization of hydatidosis, i. e. hydatid disease of the infratemporal fossa of a 9-year-old male patient suffering from a swelling of the left maxillary region which was diagnosed by CT, is presented. The lesion visualized on CT images was compressing the neighbouring structures. The possible diagnosis was made based on the images obtained from CT examination. Received 17 November 1997; Revision received 28 January 1998; Accepted 2 March 1998