A novel porcine model for chemically inducible Crohn's-like reaction.

BACKGROUND: New animal models provide insights into the pathogenesis of different types of inflammatory bowel disease as well as novel pathways for new therapeutic options. However, the scarcity of large animal models hinders the research and development of new surgical procedures and technological devices in inflammatory bowel disease surgery. Common small animal inducible models involve chemical agents that result in the development of acute intestinal inflammation. OBJECTIVES: To assess a novel method for the induction of Crohn's-like colitis using intramural injection of sclerosants in a porcine model. METHODS: Seven domestic pigs underwent several experimental protocols to assess the efficacy of intramural colonic injections of two different compounds (lauromacrogol, and phenol in almond oil).Twenty-five different large bowel segments were treated with intramural injections of the compounds. The animals were followed for 6 weeks, and treated colonic segments were resected for histopathological examination. RESULTS: Intramural injection of lauromacrogol resulted in non-specific, mild reactive foreign body changes only. Injection of various dosages of 5% phenol in almond oil caused a range of histopathological changes varying from focal fibrosis to Crohn's-like reactions com rising acute and chronic infiltrates, mucosal ulceration and focal necrosis with enteric and lymphoid non-caseating granulomas. CONCLUSIONS: Intramural colonic phenol in almond oil injection in pigs induces inflammatory reactions that histologically resemble Crohn's disease in humans.

Serum DNA methylation for monitoring response to neoadjuvant chemotherapy in breast cancer patients.

Patients with large or nonoperable breast cancers often receive neoadjuvant chemotherapy to facilitate full resection of the tumor and enable conservation of the breast. However, currently available methods for evaluation of response during therapy are limited and the actual effect of the treatment is only recognized at surgery upon completion of chemotherapy. Timely assessment of response could allow individual tailoring of the treatment and save noneffective drugs and unnecessary toxicity. Here, we suggest that tumor derived DNA methylation in the serum may reflect changes in tumor burden and allow early recognition of responders versus nonresponders. In this pilot study, we collected 7 consecutive serum samples from 52 patients with locally advanced breast cancer during neoadjuvant chemotherapy. We selected RASSF1, which was methylated in more than 80% of the tumors, for serum analysis. Using the "methylation sensitive PCR and high resolution melting," we detected RASSF1 methylation in the serum of 21 patients prior to therapy. In four patients who achieved complete pathological response, RASSF1 methylation in the serum became undetectable early during therapy. In contrast, in 17 patients that had partial or minimal pathological response, serum RASSF1 methylation persisted longer or throughout the treatment (complete versus partial response p = 0.02). These findings support further development of this assay for monitoring response during neoadjuvant therapy.

[The prevalence of physical evidence in the anogenital area in sexual assault cases of children in Israel].

INTRODUCTION: Sexual abuse includes obscenity, rape and sodomy. Forensic medical examinations routinely include the genital area, anus and the body of the victims for signs of recent or old injury. OBJECTIVES: To evaluate the incidence of physical evidence in forensic sexual abuse cases and to compare the Israeli findings to data from other countries, including the USA. METHODS: The study was conducted during one calendar year in Israel and included 95 children from infancy to 16 years of age, of whom 83% were females. Examination results were defined by the presence of physical injury or its absence. These findings were classified by their location in the anogenital area or other body areas and findings in the anogenital area were further classified by their likelihood to have been caused by a sexual assault. The results of the examination were related to parameters such as age and sex of the participants, length of time since the last assault, and the degree of proximity between the suspected assailant and the victim. RESULTS: Evidence of physical abuse was found in 41 patients, in 37 (39%) of these cases physical abuse was detected in the anogenital area. In all these cases of anogenital abuse, 11 (12%) showed clear evidence of sexual assault and five of them had recent signs of injury; 80% of the recent injuries in the anogenital area were identified in patients within the first 24 hours after the assault. CONCLUSIONS: The prevalence of clear evidence of sexual assault in the U.S. ranges from 3-23%, in Italy 9.5%, in Thailand 32% and in Denmark 40%. In Israel, as elsewhere in the world, few cases of sexual assault in children will have clear evidence of a sexual nature. A lack of physical evidence does not rule out sexual assault, therefore, finding physical evidence during an examination is the exception rather than rule. Questioning the victim and investigating the circumstances of the case are crucial elements in all instances of presumed sexual assault on children.