Assessment of 3-nitro-1,2,4-triazol-5-one as a potential endocrine disrupting chemical in rats using the Hershberger and uterotrophic bioassays.

The explosive 3-nitro-1,2,4-triazol-5-one (NTO) is an insensitive formulation developed to replace high energetics that are susceptible to accidental detonation from heat, shock, and impact. Although studies have shown NTO to be nontoxic at acute exposures, recent subacute and subchronic tests have demonstrated effects on testes and subsequent sperm production in rats. This study assessed endocrine disruption as a potential mechanism for these reproductive effects via the Hershberger and uterotrophic bioassays. These assays are 2 of the US Environmental Protection Agency's tier 1 in vivo screens for the Endocrine Disruptor Screening Program that measure differences in androgen- and estrogen-sensitive tissue weights in castrated and ovariectomized rats. The gonadectomized rats were orally exposed to NTO in a corn oil vehicle at doses of 250, 500, or 1000 mg/kg body weight (bw)/d for 10 and 3 days for the Hershberger and uterotrophic assays, respectively, according to standard protocols. Male rats also received testosterone (0.2 mg/kg/d, subcutaneous) and antiandrogenic flutamide (3mg/kg/d, oral) as negative and positive controls, and females received 17 α-ethynyl estradiol (0.3 µg/d, subcutaneous) as positive controls. 3-Nitro-1,2,4-triazol-5-one caused neither a decrease in androgen-sensitive male reproductive selected tissue (seminal vesicles with fluid/without fluid, glans penis, Cowper gland, ventral prostrate, and levator ani-bulbocavernosus) weights nor a change in uterine weights. The results of this study provide no evidence to suggest that NTO acts like an estrogenic or antiandrogenic endocrine disruptor in rats at these doses.

Altered innervation of the fallopian tube in ectopic pregnancy.

Three cases of ectopic pregnancy demonstrate different patterns of abnormal innervation in the fallopian tube. In the isthmus of the fallopian tube, we observed either (1) loss of nerves in one or more muscle layers of the fallopian tube or (2) large numbers of abnormal nerve profiles in one or more layers of muscle of the fallopian tube. Each woman had a prior history of one or more surgical terminations of pregnancy at indeterminate gestational ages. A proportion of uterine and tubal nerves pass through the uterosacral ligaments to reach the endometrial-myometrial nerve plexus and terminate as the innervation to the ipsilateral fallopian tube. We propose that injuries to the uterosacral ligaments by excessive traction to the cervix, or over-vigorous curettage to the endometrial-myometrial nerve plexus may account for these neuro-immunohistochemical findings. There were no signs of chronic infection or inflammation in the fallopian tube in any of these cases.

The management of cervical lymph nodes in patients with cutaneous melanoma.

BACKGROUND: The aim of this study was to review the management of cervical lymph nodes in patients with cutaneous melanoma and to analyze factors influencing prognosis. METHODS: This was a retrospective cohort study of patients who had cervical node surgery at the Sydney Melanoma Unit from 1990 to 2004. RESULTS: Of 716 patients who met the study criteria, 339 had a sentinel node biopsy (SNB) and 396 had a neck dissection. Locoregional recurrence occurred in 27.6 % of those undergoing therapeutic neck dissection and 60 % eventually developed distant metastases. Radiotherapy was given as adjuvant treatment in 110 of the patients who had a therapeutic neck dissection (41 %), but this was not associated with improved regional control (p = .322). Multivariate analysis showed that nodal positivity (p < .001) and primary tumor ulceration (p = < .027) were the most important predictors of locoregional recurrence and that primary tumor Breslow thickness (p = .009) and node positivity (p = .046) were the most important factors predicting survival. SNB-positive patients who underwent immediate completion lymphadenectomy had a 5-year survival advantage over those who had a therapeutic neck dissection for macroscopic disease (54 % vs 47 %, p = .028). CONCLUSIONS: Nodal status was the most important factor predicting disease-free and overall survival in patients with melanoma of the head and neck. Adjuvant radiotherapy was not associated with better locoregional control in the non-randomized cohorts of patients in this study.