The frequency of concha bullosa, paradoxical middle turbinate, and septal deviation on coronal computed tomographic scans evaluating sinus disease is known, but the incidence in normal subjects is unknown. We compared 100 consecutive scans performed for evaluation of sinus disease with 82 consecutive scans performed for evaluation of orbital pathology. Patients with sinus disease had significantly more frequent findings of disease in the osteomeatal complex and all sinuses. Concha bullosa was more common in patients with sinus disease (p less than 0.05), as was septal deviation (p less than 0.01). Paradoxical turbinate was equally common. Concha bullosa was associated with anterior ethmoid disease (p less than 0.04). Septal deviation was associated with osteomeatal complex disease (p less than 0.01) and with anterior (p less than 0.04) and posterior (p less than 0.04) ethmoid disease. Paradoxical turbinate was not associated with sinus abnormalities. These data imply a possible causal relationship between concha bullosa or septal deviation and sinus disease.

To assess the role of adjuvant therapy in the treatment of osteogenic sarcoma of the head and neck, treatment and survival information from 173 patients with osteosarcoma of the head and neck was entered into a database. A meta-analysis of the data was attempted with primary emphasis on the effect of adjuvant therapy on disease outcome. The overall 5-year survival was 37%. Patients with mandibular and maxillary tumors had similar survival rates; both groups fared significantly better than patients with extragnathic tumors (P<0.001). Treatment with surgery alone was associated with significantly longer survival rates (P<0.03) than surgery with adjuvant therapy. In the majority of patients reported, information about surgical margins was not available. For this reason, the differences may not adequately represent the effect of adjuvant therapy. While there have been encouraging results with adjuvant treatment protocols for long bone osteosarcoma, the ultimate role of radiation and chemotherapy in the management of osteosarcoma of the head and neck remains unproven. Nevertheless, we recommend that adjuvant therapy be considered due to the poor prognosis in osteosarcoma of the head and neck.

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Distant metastases (DMs) occurred in 83 (11.4%) of 727 retrospectively studied head and neck cancer patients. Primary tumor location and initial treatment did not influence DM development; larger primaries (P < .04) or more extensive neck disease (P < .007) more often caused DMs. Initial diagnosis to DMs averaged 11.7 months (range, 0 to 60 months), with 84% diagnosed within 24 months. With the exception of laryngeal primaries, no facet of tumor, host, or initial treatment influenced where or how rapidly DMs developed. Lung was the most common DM site (83.4%), then bone (31.1%) and liver (6.0%). Survival with DMs averaged 4.3 months (range, 1 day to 2.7 years); 86.7% died within 1 year. This report yields the following conclusions: 1. Initial tumor size and neck disease are the only predictors of DMs. 2. DMs usually occur within 2 years of the initial diagnosis. 3. Lung is the most common DM site, making chest x-ray the most effective DM screen. 4. Survival with DMs is usually less than a year.

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OpenWorm is an international collaboration with the aim of understanding how the behavior of Caenorhabditis elegans (C. elegans) emerges from its underlying physiological processes. The project has developed a modular simulation engine to create computational models of the worm. The modularity of the engine makes it possible to easily modify the model, incorporate new experimental data and test hypotheses. The modeling framework incorporates both biophysical neuronal simulations and a novel fluid-dynamics-based soft-tissue simulation for physical environment-body interactions. The project's open-science approach is aimed at overcoming the difficulties of integrative modeling within a traditional academic environment. In this article the rationale is presented for creating the OpenWorm collaboration, the tools and resources developed thus far are outlined and the unique challenges associated with the project are discussed.

Estradiol is converted to catechol estrogens via 2-and 4-hydroxylation by cytochrome P450 enzymes. 4-Hydroxyestradiol elicits biological activities distinct from estradiol, most notably an oxidant stress response induced by free radicals generated by metabolic redox cycling reactions. In this study, we have examined 2-and 4-hydroxylation of estradiol by microsomes ofhuman uterine myometrium and of associated myomata. In all eight cases studied, estradiol 4-hydroxylation by myoma has been substantially elevated relative to surrounding myometrial tissue (minimum, 2-fold; mean, 5-fold). Estradiol 2-hydroxylation in myomata occurs at much lower rates than 4-hydroxylation (ratio of 4-hydroxyestradiol/2-hydroxyestradiol, 7.9 + 1.4) and does not significantly differ from rates in surrounding myometrial tissue. Rates of myometrial 2-hydroxylation of estradiol were also not significantly different from values in patients without myomata. We have used various inhibitors to establish that 4-hydroxylation is catalyzed by a completely different cytochrome P450 than 2-hydroxylation. In myoma, at-naphthoflavone and a set of ethynyl polycyclic hydrocarbon inhibitors (5 ,uM) each inhibited 4-hydroxylation more efficiently (up to 90%o) than 2-hydroxylation (up to 40%o), indicating >10-fold differences in Kj (<0.5 ,uM vs. >5 ,uM). These activities were clearly distinguished from the selective 2-hydroxylation of estradiol in placenta by aromatase reported previously (low K., inhibition by Fadrozole hydrochloride or ICI D1033).4-Hydroxylation was also selectively inhibited relative to 2-hydroxylation by antibodies raised against cytochrome P450 IBN (rat) (53 vs. 17%). These data indicate that specific 4-hydroxylation of estradiol in human uterine tissues is catalyzed by a form(s) ofcytochrome P450 related to P450 IBi, which contribute(s) little to 2-hydroxylation. This enzyme(s) is therefore a marker for uterine myomata and may play a role in the etiology of the tumor. (E2) is the primary metabolic oxidation of this hormone in most mammalian species (1, 2). In human liver, this metabolic oxidation is catalyzed mainly by cytochrome P450 IIIA and, to a lesser extent, IA family enzymes (2, 3). Cytochrome P450 IA enzymes have also been identified as estrogen 2-hydroxylases in extrahepatic tissues and in MCF-7 human breast cancer cells (2, 4, 5). In addition, aromatase has been reported to catalyze the 2-hydroxylation of E2 in placenta (6). Aromatic hydroxylations of estrogens by these enzymes mainly result in 2-hydroxylated catechol estrogens (CE) accompanied by small amounts of 4-hydroxylated estrogens (<20% of total CE metabolites) (1, 2). Therefore, 4-hydroxyestradiol (4-OH-E2) has been considered as an unimportant by-product of 2-hydroxyestradiol (2-OH-E2) formation because rates of its formation by microsomal preparations are low relative to total CE formation (1, 2) and also because urinary concentrations of 4-hydroxylated estrogens are much lower than those of 2-hydroxylated metabolites (7,8). In contrast, in microsomes o...

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