Residents' management of the symptoms associated with terminal cancer

The principal aim of palliative care is to bring symptomatic relief to patients with progressive disease. Residents graduating from a university general surgery training program should be competent to manage common symptoms associated with advanced cancer. This study used performance-based testing to evaluate the skills of resident physicians in managing common symptoms of a patient with advanced cancer. Thirty-three resident physicians (PGY 1 to 6) were presented with four clinical symptoms of a patient with advanced cancer: (1) nausea and vomiting associated with regular morphine use; (2) lack of appetite in the last weeks of life of a terminally ill patient; (3) constipation associated with codeine analgesia; and (4) dyspnea associated with diffuse lung metastases. The management plan for the symptom problems was evaluated by using a predefined checklist. A significant number of residents showed deficits in the management of common symptoms of advanced cancer. Scheduled dosing of antiemetics was infrequently prescribed for opioid-related nausea and vomiting. Most physicians inappropriately managed lack of appetite by using forced feeding. Opioids were infrequently used in the management of terminal dyspnea. The absence of difference in scores between junior and senior residents suggests that adequate management of the symptoms of terminal cancer is not being effectively taught in postgraduate training programs.     

Elastin and collagen accumulation in rabbit ascending aorta and pulmonary trunk during postnatal growth. Correlation of cellular synthetic response with medial tension

Absolute and relative quantities of elastin, collagen, and DNA in anatomically defined segments of rabbit ascending aorta (AA) and pulmonary trunk (PT) were compared at intervals from birth to 2 months of age. Identical in size, weight, and composition at birth, the vessels maintained similar lengths and diameters at each age but diverged markedly in weight and scleroprotein content after 1 week. By 2 months, 3 times as much elastin and 1.7 times as much collagen had accumulated in the AA as compared to the PT. By contrast, the increase in total DNA content was the same for both segments. Differences in total fibrous protein accumulation, total elastin accumulation, and elastin content relative to DNA paralleled differences in estimated total medial tangential tension. Proportions of elastin and collagen relative to dry weight increased markedly only between 4 and 2 weeks of age and not thereafter despite continuing rapid growth, steadily increasing medial tension, and increasing total scleroprotein content. Thus, medial cells were capable of adapting their quantitative scleroprotein synthetic response to differences in medial tension throughout growth but established a fixed qualitative response within 2 weeks.     

Cyclophosphamide and low-dose prednisone therapy in patients with systemic sclerosis (scleroderma) with interstitial lung disease

Fourteen patients with systemic sclerosis (SSc, scleroderma) and interstitial lung disease were treated with oral cyclophosphamide (1-2 mg/kg/day) and low dose prednisone (< 10 mg/day). There was a significant improvement in FVC after 6 months compared to entry values (2.21 +/- 0.19 l vs. 2.03 +/- 0.15 l, p < 0.02). Improvement was maintained at 12 months (2.27 +/- 0.27 l, p < 0.05) and 18-24 months (2.60 +/- 0.28 l, p < 0.001). In 12 cases followed for 18-24 months, FVC was stable or improved. No significant improvement or decline was noted for the DLCO. Side effects included cytopenia (2), infection (1), and hemorrhagic cystitis (2), and one possible related malignancy. A controlled prospective trial of cyclophosphamide is warranted in patients with SSc and active interstitial lung disease.     

Cloning and functional characterisation of two novel nicotinic acetylcholine receptor alpha subunits from the insect pest Myzus persicae

Nicotinic acetylcholine receptors play a major role in excitatory neurotransmission in insect CNSs and constitute an important target for insecticides. Here, we report the isolation and functional characterisation of two cDNAs encoding nicotinic acetylcholine receptor alpha subunits from a major insect pest, the peach-potato aphid Myzus persicae. These two subunits, termed Mp alpha1 and Mp alpha2, are respective structural homologues of the Drosophila D alpha2/Schistocerca gregaria alphaL1 alpha-subunit pair and the Drosophila ALS alpha subunit. Xenopus oocyte expression confirmed that each Myzus subunit can form functional acetylcholine- or nicotine-gated channels. However, some electrophysiological and pharmacological properties of the Myzus subunits were distinct from those encoded by the corresponding Drosophila subunits. Coexpression of the Myzus subunits with the chick beta2 subunit revealed other differences from the Drosophila system, as only very limited potentiation of agonist-induced currents was observed with Mp alpha2 and none with Mp alpha1. Available data therefore indicate that structurally homologous insect nicotinic acetylcholine receptor alpha subunits from different species can exhibit distinctive physiological and pharmacological characteristics.     

Insight into the mechanism(s) through which TNF promotes the generation of T cell-mediated antitumor cytotoxicity by tumor bearer splenic cells

We have shown previously that addition of TNF to stimulation cultures of MOPC-315 tumor bearer splenic cell suspensions containing metastatic tumor cells capable of secreting TGF-beta greatly enhances the generation of anti-MOPC-315 lytic activity by their CD8+ T cells. The current studies were undertaken to gain some insight into the mechanism(s) through which TNF potentiates the in vitro generation of anti-MOPC-315 cytotoxicity by such tumor bearer splenic cells. Here we show that TNF is capable of 1) preventing completely the inhibitory activity of TGF-beta for CTL generation when both cytokines are added at the time of initiation of a 5-day stimulation culture and 2) reversing at least part of the inhibitory activity of TGF-beta when TNF is added as late as 3 days after TGF-beta addition. The costimulatory molecule B7-2 is shown here to be important for the realization of the potentiating activity of TNF for CTL generation by tumor bearer splenic cells. However, despite the importance of the B7-2 molecule, TNF does not mediate its immunopotentiating activity for CTL generation through up-regulation in IL-2 production. In addition, we show here that GM-CSF, but not IL-12, is important for the potentiating effect of TNF for CTL generation by tumor bearer splenic cells. Taken together, these studies identify several factors that are important for the realization of the potentiating effect of TNF for the in vitro generation of antitumor cytotoxicity by tumor-infiltrated splenic cells. It is not known at present, however, whether these factors utilize distinct and/or overlapping mechanisms in realizing the TNF effect.     

Prolonged survival in a patient with sinonasal teratocarcinosarcoma with cranial extension. Case report

Sinonasal teratocarcinosarcoma is a rare malignant neoplasm characterized by the combined histological features of carcinosarcoma and teratoma. The primary symptoms of this tumor are usually nasal obstruction and epistaxis, and a nasal cavity mass is the most common clinical finding. The authors describe an exceptionally rare case in which the patient presented with massive intracranial extension and exhibited confusion as an initial symptom. He subsequently underwent combined radical surgery and radiation therapy and has remained free of disease for 31 months. The surgical approach to the lesion, histological features, and clinical course are detailed.