Sinonasal undifferentiated carcinoma. An aggressive neoplasm derived from schneiderian epithelium and distinct from olfactory neuroblastoma

Eight cases of a highly aggressive undifferentiated carcinoma of the nasal cavity and paranasal sinuses are described. The patients, who ranged in age from 30-77 years, had multiple sinonasal symptoms, and each had involvement of the nasal cavity, maxillary antrum, and ethmoid sinus. Six tumors extended into the orbital bones, and five penetrated the cranial cavity. Five patients died of disease from 1 to 41 months after diagnosis (median: 4 months), and three are alive with tumor less than 1 year following diagnosis. Microscopically, the neoplasms formed nests, trabeculae, and sheets containing medium-sized cells with small to moderate amounts of eosinophilic cytoplasm. A high mitotic rate, tumor necrosis, and prominent vascular permeation were characteristic. Seven neoplasms were immunoreactive for cytokeratin, five for epithelial membrane antigen, and four for neuron-specific enolase. Ultrastructurally, occasional small desmosomes and rare membrane-bound, dense-core granules were observed. Sinonasal undifferentiated carcinoma is a distinctive clinicopathologic entity that must be distinguished from other, less aggressive sinonasal neoplasms.     

Distinctive immunoglobulin E anti-house dust allergen-binding specificities in a tropical Australian Aboriginal community

BACKGROUND: There is evidence that the specificity of the IgE binding in allergy tests can vary for different populations. OBJECTIVE: We aimed to examine the allergenic specificity of IgE binding in sera from house dust mite (HDM)-atopic subjects in a tropical Australian Aboriginal community. METHODS: Sera shown to contain IgE antibodies to an HDM extract of Dermatophagoides pteronyssinus were examined for IgE binding to a panel of nine purified HDM allergens from this mite species by quantitative microtitre assays. IgG antibody binding (IgG1 and IgG4) was also measured. RESULTS: The IgE-binding activity in the sera from the Aboriginal community was not directed to the expected major groups 1 and 2 HDM allergens but instead to the group 4 amylase allergen. There was also little IgE binding to the potentially cross-reactive tropomyosin (Der p 10) or arginine kinase (Der p 20) allergens. The IgG4 antibody was rarely detected and limited to the Der p 4 allergen. IgG1 antibody binding was frequently measured to all the allergens regardless of an individual's atopic status, whereas in urban communities it is restricted to the major allergens and to atopic subjects. CONCLUSION: The high IgE anti-HDM response of Australian Aboriginals predominantly bound Der p 4 and not the Der p 1 and 2 allergens, showing a distinctive allergy that could affect the disease outcome and diagnosis.     

Efficacy and safety of ezetimibe coadministered with pravastatin in patients with primary hypercholesterolemia: a prospective, randomized, double-blind trial.

AIMS: To evaluate the efficacy and safety of ezetimibe 10 mg administered with pravastatin in patients with primary hypercholesterolemia. METHODS AND RESULTS: After dietary stabilization, 2-12 week screening/washout period, and 4-week, single-blind, placebo lead-in period, 538 patients with baseline LDL-C > or =3.8 to < or =6.5 mmol/l and TG < or =4.0 mmol/l were randomized to one of eight possible treatments administered daily for 12 weeks: ezetimibe 10mg; pravastatin 10, 20, or 40 mg; ezetimibe 10 mg plus pravastatin 10, 20, or 40 mg; or placebo. The primary efficacy endpoint was percent reduction in LDL-C from baseline to study endpoint for ezetimibe 10 mg plus pravastatin (pooled doses) compared to pravastatin alone (pooled doses) and ezetimibe alone. The combined use of ezetimibe and pravastatin resulted in significant incremental reductions in LDL-C and TG compared to pooled pravastatin alone (p<0.01). Coadministration therapy reduced LDL-C by 34-41%, TG by 21-23%, and increased HDL-C by 7.8-8.4%, depending on the dose of pravastatin. The combined regimen was well tolerated, with a safety profile similar to pravastatin alone and placebo. CONCLUSIONS: When coadministered with pravastatin, ezetimibe provided significant incremental reductions in LDL-C and TG and was well tolerated with a safety profile similar to pravastatin alone.     

Effect of intravenous ketanserin on the human action potential duration at fixed heart rate

Summary In this study any changes in action potential duration or Q-T interval due to acute doses of ketanserin were monitored. The effect of a bolus dose (10 or 20 mg) followed by an infusion (10 or 20 mg over 20 minutes) of ketanserin on the Q-T interval and action potential duration was studied in six patients undergoing routine cardiac catheterization. Action potential duration was measured with a silver-silver chloride electrode catheter while heart rate was kept constant by atrial pacing and reflex effects avoided by -adrenergic blockade. There were some prolongations of the action potential duration but they were not in excess of 40 msec and did not reach statistical significance (control 263±46.0 msec; bolus 269±52.1 msec; infusion 262±53.6 msec; nor were there any significant changes in Q-T interval. Thus acute intravenous doses of ketanserin, in the absence of hypokalaemia or other Q-T interval-prolonging drugs, have no consistent effect on Q-T interval or action potential duration; prolongation of the action potential, when it occurs, is small.     

The black hole effect in perimetry

Light-emitting diodes (LEDs), mounted in drilled holes in the perimeter bowl, are used as stimuli in several automated perimeters. A concern is that these "black holes" might interrupt the otherwise uniform background illumination and cause inconsistent test results. A Dicon perimeter was modified by covering some of the LEDs with diffusing plastic. One eye of 41 normal volunteers was tested repetitively within the central 5 degrees of the visual field at the same 12 locations with both covered and uncovered LED stimuli. Higher variances of multiple threshold determinations were observed, significant at the 0.0005 level, when testing was done with uncovered LEDs. On average, the black hole effect contributed 0.8 dB to short-term fluctuation. The black hole effect is probably of minor clinical importance except in exacting quantitative perimetry.     

Preparation of the internal mammary artery graft. Which is the best method?

Early reports questioned the adequacy of flow of the internal mammary artery when used routinely as a bypass graft. "Adequate" mammary artery flow is now contested only in certain situations, that is, left ventricular hypertrophy, acute myocardial infarction, and reoperations. To compare the methods of mammary pedicle graft preparations with free mammary artery flow, we studied 31 patients who had the left internal mammary artery harvested for elective coronary artery bypass grafting. Group I comprised 14 patients whose mean body surface area was 1.91 m2. Systolic, diastolic, and mean arterial blood pressures, left atrial pressure, and heart rate were recorded and stabilized during flow measurements. Free flow of the internal mammary artery was measured before any pharmacologic manipulation and ranged from 5 to 44 ml/min (mean 18 ml/min). The grafts were sprayed and wrapped in sponges soaked in diluted papaverine solution (60 mg in 40 ml normal saline) for an average of 21 minutes. Free flow ranged from 10 to 108 ml/min (mean 51 ml/min). Intraluminal papaverine of the same dilution was then injected with hydrostatic dilatation. Immediate internal mammary artery flows rose from 150 to 333 ml/min (mean 229 ml/min). Group II comprised 17 patients who had internal mammary artery takedown under the exact conditions used in group I. Mean body surface area was 1.89 m2. Mammary artery pedicles were injected with diluted papaverine throughout their lengths with size 25 needles. After an average of 19.5 minutes, free flow ranged from 28 to 132 ml/min (mean 69 ml/min). Intraluminal diluted papaverine was then administered as in group I, and flows increased from 144 to 280 ml/min (mean 198 ml/min). The distal internal mammary arteries in both groups were 1.75 to 2.5 mm in internal diameter at the site of arteriotomy for flow measurement. This study shows that all mammary arteries are in spasm immediately after harvest and that flow is inadequate before any pharmacologic intervention. Although extraluminal vasodilators will increase free mammary artery flow, intraluminal papaverine followed by hydrostatic dilatation raises free flow to maximal capacity. Subsequent graft spasm has not been observed.(ABSTRACT TRUNCATED AT 400 WORDS)     

Sporadic medullary carcinoma of the colon: a clinicopathologic comparison with nonhereditary poorly differentiated enteric-type adenocarcinoma and neuroendocrine colorectal carcinoma

We studied 68 sporadic colorectal carcinomas (CRCs) with medullary features (MCRCs) and compared them with 35 poorly differentiated purely "enteric" CRCs (ECRCs) and 15 purely neuroendocrine carcinomas (NECs) of grades II and III, all in patients lacking a family history of CRC. Potential clinicopathologic differences between the study groups were assessed. MCRCs were significantly more common in the ascending colon than were ECRCs, but there was no significant dissimilarity to NECs. ECRCs occurred more often in the rectosigmoid than MCRCs or NECs. MCRCs arose in older patients, and a marked sex difference also was noted. Despite an infiltrative growth pattern, MCRC was less likely than ECRC to manifest with stage III or IV disease, but there was no stage-related difference from NECs. Although the histologic images of MCRCs were evocative of neuroendocrine differentiation, chromogranin positivity and synaptophysin reactivity in that group did not differ meaningfully from that of ECRCs but was dissimilar to the 100% labeling of NECs. p53 immunolabeling was similar in the 3 tumor groups. Follow-up data in the study cases showed that 5-year mortality was 40% (27/68) for MCRC, 59% (19/32) for ECRC, and 93% (14/15) for NEC. Medullary CRC seems to be a distinct clinicopathologic variant of CRC, which does not have a neuroendocrine lineage. The biologic behavior of MCRC was better than that of ECRC or NEC.