Chondrosarcoma of the larynx: a clinicopathologic study of 111 cases with a review of the literature

Chondrosarcomas of the larynx are rare tumors accounting for about 0.5% of all laryngeal primary tumors. A total of 111 laryngeal chondrosarcoma cases, diagnosed between 1970 and 1997, were retrieved from the Otorhinolaryngic-Head & Neck Tumor Registry of the Armed Forces Institute of Pathology. There was a 3.6:1 male/female ratio of patients 25-91 years of age (mean, 64.4 years). Patients presented most frequently with hoarseness (n = 72 patients) present for a mean of 28.2 months. The majority of tumors involved the cricoid cartilage (n = 77) with a mean size of 3.5 cm. All tumors were invasive and malignant by radiology and/or histology (into bone within the ossified laryngeal cartilages in 52 tumors). Most tumors were low-grade lesions: grade 1 (n = 51), grade 2 (n = 54); there were six grade 3 tumors. An associated benign chondroma with (n = 41 tumors) or without ischemia (n = 24 tumors) was noted. All patients had surgery and five had radiation therapy. Wide excision or voice-sparing surgery was used in 73 patients, whereas 37 patients had a laryngectomy. Recurrences occurred in 20 (18%) patients, 10 of whom underwent salvage laryngectomy. At the last follow-up, 102 patients had no evidence of disease (alive or dead, mean 11.2 years) and five patients had evidence of disease (alive, one patient, 6.5 years; dead, four patients, mean 6.4 years). The six patients with high-grade chondrosarcoma were all without disease at the last follow-up (mean, 15.1 years). There was no difference in clinical outcome based on grade (p = 0.210), location (p = 0.078), or treatment (p = 0.607) but was worse for patients with a myxoid-type chondrosarcoma (p = 0.044). Primary laryngeal chondrosarcomas are typically low- to moderate-grade lesions involving the cricoid cartilage, frequently associated with a chondroma. They usually portend an excellent overall long-term prognosis with initial conservative voice-sparing surgery.     

A winning combination: women,literacy, and participation in health care

Health information materials written at the appropriate reading level help individuals manage their own health care. In this study, we assessed the reading ability of clients and readability of the patient information materials at a rural women's health clinic. We administered a reading comprehension test to 50 subjects and tested the patient education materials using a readability formula. More than one in six women could not read all of the patient information, which could limit their understanding, and achievement of good health care. Commercially available materials can be checked readily for reading level using software installed in most computers. This software also allows clinicians who prepare their own materials for their patients to generate versions that are appropriate for different reading levels.     

Escherichia coli O157:H7 infection in cows and calves in a beef cattle herd in Alberta,Canada

Escherichia coli O157:H7 infection of cows and calves in a naturally-infected beef cattle herd in Alberta, Canada, was investigated over 2 years, encompassing two calf production cycles. In both years of the study, E. coli O157:H7 was isolated from the faeces of cows shortly after but not before parturition in late winter: 6/38 (16%) in 1996 and 13/50 (26%) in 1997. At < 1 week post-partum, 13/52 (25%) calves born in 1997 were shedding the organism. Faecal shedding of E. coli O157:H7 by cows and calves continued over the 7 weeks that they were in the calving pens, with the organism being isolated from the faeces of 2-18% of cows and 23-26% of calves during this period. Five weeks after they were moved onto a native grass pasture, all the calves and all but one cow in 1997 had ceased shedding the organism. When the calves were weaned in the fall, E. coli O157:H7 was isolated from the faeces of 0-1.5% of the calves 1 week prior to weaning and from 6-14% of the calves within 2 weeks after weaning. Parturition, calving pens and weaning appear to be important factors in maintaining E. coli O157:H7 infections in this beef cattle herd. Isolates from cows and calves during the immediate post-partum period were mostly of the same pulsed-field gel electrophoresis (PFGE) type of E. coli O157:H7. Similarly, at weaning a common PFGE type of E. coli O157:H7, which differed slightly from the post-partum PFGE type, was isolated from the calves. These typing data suggest a common source of infection for the animals as well as demonstrate clonal turnover of resident populations of this pathogen.     

Absorption, distribution, metabolism, and elimination of 8-2 fluorotelomer alcohol in the rat.

The absorption, distribution, metabolism, and elimination of [3-14C] 8-2 fluorotelomer alcohol (8-2 FTOH, C7F1514CF2CH2CH2OH) following a single oral dose at 5 and 125 mg/kg in male and female rats have been determined. Following oral dosing, the maximum concentration of 8-2 FTOH in plasma occurred by 1 h postdose and cleared rapidly with a half-life of less than 5 h. The internal dose to 8-2 FTOH, as measured by area under the concentration-time curve to infinity, was similar for male and female rats and was observed to increase in a dose-dependent fashion. The majority of the 14C 8-2 FTOH (> 70%) was excreted in feces, and 37-55% was identified as parent. Less than 4% of the administered dose was excreted in urine, which contained low concentrations of perfluorooctanoate (approximately 1% of total 14C). Metabolites identified in bile were principally composed of glucuronide and glutathione conjugates, and perfluorohexanoate was identified in excreta and plasma, demonstrating the metabolism of the parent FTOH by sequential removal of multiple CF2 groups. At 7 days postdose, 4-7% of the administered radioactivity was present in tissues, and for the majority, 14C concentrations were greater than whole blood with the highest concentration in fat, liver, thyroid, and adrenals. Distribution and excretion of a single 125-mg/kg [3-14C] 8-2 FTOH dermal dose following a 6-h exposure in rats was also determined. The majority of the dermal dose either volatilized from the skin (37%) or was removed by washing (29%). Following a 6-h dermal exposure and a 7-day collection period, excretion of total radioactivity via urine (< 0.1%) and feces (< 0.2%) was minor, and radioactivity concentrations in most tissues were below the limit of detection. Systemic availability of 8-2 FTOH following dermal exposure was negligible.     

Overexpression of vascular endothelial growth factor-A165 enhances tumor angiogenesis but not metastasis during beta-cell carcinogenesis.

The pivotal role of vascular endothelial growth factor (VEGF-A) in the regulation of angiogenesis, in particular in the onset and maintenance of tumor angiogenesis, has been demonstrated repeatedly in experimental model systems and, more recently, in clinical trials. Experimental evidence has also suggested that up-regulated expression of VEGF-A may cooperate with other genetic or epigenetic changes to induce or accelerate tumor progression to invasive and metastatic cancers. Here we report the generation of transgenic mouse lines that express human VEGF-A165 under the control of the rat insulin promoter in the beta cells of pancreatic islets of Langerhans (Rip1VEGF-A). These mice do not exhibit detectable changes in islet development, vascularization, or physiology. Intercrosses of these mice with a transgenic mouse model of pancreatic beta cell carcinogenesis (Rip1Tag2) result in an earlier onset of tumor angiogenesis and with it accelerated tumor growth and mortality. The transition from benign tumors (adenoma) to malignant tumors (carcinoma) is modestly accelerated; however, tumor metastases are not observed. Our findings indicate that in beta-cell tumorigenesis, overexpression of VEGF-A165 accelerates the onset of tumor angiogenesis and with it tumor progression but is not sufficient to induce tumor metastasis.     

Nasal obstruction: an alternative to ostiomeatal complex dysfunction in sinus disease

OBJECTIVES: Ostial patency is thought to be essential to the function of the maxillary sinus. Ostiomeatal complex dysfunction has been implicated as a major factor in the pathogenesis of sinus disease. However, recent work in our laboratory has indicated that other factors may also contribute to this process. The objective of this study was to determine the effect of nasal obstruction in maxillary sinus gas composition, independent of its effect on ostial ventilation. STUDY DESIGN: Prospective controlled animal study. METHOD: Independent models of nasal obstruction and ostial occlusion in contralateral sinuses were established. Ipsilateral models of nasal obstruction and ostial occlusion were also created. Gas samples from each of the manipulated sinuses were analyzed on a gas chromatogram and compared. RESULTS: Results revealed a dramatic and highly significant increase in antral carbon dioxide (CO2) concentrations in the sinuses ipsilateral to either an occluded ostium or an obstructed nostril, compared with the controls. These effects on CO2 concentrations were additive when ipsilateral nasal obstruction and ostial occlusion were created. Furthermore, the effect of nasal obstruction in modulation of antral CO2 levels was found to be beyond its effect on hypoventilation of the sinus and to be independent of ostial functional status. CONCLUSIONS: We have established independent models of nasal obstruction and ostial occlusion in the same animal. Our findings suggest that ostiomeatal complex dysfunction might not be the sole underlying factor in the pathogenesis of sinus disease in all individuals. Integrity of nasal airflow seems to have a significant effect on the maintenance of the aerobic antral environment, essential to the maintenance of normal sinus function. Modulation of maxillary sinus gas composition by nasal airflow, independent of ostial patency, may be explained by the possible presence of flow-sensitive receptors in the upper respiratory tract mucosa. Work to identify such receptors is currently in progress.     

Safety and efficacy of pulse and daily calcitriol in patients on CAPD: a randomized trial

Background: Calcitriol therapy is the mainstay of therapy for the treatment of secondary hyperparathyroidism. Oral administration of calcitriol is necessary in CAPD patients, but no studies have directly compared different routes of administration in this patient population. Methods: To determine if the peak serum calcitriol level (pulse therapy) is more important than the total delivered dose, we randomized CAPD patients with mild to moderate secondary hyperparathyroidism to receive either pulse (3.0 &mgr;g twice a week, n=10) or daily (0.75 &mgr;g a day, n=8) oral calcitriol in comparable weekly doses. The main comparison was the rate of decline of serum intact parathyroid hormone (PTH) levels to reach the desired end-point of 100 pg/ml. The patients were dialysed with low-calcium dialysate and received only calcium-containing phosphate binders. Results: Pharmacokinetic analysis after a single dose of 3.0 &mgr;g (pulse) vs 0.75 &mgr;g (daily) revealed 1,25(OH)2-vitamin D levels to be higher in the pulse group at 3 and 6 h, but equivalent by 12 h. The area under the curve for 1 week of daily and 1 week of pulse therapy was equal. The patients in the 2 arms had equivalent basal serum levels of PTH (pulse=562±291 vs daily=454±113 pg/ml), calcium (pulse=2.32±0.20 vs daily=2.32±0.12 mmol/l) and phosphorus (pulse=1.32±0.52 vs daily=1.35±0.26 mmol/l). The time required for the PTH to decrease to 100 pg/ml and rate of decline in PTH were similar (time: pulse=14.2±6.8 weeks, daily=12.2±7 weeks; rate: pulse=7.4±4.2 vs daily=8.4±4.2% PTH/week; P=NS). The serum calcium increased similarly in both groups. Hypercalcaemia (>2.9 mmol/l) was rare (pulse=3, daily=2 episodes). Conclusions: This study demonstrates that pulse and daily calcitriol are similarly effective and safe for the treatment of mild to moderate secondary hyperparathyroidism in CAPD patients despite higher peak levels of 1,25(OH)2-vitamin D with pulse therapy. Key words: calcitriol; calcium balance; CAPD; dialysis; hyperparathyroidism; renal osteodystrophy      

Changes in the physiology and fine structure of the taenia of the guinea-pig caecum following transplantation into the anterior eye chamber

1. The taenia of the guinea-pig caecum has been used as a model to study the re-establishment of autonomic innervation following transplantation into the anterior eye chamber. The ultrastructure, the histochemical localization of noradrenaline and acetylcholinesterase and the pharmacology of transmission to the taenia have been examined 1 day to 16 weeks following transplantation. Both ganglion-free strips of the taenia and caecal wall segments including the underlying Auerbach's plexus were used.2. Caecal wall preparations: nerve fibres from intramural ganglion cells retracted during the first 2 days following transplantation, but reappeared in the muscle soon afterwards. Adrenergic nerves from the iris formed terminals about ganglion cells at about 2-4 weeks. Both cholinergic excitatory and non-adrenergic (;purinergic') inhibitory transmission to the muscle was re-established by 2-4 days following transplantation.3. Taenia strip preparations: both adrenergic and cholinergic nerve fibres were demonstrated histochemically in muscle bundles by 2-4 weeks. Non-adrenergic inhibitory and cholinergic transmission was not re-established until 2-4 weeks following transplantation. There was an abnormally dense re-innervation of the muscle by adrenergic nerve fibres by about 8 weeks which is compared with the innervation of aganglionic bowel in Hirschsprung's disease.4. The origin of non-adrenergic inhibitory responses in the transplanted taenia is discussed and the results considered in relation to the re-innervation of transplants of the vas deferens and of intestine during early development.