Patterns of invasion and routes of tumor entry into the mandible by oral squamous cell carcinoma

BACKGROUND: An understanding of the patterns, spread, and routes of tumor invasion of the mandible is essential in deciding the appropriate level and extent of mandibular resection in oral squamous cell carcinoma. METHODS: A prospective study of histologic patterns of tumor invasion and routes of tumor entry into the mandible was performed in a consecutive series of 100 previously untreated patients. RESULTS: The pattern of tumor invasion of the mandible depended on the depth of invasion both in the hard (p =.001) and soft tissues (p =.001). There was evidence that the pattern of invasion was related to histologic prognostic indicators of the disease, such as extracapsular spread from invaded lymph nodes (p =.03). The route of tumor entry was at the point of abutment to the mandible (direct) in all 13 cases, invading the dentate part of the mandible. Fifty-five percent (23 of 42) of tumors invading the edentulous ridge entered through the occlusal (superior) surface. Direct entry to the mandible in the edentulous ridge was more likely for tumors arising in the tongue, floor of the mouth and the buccal mucosa compared with alveolar or retromolar sites (p =.003) CONCLUSIONS: Larger or more deeply invading tumors in the soft tissue are more likely to invade the mandible and show the more aggressive (invasive) form of tumor spread, reducing the options of a more conservative (rim) resection. Tumors tend to enter the mandible at the point of abutment, which in both the dentate and edentulous jaw is often at the junction of the reflected and attached mucosa. A point of tumor entry below the occlusal ridge or gingival crest should be assumed when planning rim or marginal resections of the mandible.     

Angiotensin II increases parathyroid hormone-related protein (PTHrP) and the type 1 PTH/PTHrP receptor in the kidney

Angiotensin II (AngII) participates in the pathogenesis of kidney damage. Parathyroid hormone (PTH)-related protein (PTHrP), a vasodilator and mitogenic agent, is upregulated during renal injury. The aim of this study was to investigate the potential relation between AngII and PTHrP system in the kidney. Different methods were used to find that both rat mesangial and mouse tubuloepithelial cells express PTHrP and the type 1 PTH/PTHrP receptor (PTH1R). In these cells, AngII increased PTHrP mRNA and protein production. In contrast, PTH1R mRNA was increased in mesangial cells and downregulated in tubular cells, but its protein levels were unmodified in both cells. AT(1) antagonist, but not AT(2), abolished AngII effects on PTHrP/PTH1R. The in vivo effect of AngII was further investigated by systemic infusion (a low dose of 50 ng/kg per min) into normal rats. In controls, PTHrP immunostaining was mainly detected in renal tubules. In AngII-infused rats, PTHrP staining increased in renal tubules and appeared in the glomerulus and the renal vessels. After AngII infusion, PTHR1 staining was markedly increased in all these renal structures at day 3 but remained elevated only in tubules at day 7. The AT(1) antagonist, but not the AT(2), significantly diminished AngII-induced PTHrP and PTHR1 overexpression in the renal tissue, associated with a decrease in tubular damage and fibrosis. The results indicate that AngII regulates renal PTHrP/PTH1R system via AT(1) receptors. These findings demonstrate that PTHrP upregulation occurs in association with the mechanisms of AngII-induced kidney injury.     

Participation in cognitively stimulating activities and risk of incident Alzheimer disease

Context  Frequent participation in cognitively stimulating activities has been hypothesized to reduce risk of Alzheimer disease (AD), but prospective data regarding an association are lacking. Objective  To test the hypothesis that frequent participation in cognitive activities is associated with a reduced risk of AD. Design  Longitudinal cohort study with baseline evaluations performed between January 1994 and July 2001 and mean follow-up of 4.5 years. Participants and Setting  A total of 801 older Catholic nuns, priests, and brothers without dementia at enrollment, recruited from 40 groups across the United States. At baseline, they rated frequency of participation in common cognitive activities (eg, reading a newspaper), from which a previously validated composite measure of cognitive activity frequency was derived. Main Outcome Measures  Clinical diagnosis of AD by a board-certified neurologist using National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association criteria and change in global and specific measures of cognitive function, compared by cognitive activity score at baseline. Results  Baseline scores on the composite measure of cognitive activity ranged from 1.57 to 4.71 (mean, 3.57; SD, 0.55), with higher scores indicating more frequent activity. During an average of 4.5 years of follow-up, 111 persons developed AD. In a proportional hazards model that controlled for age, sex, and education, a 1-point increase in cognitive activity score was associated with a 33% reduction in risk of AD (hazard ratio, 0.67; 95% confidence interval, 0.49-0.92). Results were comparable when persons with memory impairment at baseline were excluded and when terms for the apolipoprotein E 4 allele and other medical conditions were added. In random-effects models that controlled for age, sex, education, and baseline level of cognitive function, a 1-point increase in cognitive activity was associated with reduced decline in global cognition (by 47%), working memory (by 60%), and perceptual speed (by 30%). Conclusion  These results suggest that frequent participation in cognitively stimulating activities is associated with reduced risk of AD.      

Respective roles of inflammation and axonal breakdown in the regulation of peripheral nerve hemopexin: an analysis in rats and in C57BL/Wlds mice

We have previously demonstrated that one of the peripheral nerve responses to injury is the overexpression of hemopexin (HPX). Here, we demonstrate that Wallerian degeneration is required for this response, since HPX does not increase in C57BL/Wlds mice, which display a severely impaired Wallerian degeneration. We also show that HPX synthesis is dramatically increased in macrophages during their activation or after IL-6 stimulation. However, IL-6-driven HPX overexpression occurs in vivo and in vitro in the absence of substantial macrophage invasion. We conclude that, after nerve injury, HPX overexpression occurs first in Schwann cells as a result of axotomy and is subsequently regulated by inflammation. Furthermore, our results and those already described suggest that IL-6, synthesized by the various cell types producing HPX, control nerve HPX expression via paracrine and autocrine mechanisms.     

Analysis of particle deposition in the turbinate and olfactory regions using a human nasal computational fluid dynamics model.

The human nasal passages effectively filter particles from inhaled air. This prevents harmful pollutants from reaching susceptible pulmonary airways, but may leave the nasal mucosa vulnerable to potentially injurious effects from inhaled toxicants. This filtering property may also be strategically used for aerosolized nasal drug delivery. The nasal route has recently been considered as a means of delivering systemically acting drugs due to the large absorptive surface area available in close proximity to the nostrils. In this study, a computational fluid dynamics (CFD) model of nasal airflow was used with a particle transport and deposition code to predict localized deposition of inhaled particles in human nasal passages. The model geometry was formed from MRI scan tracings of the nasal passages of a healthy adult male. Spherical particles ranging in size from 5 to 50 microm were released from the nostrils. Particle trajectories and deposition sites were calculated in the presence of steady-state inspiratory airflow at volumetric flow rates of 7.5, 15, and 30 L/min. The nasal valve, turbinates, and olfactory region were defined in the CFD model so that particles depositing in these regions could be identified and correlated with their release positions on the nostril surfaces. When plotted against impaction parameter, deposition efficiencies in these regions exhibited maximum values of 53%, 20%, and 3%, respectively. Analysis of preferential deposition patterns and nostril release positions under natural breathing scenarios can be used to determine optimal particle size and flow rate combinations to selectively target drug particles to specific regions of the nose.     

Characterization of oxalic acid derivatives as new metabolites of metamizol (dipyrone) in incubated hen's egg and human.

Metamizol (dipyrone, 1), a widely used drug with effective analgesic and antispasmodic properties, shows severe side effects like agranulocytosis and anaphylactic shock reactions, the reasons of which are not known until today. After oral administration 1 is completely metabolized. All hitherto known metabolites have an intact pyrazolinone ring structure like the parent compound and are completely extractable from urine with polar organic solvents. However, only a fractional amount of the applied dosage can be recovered by this procedure. To clarify the reason of this deficit of unknown metabolites we followed the hypothesis of oxidative rupture of the heterocyclic ring during metabolism of 1. On the basis of former in vitro results we now were able to identify in quality three oxalic acid derivatives and one acetic acid phenylhydrazide as new metabolites of metamizol in the allantoic fluid (AF) of incubated hen's eggs as well as in human urine by means of GC-MS analysis and comparison with unequivocally synthesized authentic reference compounds. Whereas the oxamazide 7, the phenylhydrazide 8 and N-methyloxamic acid 9 are only present in trace concentrations and therefore cannot account for the deficit in the balance of metabolites, the oxalic acid monohydrazide 11 seems to be excreted in higher amount. But quantitative determination of this new metabolite would be required to answer the open questions concerning the biotransformation of metamizol and thereby to detect new facts about mode of action and side effects of this drug.     

Breast cancer risk and drinking water contaminated by wastewater: a case control study

Background  

Drinking water contaminated by wastewater is a potential source of exposure to mammary carcinogens and endocrine disrupting compounds from commercial products and excreted natural and pharmaceutical hormones. These contaminants are hypothesized to increase breast cancer risk. Cape Cod, Massachusetts, has a history of wastewater contamination in many, but not all, of its public water supplies; and the region has a history of higher breast cancer incidence that is unexplained by the population's age, in-migration, mammography use, or established breast cancer risk factors. We conducted a case-control study to investigate whether exposure to drinking water contaminated by wastewater increases the risk of breast cancer.     

Hospital inpatient self-administration of medicine programmes: a critical literature review

Aim The Department of Health, pharmaceutical and nursing bodies have advocated the benefits of self- administration programmes (SAPs), but their implementation within UK hospitals has been limited. Perceived barriers are: anticipated increased workload, insufficient resources and patient safety concerns. This review aims to discover if benefits of SAPs are supported in the literature in relation to risk and resource implications.Method Electronic databases were searched up to March 2004. Published English language articles that described and evaluated implementation of an SAP were included. Outcomes reported were: compliance measures, errors, knowledge, patient satisfaction, and nursing and pharmacy time.Results Most of the 51 papers reviewed had methodological flaws. SAPs varied widely in content and structure. Twelve studies (10 controlled) measured compliance by tablet counts. Of 7 studies subjected to statistical analysis, four demonstrated a significant difference in compliance between SAP and controls. Eight studies (5 controlled) measured errors as an outcome. Of the two evaluated statistically, only one demonstrated significantly fewer medication errors in the SAP group than in controls. Seventeen papers (11 controlled) studied the effect of SAPs on patients’ medication knowledge. Ten of the 11 statistically analysed studies showed that SAP participants knew significantly more about some aspects of their medication than did controls. Seventeen studies (5 controlled), measured patient satisfaction. Two studies were statistically analysed and these studies suggested that patients were satisfied and preferred SAP. Seven papers studied pharmacy time, three studied nursing time but results were not compared to controls.Conclusions The paucity of well-designed studies, flawed methodology and inadequate reporting in many papers make conclusions hard to draw. Conclusive evidence that SAPs improve compliance was not provided. Although patients participating in SAPs make errors, small numbers of patients are often responsible for a large number of errors. Whilst most studies suggest that SAPs increase patient’s knowledge in part, it is difficult to separate out the effect of the educational component of many SAPs. Most patients who participated in SAPs were satisfied with their care and many would choose to take part in a SAP in the future. No studies measured the total resource requirement of implementing and maintaining a SAP.