Complete spontaneous regression of a metastatic melanoma of the mandible: a case report and follow-up recommendations.

Regression of metastatic melanoma is very rare and occurs in only 0.23% of cases. Metastasis to the oral cavity is particularly uncommon and accounts for only 1-3% of all oral malignancies. This report presents a case of spontaneous and complete regression of a metastatic melanoma in the mandibular ramus. The patient remains asymptomatic more than 2 years after diagnosis. The patient was followed up regularly. It is recommended that further surveillance imaging be performed in asymptomatic patients following discussion with the surgical and oncological teams. This type of surveillance, together with new systemic treatments, is advocated due to its potential to increase long-term survival even after relapse.

Trabectedin in Advanced High-Grade Uterine Leiomyosarcoma: A Case Report Illustrating the Value of (18)FDG-PET-CT in Assessing Treatment Response.

We report the case of a 60-year-old woman with metastatic high-grade uterine leiomyosarcoma who achieved a delayed response to second-line therapy with the marine-derived drug trabectedin (Yondelis(®), PharmaMar). We used 2-deoxy-2-[(18)F] fluorodeoxyglucose (FDG)-positron emission tomography (PET-CT) imaging as a tool for response monitoring in parallel with conventional re-staging according to Response Evaluation Criteria in Solid Tumours (RECIST) using computed tomography (CT). We illustrate the role of serial (18)FDG-PET-CT imaging in the functional assessment of tumour response. Three cycles after commencement of trabectedin treatment, a reduction of the maximum standardized uptake value (SUVmax) of the solid component of the pelvic mass was observed, indicating a cystic or necrotic response in the tumour to trabectedin. After 7 cycles of treatment, on (18)FDG-PET-CT there was clear evidence of ongoing disease improvement: the solid pelvic components were at worst stable, with an unchanged SUVmax, and possibly marginally reduced in size, while the pulmonary metastases had further reduced in size and become FDG negative; the bony metastases were stable. After a total of 13 cycles of treatment, administered over 13 months, the patient showed signs of progression on an (18)FDG-PET-CT scan. The safety profile of trabectedin remained manageable, showing no evidence of cumulative toxicity and being associated with a preserved quality of life. This report illustrates potential limitations of RECIST in response assessments and the critical role of serial (18)FDG-PET-CT imaging in assessing response to trabectedin treatment. Therefore, we propose that (18)FDG-PET-CT may improve the assessment of response to trabectedin in selected patients.

Continuous low-dose cyclophosphamide and methotrexate combined with celecoxib for patients with advanced cancer.

BACKGROUND: Combined therapy of metronomic cyclophosphamide, methotrexate and high-dose celecoxib targeting angiogenesis was used in a phase II trial. METHODS: Patients with advanced cancer received oral cyclophosphamide 50 mg o.d., celecoxib 400 mg b.d. and methotrexate 2.5 mg b.d. for two consecutive days each week. Response was determined every 8 weeks; toxicity was evaluated according to CTC version 2.0. Plasma markers of inflammation, coagulation and angiogenesis were measured. RESULTS: Sixty-seven of 69 patients were evaluable for response. Twenty-three patients had stable disease (SD) after 8 weeks, but there were no objective responses to therapy. Median time to progression was 57 days. There was a low incidence of toxicities. Among plasma markers, levels of tissue factor were higher in the SD group of patients at baseline, and levels of both angiopoietin-1 and matrix metalloproteinase-9 increased in the progressive disease group only. There were no changes in other plasma markers. CONCLUSION: This metronomic approach has negligible activity in advanced cancer albeit with minimal toxicity. Analysis of plasma markers indicates minimal effects on endothelium in this trial. These data for this particular regimen do not support basic tenets of metronomic chemotherapy, such as the ability to overcome resistant tumours by targeting the endothelium.

Methylphenidate for gait impairment in Parkinson disease: a randomized clinical trial.

BACKGROUND: There is a paucity of therapies for gait impairment in Parkinson disease (PD). Open-label studies have suggested improved gait after treatment with methylphenidate (MPD). OBJECTIVE: To evaluate the efficacy of MPD for the treatment of gait impairment in PD. METHODS: Twenty-seven subjects with PD and moderate gait impairment were screened for this 6-month placebo-controlled, double-blind study. Subjects were randomly assigned to MPD (maximum, up to 80 mg/day) or placebo for 12 weeks and crossed over after a 3-week washout. The primary outcome measure was change in a gait composite score (stride length + velocity) between groups at 4 and 12 weeks. Secondary outcome measures included changes in motor function, as measured by the Unified Parkinson's Disease Rating Scale (UPDRS), Freezing of Gait Questionnaire (FOGQ), number of gait-diary freezing episodes, and measures of depression, sleepiness, and quality of life. Three-factor repeated-measures analysis of variance was used to measure changes between groups. RESULTS: Twenty-three eligible subjects with PD were randomized and 17 completed the trial. There was no change in the gait composite score or treatment or time effect for any of the variables. Treatment effect was not modified by state or study visit. Although there was a trend for reduced frequency of freezing and shuffling per diary, the FOGQ and UPDRS scores worsened in the MPD group compared to placebo. There was a marginal improvement in some measures of depression. CONCLUSIONS: MPD did not improve gait and tended to worsen measures of motor function, sleepiness, and quality of life. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence for the lack of benefit of MPD on PD-associated gait impairment. CLINICAL TRIAL REGISTRATION: NCT00526630.

An unusual presentation of an ectopic third molar in the condylar region.

We describe the case of a 53-year-old patient who presented with an intermittent discharging sinus on his face which, following a number of investigations, was found to be secondary to an ectopic third molar in the condylar region. The ectopic tooth was surgically removed with complete resolution of the facial swelling. This case highlights the possibility of dental pathology presenting with completely unrelated signs and symptoms, and the importance of the clinician maintaining an open mind when it comes to the differential diagnosis of such a presentation.

Modelling the bacterial communities associated with cystic fibrosis lung infections.

In many human diseases that cystic fibrosis (CF) patients suffer from, for example, lung infections, bacteria have been considered to grow as biofilms. The ability of key CF pathogens such as Pseudomonas aeruginosa to resist antibiotic therapies may be due to the poor drug penetration of these biofilms. The overall aim of this study was to develop biofilm models in vitro that resembled the bacterial species composition of CF sputa. Here, this was a step towards a longer term goal of forming multiple bacterial biofilm models in vitro that would serve, in turn, as better assays of antibiotic susceptibilities than conventionally grown cells. Biofilm models were constructed from 31 CF sputum samples, using a modified microtitre plate assay. Three forms of assessment of these biofilms were made, namely, the mass, microscopic analysis and species composition. Species composition in sputa and biofilms, characterised by terminal restriction fragment length polymorphism (T-RFLP) analysis of ribosomal gene polymerase chain reaction (PCR) products amplified from directly extracted nucleic acids, indicated that the bacterial community in sputa was well reproduced in the biofilm models. Typically, fresh sputa contained 4.6 +/- 2.3 bacterial species, with the species number decreasing to 4.0 +/- 1.6 over 5 days-this was not statistically significant (p = 0.29). This study outlines a novel methodology by which to generate and study bacterial biofilms communities. It is also hoped that the versatility of this in vitro approach, combined with its simplicity and high reproducibility, will make it an effective system to study CF sputum biofilm development and, in the longer term, serve as a means of assessing antibiotic susceptibilities.

A phase I trial of ispinesib, a kinesin spindle protein inhibitor, with docetaxel in patients with advanced solid tumours.

The aim of this study is to define the maximum tolerated dose (MTD), safety, pharmacokinetics (PKs) and efficacy of ispinesib (SB-715992) in combination with docetaxel. Patients with advanced solid tumours were treated with ispinesib (6-12 mg m(-2)) and docetaxel (50-75 mg m(-2)). Docetaxel was administered over 1 h followed by a 1-h infusion of ispinesib on day 1 of a 21-day schedule. At least three patients were treated at each dose level. Blood samples were collected during cycle 1 for PK analysis. Clinical response assessments were performed every two cycles using RECIST guidelines. Twenty-four patients were treated at four dose levels. Prolonged neutropaenia and febrile neutropaenia were dose limiting in six and two patients, respectively. The MTD was ispinesib 10 mg m(-2) with docetaxel 60 mg m(-2). Pharmacokinetic assessment demonstrated concentrations of ispinesib and docetaxel, consistent with published data from single agent studies of the drugs. Seven patients (six hormone refractory prostate cancer (HRPC), one renal cancer) had a best response of stable disease (>or=18 weeks). One patient with HRPC had a confirmed >50% prostatic-specific antigen decrease. The MTD for ispinesib and docetaxel was defined and the combination demonstrated an acceptable toxicity profile. Preliminary PK data suggest no interaction between ispinesib and docetaxel.

Effect of fuel and lube oil sulfur on the performance of a diesel exhaust gas continuously regenerating trap.

The continuously regenerating trap (CRT) is a diesel exhaust emission control that removes nearly all diesel particulate matter on a mass basis, but under some circumstances oxidation of sulfur leads to the formation of nanoparticles. The objective of the four year study was to determine CRT performance under controlled, real-world, on-road conditions, and to develop quantitative relationships between fuel and lubrication oil sulfur concentration and particle number exhaust emissions. It was shown that nanoparticle emissions are minimized by the use of ultralow sulfur fuels and specially formulated low sulfur lubrication oil. Nanoparticle emissions increased with higher exhaust temperatures. Fuel and lubrication oil sulfur increased the particle concentration by, on average, 36 x 10(6) and 0.14 x 10(6) part/cm3 for each 1 ppm increase in sulfur. On the other hand there was a decrease in nanoparticle emissions by the CRT as the system aged.

Thoracic paravertebral block for analgesia following liver mass radiofrequency ablation.

A 66-year-old man presented for a second attempt of radiofrequency ablation of a metastatic carcinoid liver lesion. The first attempt using intravenous sedation was unsuccessful because of inadequate pain control and subsequent patient combativeness. Despite fentanyl being given during general anaesthesia, the patient complained of severe right flank pain after emergence. A thoracic paravertebral block was performed without complication and the patient's pain decreased to "3 out of 10" on a standard 10-point scale after 10 min, and "0 out of 10" after 30 min. The patient's pain score remained 0 throughout the following day, and no further analgesics were required. Thoracic paravertebral block can provide complete and lasting analgesia following hepatic radiofrequency ablation, and warrants further study for patients undergoing hepatic radiological interventions.

An evaluation of dairy producer emergency preparedness and farm security education.

Dairy producer education on securing the milk and meat supply is important to reduce the food system's vulnerability to contamination, and reduce the likelihood for disease transmission onto and within the farm. The purpose of this project was to develop and test a producer-audience curriculum on emergency preparedness and biosecurity awareness. Forty-three attendees from 3 organizations responded to pre- and posttests and a course evaluation. After the program, most of the participants found the program relevant (95%), that it provided practical solutions to biosecurity (97%), were very likely to assess their farms for biosecurity and security (70%), and would suggest the program to other producers (98%). Participants who strongly agreed that the program was relevant and provided practical solutions to biosecurity were very likely to assess their farms. Awareness and knowledge are the first steps toward changing attitudes and behavior and can be accomplished with directed, relevant, practical educational programs.

Social objectives in cancer care: the example of palliative day care.

Social objectives are poorly specified and evaluated in cancer care. Palliative day care is an example where social objectives are often identified but research has focused on health-care outcomes. A literature review identifies four types of social objective: emotional and spiritual care, general social care, services for families and carers and creative arts. Social objectives include: distinguishing between therapeutic work and leisure and supportive interventions, promoting service continuity, reducing social isolation, increasing social interaction, reassuring introduction to palliative care, rehearsal of reactions to illness with a sympathetic audience, integration of families and carers into care services, respite for carers and creative work for three separable objectives. It is argued that interventions to achieve social objectives may be defined and evaluated in a measurable way. Similarly, social objectives and interventions can be specified at other stages in the cancer journey.

Temozolomide in the treatment of solid tumours: current results and rationale for dosing/scheduling.

This review examines the current evidence for the use of temozolomide in the treatment of solid tumours. The possible molecular and clinical advantages of temozolomide are identified and the molecular mechanism of temozolomide resistance is explored. Attempts to maximise efficacy have led to manipulation of both dosage and drug scheduling and the evidence for the various strategies is reviewed. Finally, the potential role of combination therapy is considered.

Outcome evaluation of a high school smoking reduction intervention based on extracurricular activities.

BACKGROUND: An outcome evaluation of a high school tobacco control intervention using extracurricular activities developed by teachers and students is reported. METHODS: Eligible subjects (n = 3,028) had participated in a randomized trial of an elementary school smoking prevention curriculum. Their high schools were matched in pairs; one school in each pair was randomly assigned to the intervention condition, the second to a "usual-care" control condition. Data were collected at the end of Grades 9 and 10. RESULTS: For Grade 8 never smokers, regular smoking rates were significantly lower for males from intervention schools (9.8 vs 16.2%, P = 0.02) at the end of Grade 10. There were no significant differences among Grade 10 smoking rates for females, or for students of either gender with previous smoking experience in Grade 8. CONCLUSIONS: The extracurricular activities approach to tobacco control is practical to implement and has promise.

Gardner's syndrome - a case report.

Gardner's syndrome is the association of multiple colonic polyps (familial adenomatous polyposis coli - FAP) with sebaceous cysts and jaw osteomas. The significance of this dominantly inherited condition to the dentist is that the colonic polyps usually undergo malignant change by the fourth decade and the extra-intestinal lesions may be apparent before those in the bowel. As such, early detection of multiple jaw osteomas and/or multiple sebaceous cysts (particularly on the scalp) may lead to appropriate further investigation and treatment which might be life saving. Diagnosis of this condition also has implications for other family members.

A comparison of the imaging properties of CCD-based devices used for small field digital mammography.

The objective imaging characteristics of three systems that use charge coupled devices (CCD) for small-field digital mammography (SFDM) have been compared in terms of spatial resolution and signal to noise ratio. The results indicate that although they are designed for nominally the same tasks of stereotactic localization and spot imaging these detectors have significantly differing physical imaging properties. Imaging system design parameters such as the phosphor screen type and thickness, screen configuration and method of optically coupling the phosphor to the CCD have significant effects on the imaging performance of the detectors.

Thermodynamics of catalytic formation of dimethyl ether from methanol in acidic zeolites.

We present a theoretical study of the formation of the first intermediate, dimethyl ether, in the methanol to gasoline conversion within the framework of an ab initio molecular dynamics approach. The study is performed under conditions that closely resemble the reaction conditions in the zeolite catalyst including the full topology of the framework. The use of the method of thermodynamic integration allows us to extract the free-energy profile along the reaction coordinate. We find that the entropic contribution qualitatively alters the free-energy profile relative to the total energy profile. Different transition states are found from the internal and free energy profiles. The entropy contribution varies significantly along the reaction coordinate and is responsible for stabilizing the products and for lowering the energy barrier. The hugely inhomogeneous variation of the entropy can be understood in terms of elementary processes that take place during the chemical reaction. Our simulations provide new insights into the complex nature of this chemical reaction.

Treadmill exercise during adenosine infusion is safe, results in fewer adverse reactions, and improves myocardial perfusion image quality.

BACKGROUND: Combining low-level treadmill exercise with adenosine infusion may result in fewer bradyarrhythmic complications by increasing sympathetic tone and may improve myocardial perfusion image quality by decreasing background activity. METHODS: Patients referred for outpatient pharmacologic stress myocardial perfusion imaging performed simultaneous treadmill exercise (mean 2.2 metabolic equivalents) throughout 6-minute adenosine infusion (adenosine-exercise n = 507). Patients unable to exercise and those with left bundle branch block received adenosine infusion alone (adenosine-nonexercise n = 286). Adverse reaction data were collected on all patients and compared by sex. Background-to-target activity was calculated in a blinded fashion on 200 randomly selected patients. RESULTS: During the period from April 1996 to December 1998, 507 patients (64%) underwent adenosine-exercise testing, whereas 286 (36%) underwent adenosine-nonexercise testing. Hypotensive and arrhythmic (atrioventricular block, sinus bradycardia, and new onset atrial fibrillation or flutter) adverse reactions occurred less often during adenosine-exercise than during adenosine-nonexercise. Neither death nor myocardial infarction occurred in either group. In the adenosine-exercise group, 2.8% of patients experienced an adverse reaction versus 5.6% of the adenosine-nonexercise group (P = .04). The reduction in adverse reactions occurred in both men and women, although women had significantly more adverse reactions than men (5.7% vs 1.8%, P = .004). Liver/heart and gut/heart ratios were lower in the adenosine-exercise group (1.05+/-0.42 vs. 1.21+/-0.55 , P = .01; 0.61+/-0.21 vs. 0.69+/-0.24, P = .03, respectively). CONCLUSIONS: Compared with adenosine infusion alone, combining low-level treadmill exercise with adenosine in outpatients is safe, better tolerated, and improves image quality. Women were more likely to experience adverse reactions than men.