Prediction modelling using routine clinical parameters to stratify survival in Malignant Pleural Mesothelioma patients undergoing cytoreductive surgery

Introduction

Malignant pleural mesothelioma (MPM) is an uncommon cancer with a poor prognosis and heterogeneous survival. Surgery for MPM is offered in some specialist centers to highly selected patients. A previously described classification and regression tree (CART) model stratified survival in unselected MPM patients using routinely collected clinical data. This study aimed to examine the performance of this CART model on a highly selected surgical population.

Effect of CYP3A4, CYP3A5, and ABCB1 Polymorphisms on Intravenous Tacrolimus Exposure and Adverse Events in Adult Allogeneic Stem Cell Transplant Patients

Pharmacogenetics influences oral tacrolimus exposure; however, little data exist regarding i.v. tacrolimus. We investigated the impact of genetic polymorphisms in CYP3A4, CYP3A5, and ABCB1 on i.v. tacrolimus exposure and toxicity in adult patients receiving an allogeneic hematopoietic stem cell transplant for hematologic malignancies. Germline DNA was extracted from buccal swabs and genotyped for CYP3A4, CYP3A5, and ABCB1 polymorphisms. Continuous i.v. infusion of tacrolimus .03 mg/kg/day was initiated on day +5 post-transplant, and steady-state blood concentrations were measured 4days later. We evaluated the association between phenotypes and prevalence of nontherapeutic target concentrations (below or above 5 to 15 ng/mL) as well as tacrolimus-related toxicities. Of 63 patients, 28.6% achieved the target concentration; 71.4% were >15ng/mL, which was more common in CYP3A4 intermediate/normal metabolizers (compared with rapid) and those with at least 1 ABCB1 C2677T loss-of-function allele (P < .05). ABCB1 C2677T was significantly associated with concentrations >15ng/mL (odds ratio, 6.2; 95% confidence interval, 1.8 to 23.6; P = .004) and tacrolimus-related toxicities (odds ratio, 7.5; 95% confidence interval, 1.6 to 55.2; P = .02). ABCB1 C2677T and CYP3A4 are important determinants of i.v. tacrolimus exposure, whereas ABCB1 C2677T also impacts tacrolimus-related toxicities in stem cell transplants.     

Characterization of root surface periodontal ligament following avulsion, severe intrusion or extraction: preliminary observations

Abstract –  This study employed novel topographic and histological techniques to assess remaining periodontal ligament (PDL) in a convenience sample of avulsed and intruded human permanent incisors and extracted premolars. Seventeen human teeth (eight avulsed, five severely intruded and four uninjured extracted) were evaluated for the distribution and physical characteristics of adherent root surface PDL. The topographic distribution of PDL was assessed by staining roots with malachite green and determining the proportion of remaining PDL within selected regions on four aspects of each tooth. In order to characterize mechanical damage to PDL, serial transverse sections of roots were stained with hematoxylin and eosin and examined at magnifications of 40× to 800×. The sections were photographed and imaging software was used to calculate the percentage of remaining PDL in the circumference of each root section. Topographic analysis demonstrated that 54% of the PDL remained on roots of avulsed and severely intruded incisors and 36% of the PDL remained on the extracted single-rooted premolars. Examination of serial transverse root sections revealed that 58% of the PDL remained on roots of avulsed or severely intruded incisors and 54% on extracted premolars. Avulsed and severely intruded incisors demonstrated similar amounts of retained PDL. In both injuries, almost half of the root surface was denuded of PDL.     

Dietary influences on the formation of dental calculus in rats

Eleven diets were evaluated for their ability to produce dental calculus in albino rats. A diet containing 50 % cornstarch, 32 % nonfat dry milk, 3 % liver powder, 5 % celluflour, 1 % cottonseed oil, 5 % powdered sucrose, 1 % calcium chloride dihydrate, 2.7 % sodium dihydrogen phosphate monohydrate, and 0.3 % magnesium sulfate (Francis and Briner 1969) was remarkably effective. On the basis of a 0–3 calculus scoring system, an average score of 2.36 (S.D. = 0.65) resulted after 4 weeks' exposure to the above diet and, after 8 weeks, the average score was 2.59 (S.D. = 0.56).
While it was found that, in general, high cornstarch and milk powder diets were associated with higher calculus scores, no other diet remotely approached the above diet in calculogenicity.     

Control of brushing variables for the in vitro assessment of toothpaste abrasivity using a novel laboratory model

OBJECTIVES: Design and construct a tooth-brushing simulator incorporating control of brushing variables including brushing force, speed and temperature, thereby facilitating greater understanding of their importance in toothpaste abrasion testing methodologies. METHODS: A thermostable orbital shaker was selected as a base unit and 16- and 24-specimen brushing rigs were constructed to fit inside, consisting of: a square bath partitioned horizontally to provide brushing channels, specimen holders for 25 mm diameter mounted specimens to fit the brushing channels and individually weighted brushing arms, able to support four toothbrush holders suspended over the brushing channels. Brush head holders consisted of individually weighted blocks of Delrin, or PTFE onto which toothbrush heads were fixed. Investigating effects of key design criteria involved measuring abrasion depths of polished human enamel and dentine. RESULTS: The brushing simulator demonstrated good reproducibility of abrasion on enamel and dentine across consecutive brushing procedures. Varying brushing parameters had a significant impact on wear results: increased brushing force demonstrated a trend towards increased wear, with increased reproducibility for greater abrasion levels, highlighting the importance of achieving sufficient wear to optimise accuracy; increasing brushing temperature demonstrated increased enamel abrasion for silica and calcium carbonate systems, which may be related to slurry viscosities and particle suspension; varying brushing speed showed a small effect on abrasion of enamel at lower brushing speed, which may indicate the importance of maintenance of the abrasive in suspension. CONCLUSIONS: Adjusting key brushing variables significantly affected wear behaviour. The brushing simulator design provides a valuable model system for in vitro assessment of toothpaste abrasivity and the influence of variables in a controlled manner. Control of these variables will allow more reproducible study of in vitro tooth wear processes.     

Temporal summation of pain characterizes women but not men with temporomandibular disorders

AIMS: To examine differences in temporal summation of mechanically evoked pain between women and men suffering from chronic pain associated with temporomandibular disorders (TMD), as well as between male TMD patients and healthy controls. METHODS: Series of 10 repetitive, mildly noxious mechanical stimuli were applied to the fingers of 27 female TMD patients, 16 male TMD patients, and 20 healthy men. The subjects rated the pain intensity caused by the 1st, 5th, and 10th stimulus in the series. Pain ratings were analyzed by 3-way repeated-measures analysis of variance. RESULTS: Pain ratings increased significantly with stimulus repetition for the female TMD patients (P < .001). Women with TMD exhibited significantly greater temporal summation of pain than TMD men (P < .001). Neither the healthy men nor the male TMD patients exhibited significant increases in pain perception with repetitive stimulation. In the female TMD patient group, perceptual pain magnitudes were higher with an interstimulus interval of 2 seconds rather than 10 seconds (P < .005). CONCLUSION: These findings suggest that central nociceptive processing upregulation is likely to contribute to TMD pain for women but is not a factor for