Best practice in primary care pathology: review 4

This fourth best practice review examines four series of common primary care questions in laboratory medicine are examined in this review: (1) safety monitoring for three common drugs; (2) use of prostate-specific antigen; (3) investigation of vaginal discharge; and (4) investigation of subfertility. The review is presented in question-answer format, referenced for each question series. The recommendations represent a precis of the guidance found using a standardised literature search of national and international guidance notes, consensus statements, health policy documents and evidence-based medicine reviews, supplemented by Medline Embase searches to identify relevant primary research documents. They are not standards but form a guide to be set in the clinical context. Most of them are consensus based rather than evidence based. They will be updated periodically to take account of new information.     

Micropermeability of current self-etching and etch-and-rinse adhesives bonded to deep dentine: a comparison study using a double-staining/confocal microscopy technique

Water sorption decreases the mechanical properties and the bond strengths of resin-bonded dentine. The aim of this study was to evaluate the micropermeability of several self-etching and etch-and-rinse adhesives. Optibond FL, Silorane, Scotchbond 1XT, G-Bond, and DC-Bond were bonded under simulated pulpal pressure. A 10 wt% solution of ammoniacal silver nitrate and a 1 wt% solution of rhodamine B were injected into the pulp chamber at 20 cm of water pressure. The dentine–adhesive interfaces were examined using a confocal scanning microscope. Micropermeability was detected in all the adhesives. DC-Bond, G-Bond, and Scotchbond 1XT showed voids along the resin-bonded interface. Silorane and Optibond FL showed an adhesive layer that was free from water trees and micropermeability. The double staining technique is a method that gives accurate results in the study of the resin-dentine micropermeability. Each class of adhesive has a different distribution of micropermeability. The higher the micropermeability, the higher the risk of defects at the resin–dentine interface, which may represent the pathway for hydrolytic and enzymatic degradation of resin–dentine bonds over time.     

Patterns of relapse in glioblastoma multiforme following concomitant chemoradiotherapy with temozolomide

Objective:

Different methods for contouring target volumes are currently in use in the UK when irradiating glioblastomas post operatively. Both one- and two-phase techniques are offered at different centres. 90% of relapses are recognised to occur locally when using radiotherapy alone. The objective of this evaluation was to determine the pattern of relapse following concomitant radiotherapy with temozolomide (RT-TMZ).

Methods:

A retrospective analysis of patients receiving RT-TMZ between 2006 and 2010 was performed. Outcome data including survival were calculated from the start of radiotherapy. Analysis of available serial cross-sectional imaging was performed from diagnosis to first relapse. The site of first relapse was defined by the relationship to primary disease. Central relapse was defined as progression of the primary enhancing mass or the appearance of a new enhancing nodule within 2 cm.

Results:

105 patients were identified as receiving RT-TMZ. 34 patients were not eligible for relapse analysis owing to either lack of progression or unsuitable imaging. Patterns of first relapse were as follows: 55 (77%) patients relapsed centrally within 2 cm of the original gadolinium-enhanced mass on MRI, 13 (18%) patients relapsed >4 cm from the original enhancement and 3 (4%) relapsed within the contralateral hemisphere.

Conclusion:

Central relapse remains the predominant pattern of failure following RT-TMZ. Single-phase conformal radiotherapy using a 2-cm margin from the original contrast-enhanced mass is appropriate for the majority of these patients.

Advances in knowledge:

Central relapse remains the predominant pattern of failure following chemoradiotherapy for glioblastomas.In the UK, high-grade gliomas have an incidence of approximately 7.7 per 100 000 individuals per year, resulting in around 4800 new cases per year [1]. The current standard treatment for good performance status patients with glioblastomas is maximal safe resection followed by chemoradiotherapy, then 6 months of adjuvant chemotherapy using temozolomide (RT-TMZ). This approach was defined by the pivotal European Organisation for Research and Treatment of Cancer/National Cancer Institute of Canada (EORTC/NCIC) randomised study first published by Stupp et al in 2005 [2,3]. The addition of temozolomide to radiotherapy, 60 Gy in 30 fractions, improved overall survival at 1 year from 10.9% to 27.2% and this survival advantage was maintained at 5 years [1.9% vs 9.8% (p<0.0001)].Although RT-TMZ has become standard practice, radiotherapy delivery and target delineation variations still exist. Historically, large field radiotherapy was based on post-mortem studies confirming tumour cells within the oedema surrounding the contrast-enhanced mass as defined by CT [4]. A margin of ≥3 cm beyond oedema is required to ensure complete coverage of all tumour cells based on the post-mortem studies [5]. A two-phase technique was commonly used to achieve this and a study analysing pattern recurrence recommended a boost volume using a 4-cm field edge from the contrast-enhanced mass defined on CT [6]. Subsequent Radiation Therapy Oncology Group (RTOG) guidelines specified a two-phase approach which incorporated oedema with a 2-cm margin in the first phase and subsequent boost to residual disease with a margin [7,8] (RTOG 0525 and 0825 trials). However, the studies carried out by Stupp et al [2,3] defined modern-day practice and 60 Gy in 30 fractions was delivered in a single phase. The protocol recommended a planning target volume (PTV) of 2–3 cm from the enhancing tumour or the tumour bed. This is based on several published series suggesting that the majority of relapses occur within 2 cm of the original tumour edge, indicating that it may be unnecessary to include peritumoral oedema to reduce the risk of future relapse [9,10].Reducing the volume of brain exposed to radiotherapy could help to minimise toxicity and preserve quality of life. Through high-quality image fusion, improved dosimetry and more accurate treatment delivery many institutions have adapted protocols to permit reduction of the dose given to normal tissue [11–13]. The aim of this study was to evaluate the pattern of relapse following RT-TMZ using conformal radiotherapy to aid the development of a protocol using image-guided intensity-modulated radiotherapy (IMRT).     

High-dose thiamine supplementation improves glucose tolerance in hyperglycemic individuals: a randomized, double-blind cross-over trial

Purpose

To assess the effect of high-dose oral thiamine supplements on glucose tolerance in patients with impaired glucose metabolism.

Methods

Twelve hyperglycemic subjects (10 cases of impaired glucose tolerance and 2 new cases of type 2 diabetes) completed this randomized, double-blind trial, where all participants received both placebo and thiamine capsules (3 × 100 mg/day) for 6 weeks in a cross-over manner. The main endpoint was changes in 2-h plasma glucose. Fasting plasma glucose and insulin, 2-h plasma insulin, the hemostatic model assessment of insulin resistance (HOMA-IR), renal function measurement and thiamin status were also evaluated at the commencement and completion of each treatment period.

Results

Thiamine supplementation resulted in significant decrease in 2-h plasma glucose relative to baseline (8.78 ± 2.20 vs. 9.89 ± 2.50 mmol/l, p = 0.004), with no significant change in the placebo arm. Fasting plasma glucose and insulin, and HOMA-IR increased significantly from baseline after 6 weeks in the placebo arm (p = 0.003, p = 0.04 and p = 0.02, respectively). These variables did not change with thiamine supplementation. There were no significant changes in 2-h plasma insulin or renal function marker, within or between arms.

Conclusion/interpretation

Supplementation with high-dose thiamine may prevent deterioration in fasting glucose and insulin, and improve glucose tolerance in patients with hyperglycemia. High-dose thiamine supplementation may prevent or slow the progression of hyperglycemia toward diabetes mellitus in individuals with impaired glucose regulation.     

Effect of bracket and wire composition on frictional forces

Previous work on friction has considered movement of single teeth along an archwire. The aim of this investigation was to consider friction in buccal segment attachments during overjet reduction involving sliding mechanics. A buccal segment model was constructed to compare friction in steel and ceramic brackets, using steel and nickel titanium wires of two sizes along with a new experimental polymeric wire. The results indicate that friction during overjet reduction is minimized by using larger dimension rectangular wires and by using steel rather than nickel titanium. Comparing steel with ceramic brackets in series, the latter show greater frictional resistance, but only when used with the smaller rectangular wires. The combined effect of environment, ligation, bracket, and archwire significantly reduced the difference. Clinically, there may, therefore, be little to choose between steel and ceramic brackets in the buccal segments, with wire choice as determined by tooth displacement being more important. Comparison of the results with those obtained using single brackets illustrates the problems of interpreting results from friction experiments. The polymeric archwire in its present form was found to be unsuitable for use in orthodontics.     

An in vitro investigation of microtensile bond strengths of two dentine adhesives to caries-affected dentine

OBJECTIVES: To compare the micro-tensile bond strengths of two different adhesive systems (ABF (Clearfil Protect Bond), Kuraray Medical Inc., Tokyo, Japan) and Prime & Bond NT (PBNT, Dentsply, Konstanz, Germany) bonded to caries-affected dentine retained after chemo-mechanical caries removal using Carisolv gel, with that retained after excavation using conventional hand instrumentation. METHOD: Twenty, adult, human extracted carious teeth were used in this split tooth study with bur-cut cavities in sound dentine acting as controls. After clinical caries excavation, the occlusal cavities in each experimental group were restored with either bonding system plus composite. Matchstick-shaped samples through the bond interfaces were sectioned and microtensile bond strengths recorded. Scanning electron microscopy (SEM) was used to ascertain the mode of failure at the restoration-dentine interface. RESULTS: Statistical analysis of the bond strength data showed that for the ABF group, there was no difference in bond strengths between the controls and Carisolv group but these values were significantly higher than those for the hand-excavated samples. PBNT samples showed no significant differences in any of the three test groups, with wider ranging data sets. SEM analysis indicated a variety of failures at the interface including cohesive failures within the caries-affected dentine itself. CONCLUSIONS: From the data generated by this study it could be concluded that microtensile bond strengths of PBNT/composite restorations to caries-affected dentine in clinical cavities were statistically comparable to those to sound dentine. In the ABF/composite restored group (self-etched), the use of conventional hand excavation appeared to weaken the bond strength to the remaining caries-affected dentine. However, the use of Carisolv gel excavation did not compromise bond strengths to caries-affected dentine in either group tested.     

Should infants be screened for anaemia? A prospective study investigating the relation between haemoglobin at 8, 12, and 18 months and development at 18 months.

AIMS: To investigate the relation between haemoglobin in children followed longitudinally from 8 to 18 months, and developmental outcome at 18 months. METHODS: The Avon Longitudinal Study of Pregnancy and Childhood (ALSPAC) is a longitudinal survey of a geographically defined population of children born in 1991-92. In a randomly selected subsample, blood samples were assayed for Hb at 8, 12, and 18 months; a developmental assessment was carried out at 18 months on 1141 children using the Griffiths Scales of Mental Development. RESULTS: There was a strong quadratic association between Hb at 8 months and performance on the locomotor subscale at 18 months. Average scores increased with increasing Hb up to 95 g/l; there was little additional developmental benefit in Hb levels beyond 95 g/l. Infants with Hb <95 g/l at 8 months of age scored on average 6 points lower on the locomotor subscale than infants with Hb >/= 95 g/l; infants with Hb <90 g/l at 8 months scored 12 points lower on the locomotor subscale than children with Hb >/= 90 g/l. CONCLUSIONS: Low Hb concentrations (相似文献   

Epidemiological and physiological approaches to understanding the etiology of pediatric obesity: finding the needle in the haystack

Recent increases in the prevalence of childhood obesity have created an urgent need for preventive strategies, but such strategies in turn depend on an improved understanding of the etiology of pediatric obesity. There is a dearth of evidence of the cause of pediatric obesity at present, with much of the literature of limited quality, inconclusive, and contradictory. The present review highlights the paradox of energy imbalance-its apparent simplicity but actual complexity-and the difficulties in etiologic research that arise from this complexity. The review identifies a number of emerging problems for etiologic studies. The review also makes a number of proposals that might improve future etiologic studies and provides a framework for integrating the diverse body of evidence of etiology that will become available in future. Gathering improved evidence of etiology, and then integrating and interpreting it, will take many years. In the meantime, an emphasis on developing more effective preventive interventions is necessary.     

Cytokine profiles in serum and peritoneal fluid from infertile women with and without endometriosis

OBJECTIVE: To study the serum and peritoneal fluid cytokine profiles in infertile women with minimal/mild active endometriosis. METHODS: Fifty-seven consecutive infertile women undergoing laparoscopy for unexplained infertility had peritoneal fluid and serum samples obtained at the time of laparoscopy. The levels of interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-1 beta (IL-1 beta), vascular endothelial growth factor (VEGF), tumor necrosis factor-alpha (TNF-alpha), monocyte chemotatic protein-1 (MCP-1), RANTES, platelet derived growth factor (PDGF), soluble Fas (sFas), and soluble Fas Ligand (sFasL) in peritoneal fluid and serum were measured to compare the concentration in both biological fluids, in women who have minimal/mild red endometriosis using women with no endometriosis as controls. RESULTS: Peritoneal fluid levels of MCP-1, IL-8 and IL-6 were significantly higher in the endometriosis group (P < 0.012, P = 0.003, and P = 0.015, respectively). There was no significant difference in the peritoneal fluid levels of IL-1 beta, TNF-alpha, RANTES, VEGF, PDGF, sFas and sFasL in the two groups. Although serum levels of IL-8 were higher in women with endometriosis, the difference was not significant (P = 0.07). Serum levels of PDGF, IL-6, RANTES, IL-1 beta, TNF-alpha, and sFas, were not significantly different in the two groups. CONCLUSION: The elevated levels of MCP-1, IL-6, and IL-8 in peritoneal fluid but not serum may indicate the importance of local macrophage activating factors in the pathogenesis of endometriosis.