A novel characterized multi-drug-resistant Pseudocitrobacter sp. isolated from a patient colonized while admitted to a tertiary teaching hospital.

BACKGROUND: Reports of nosocomial infections typically describe recognised microorganisms. Here, a novel bacterial species was isolated, based on rectal swab screening for carbapenemases post-admission, then phenotypically and genetically characterized. METHODS: Sensititre, Vitek and API kits, MALDI and Illumina MiSeq were employed before profiles and phylogeny were compared with other related species. FINDINGS: Determined to be a possible Enterobacterales, the isolate was found to have 99.7% 16s rRNA identity to Pseudocitrobacter corydidari; an Asian cockroach-associated species. Given the highly conserved/low variability of 16S rRNA genes in Enterobacterales, average nucleotide identity (ANI) analysis compared the new isolate's genome with those of 18 Enterobacteriaceae species, including confirmed species of Pseudocitrobacter and unnamed Pseudocitrobacter species in the SILVA database. Of these, Pseudocitrobactercorydidari had the highest ANI at 0.9562. The published genome of the only known isolate of P.corydidari does not include Antimicrobial Resistance Genes (ARGs), with exception of potential drug efflux transporters. In contrast, our clinical isolate bears recognised antimicrobial resistance genes, including Klebsiella pneumoniae carbapenemase. The associated genome suggests resistance to carbapenems, ß-lactams, sulfonamides, fluoroquinolones, macrolides, aminoglycosides and cephalosporins. Phenotypic antimicrobial resistance was confirmed. CONCLUSION: Evident variations in ARG profiles, human colonization and origin in a clinically relevant niche that is geographically, physically and chemically disparate lend credibility for divergent evolution or, less likely, parallel evolution with P. corydidari. Genome data for this new species have been submitted to GENBANK using the proposed nomenclature Pseudocitrobacter limerickensis. The patient was colonized, rather than infected, and did not require antimicrobial treatment.

Large-scale characterization of hospital wastewater system microbiomes and clinical isolates from infected patients: profiling of multi-drug-resistant microbial species.

BACKGROUND: Hospital-acquired infections (HAIs) and infectious agents exhibiting antimicrobial resistance (AMR) are challenges globally. Environmental patient-facing wastewater apparatus including handwashing sinks, showers and toilets are increasingly identified as sources of infectious agents and AMR genes. AIM: To provide large-scale metagenomics analysis of wastewater systems in a large teaching hospital in the Republic of Ireland experiencing multi-drug-resistant HAI outbreaks. METHODS: Wastewater pipe sections (N=20) were removed immediately prior to refurbishment of a medical ward where HAIs had been endemic. These comprised toilet U-bends, and sink and shower drains. Following DNA extraction, each pipe section underwent metagenomic analysis. FINDINGS: Diverse taxonomic and resistome profiles were observed, with members of phyla Proteobacteria and Actinobacteria dominating (38.23 ± 5.68% and 15.78 ± 3.53%, respectively). Genomes of five clinical isolates were analysed. These AMR bacterial isolates were from patients >48 h post-admission to the ward. Genomic analysis determined that the isolates bore a high number of antimicrobial resistance genes (ARGs). CONCLUSION: Comparison of resistome profiles of isolates and wastewater metagenomes revealed high degrees of similarity, with many identical ARGs shared, suggesting probable acquisition post-admission. The highest numbers of ARGs observed were those encoding resistance to clinically significant and commonly used antibiotic classes. Average nucleotide identity analysis confirmed the presence of highly similar or identical genomes in clinical isolates and wastewater pipes. These unique large-scale analyses reinforce the need for regular cleaning and decontamination of patient-facing hospital wastewater pipes and effective infection control policies to prevent transmission of nosocomial infection and emergence of AMR within potential wastewater reservoirs.

Systematic Review of the Effect on Caries of Sugars Intake: Ten-Year Update.

An update of the systematic review of evidence on the association between amount of sugars intake and dental caries, as well as on the effect of restricting sugars intake to <10% and <5% energy (E) on caries, was conducted, almost 10 y since the review that informed the World Health Organization (WHO) Guideline on Sugars. The aim was to systematically review epidemiological data published from 2011 to 2020 on the amount of sugars consumption and levels of caries and to report the findings for adults and children. Data sources included MEDLINE, EMBASE, Cochrane Database, Cochrane Central Register of Controlled Trials, Latin American and Caribbean Health Sciences, China National Knowledge Infrastructure, Scopus, and Google Scholar. Eligible studies reported the amount of sugars and caries, measured as prevalence, incidence, or severity. The review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Risk of bias was assessed using the Office of Health Assessment and Translation tool. Vote counting and harvest plots provided the basis for evidence synthesis. From 488 new papers identified, 23 studies were eligible: 4 cohort, 1 case-controlled, 12 cross-sectional, and 6 ecological. Eleven of 15 studies in children and 6 of 8 studies in adults reported at least 1 positive association between sugars and caries. Six of 7 studies in children and 4 of 4 studies in adults, with data enabling comparison of caries levels with sugars intakes >10%E and <10%E, showed lower caries when sugars intake was <10%E. Amalgamating with original studies yielded 64 of 78 studies showing at least 1 positive association, 20 of 78 a null association, and 3 of 78 a negative association between sugars and caries. GRADE profiles of new and original cohort data confirmed "moderate-quality" evidence that caries is lower when sugars intake is <10%E. Furthermore, new cohort data upgraded the quality of evidence (from "very low" to "low") for lower caries when free sugars are <5%E. The findings support and strengthen original evidence underpinning the WHO recommendations for sugars.

In situ fluoride response of caries lesions with different mineral distributions at baseline.

The present in situ study investigated the fluoride response of caries lesions with similar mineral loss but two distinct mineral distributions (low- and high-'R', calculated as the ratio of mineral loss to lesion depth). Sixteen subjects wore eight gauze-covered enamel specimens with preformed lesions placed buccally on their mandibular partial dentures for periods up to 4 weeks. The participants brushed twice daily for 1 min with an 1,100 ppm F (as NaF) dentifrice. After 3 and 4 weeks, specimens were retrieved and analyzed microradiographically (TMR) and by quantitative light fluorescence (QLF). TMR results revealed that low- and high-R lesions showed opposite behaviors - low-R lesions further demineralized, whereas high-R lesions exhibited some remineralization. In comparison, lesion depth increased in low-R, but remained unchanged in high-R lesions; R decreased in both, but more in high-R lesions; mineral density at the lesion surface remained unchanged in low-R, but increased in high-R lesions. Differences in mineral loss between lesion types increased further between 3 and 4 weeks. QLF did not mirror TMR results as low-R lesions were found to remineralize, whereas high-R lesions remained unchanged. It is likely that low-R lesions differ from high-R lesions chemically and microstructurally; therefore rendering low-R lesion more susceptible to further dissolution. During lesion formation, low-R in contrast to high-R lesions may not lose all of the solubility-determining impurities such as magnesium and carbonate, which can reprecipitate again in different mineral phases within the lesion. In conclusion, mineral distribution at baseline directly impacts in situ lesion response to fluoride.

Erythropoietin elevates VO2,max but not voluntary wheel running in mice.

Voluntary activity is a complex trait, comprising both behavioral (motivation, reward) and anatomical/physiological (ability) elements. In the present study, oxygen transport was investigated as a possible limitation to further increases in running by four replicate lines of mice that have been selectively bred for high voluntary wheel running and have reached an apparent selection limit. To increase oxygen transport capacity, erythrocyte density was elevated by the administration of an erythropoietin (EPO) analogue. Mice were given two EPO injections, two days apart, at one of two dose levels (100 or 300 microg kg(-1)). Hemoglobin concentration ([Hb]), maximal aerobic capacity during forced treadmill exercise (VO2,max) and voluntary wheel running were measured. [Hb] did not differ between high runner (HR) and non-selected control (C) lines without EPO treatment. Both doses of EPO significantly (P<0.0001) increased [Hb] as compared with sham-injected animals, with no difference in [Hb] between the 100 microg kg(-1) and 300 microg kg(-1) dose levels (overall mean of 4.5 g dl(-1) increase). EPO treatment significantly increased VO2,max by approximately 5% in both the HR and C lines, with no dosexline type interaction. However, wheel running (revolutions per day) did not increase with EPO treatment in either the HR or C lines, and in fact significantly decreased at the higher dose in both line types. These results suggest that neither [Hb] per se nor VO2,max is limiting voluntary wheel running in the HR lines. Moreover, we hypothesize that the decrease in wheel running at the higher dose of EPO may reflect direct action on the reward pathway of the brain.

The effect of brushing time and dentifrice quantity on fluoride delivery in vivo and enamel surface microhardness in situ.

While the clinical anticaries efficacy of fluoride toothpaste is now without question, our understanding of the relation of fluoride efficacy to brushing time and dentifrice quantity is limited. The aim of this in situ study was to determine how differences in brushing time and dentifrice quantity influence (i) fluoride distribution immediately after brushing, (ii) clearance of fluoride in saliva, (iii) enamel fluoride uptake (EFU) and (iv) enamel strengthening, via the increase in surface microhardness. The study compared brushing times of 30, 45, 60, 120 and 180 s with 1.5 g of dentifrice containing 1,100 microg/g fluoride as sodium fluoride. In addition, 60 s of brushing with 0.5 g dentifrice was evaluated. A longer brushing time progressively reduced retention of dentifrice in the brush, thereby increasing the amount delivered into the mouth. A longer brushing time also increased fluoride concentrations in saliva for at least 2 h after the conclusion of brushing, showing that increased contact time promoted fluoride retention in the oral cavity. There was a statistically significant positive linear relationship between brushing time and both enamel strengthening and EFU. Compared to 0.5 g dentifrice, brushing with 1.5 g dentifrice more than doubled the fluoride recovered in saliva after brushing and increased EFU. In conclusion, the results of this preliminary, short-term usage study suggest for the first time that both brushing time and dentifrice quantity may be important determinants both of fluoride retention in the oral cavity and consequent enamel remineralization.

An unclassifiable cellular myofibroblastic proliferation with an unusual clinical presentation.

We present a case of a 50-year-old man with unusual extensive linear lesions on the right leg that had been present from the age of 2 years. As a child he had been treated with oral steroids under a working diagnosis of linear scleroderma. He went on to undergo multiple operations and skin-grafting procedures under the care of the plastic surgeons and presented to the dermatology department in 2004 because of itchy, scaly and painful lesions extending from the original area. Multiple biopsies had been taken, all showing similar histopathological features of a poorly differentiated dermal lesion composed of fibrohistiocytic cells arranged in a whorled pattern, similar to that seen in dermatofibroma. There was positive staining with vimentin and SMA, and negative staining with caldesmon, D33, CD34, S100 and factor 13a, indicating that the cell of origin was a myofibroblast. Clinically this extensive lesion does not fit the characteristics of a dermatofibroma. It also does not fit readily into any previously described fibrous tissue tumour condition, and, to our knowledge, is a unique case. The patient remains under close clinical observation given that there is no way of predicting the long-term prognosis, but to date no suspicious features have been seen.

Influence of fluoride availability of dentifrices on eroded enamel remineralization in situ.

Remineralization of eroded enamel by dentifrices containing similar sources/concentrations of fluoride was investigated in situ. Fifty-three subjects completed a double-blind crossover study with 3 randomly assigned dentifrice treatments: placebo (0 ppm F, PD); reference (1,450 ppm NaF, RD) and test (1,450 ppm NaF + 5% KNO(3), TD). Fluoride availability for each dentifrice was analyzed in vitro by standard tests (1-min fluoride release rate and enamel fluoride uptake). The subjects wore palatal appliances holding bovine enamel specimens previously eroded in vitro. Surface microhardness was determined before and after the in vitro erosive challenge, after in situ remineralization and after a second in vitro erosive challenge. ANOVA and pairwise comparisons were performed (alpha=0.05). TD was superior to RD in the fluoride release tests, but similar to RD in the enamel fluoride uptake test. The mean percent surface microhardness recovery was 21.9 (standard deviation 8.0) for PD, 28.6 (8.0) for RD and 36.0 (8.0) for TD. The mean percent relative erosion resistance change was -58.8 (12.7) for PD, -31.3 (12.7) for RD and -27.3 (12.6) for TD. Both fluoride-containing dentifrices provided superior remineralization (p<0.001) and erosion resistance (p<0.001) compared to PD. The percent surface microhardness recovery demonstrated by the TD was significantly greater than for the RD (p<0.001). There was no significant difference (p=0.073) between TD and RD in relative resistance to further erosive challenge. The results suggest that fluoride availability may be different in dentifrices with similar sources/concentrations of fluoride, providing different levels of remineralization of eroded enamel.

Systematic Review of Evidence Pertaining to Factors That Modify Risk of Early Childhood Caries.

INTRODUCTION: A systematic review of evidence on the impact of modifiable risk factors on early childhood caries (ECC) was conducted to inform recommendations in a World Health Organization manual on ECC prevention. OBJECTIVES: To systematically review published evidence pertaining to the effect of modifiable risk factors on ECC. METHODS: Twelve questions relating to infant feeding, diet, oral hygiene, and fluoride were addressed, as prioritized by a World Health Organization expert panel. Questions pertaining to the use of fluoride toothpaste were excluded due to its proven efficacy. The target population was children aged <72 mo. Data sources included Medline, Embase, CINAHL, and PubMed, and all human epidemiologic studies were included. The highest level of evidence was used for evidence synthesis and, where possible, meta-analysis. The review was conducted in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) statement, with evidence assessed via the GRADE method. RESULTS: Of the 13,831 papers identified, 627 were screened in duplicate; of these, 139 were included. The highest-level evidence indicated that breastfeeding ≤24 mo does not increase ECC risk but suggested that longer-duration breastfeeding increases risk (low-quality evidence). Low-quality evidence indicated increased risk associated with consumption of sugars in bottles. Only 1 study had data on the impact of sugars in complementary foods, which increased risk. Moderate-quality evidence showed a benefit of oral health education for caregivers (odds ratio, 0.39; 95% CI, 0.19 to 0.80, P = 0.009). Meta-analysis of data on the impact on ECC from living in a fluoridated area showed a significant effect (mean difference, -1.25; 95% CI, -1.24 to -0.36; P = 0.006). Limited moderate- and low-quality data indicated a benefit of fluoride exposure from salt and milk, respectively. CONCLUSION: The best available evidence indicates that breastfeeding up to 2 y of age does not increase ECC risk. Providing access to fluoridated water and educating caregivers are justified approaches to ECC prevention. Limiting sugars in bottles and complementary foods should be part of this education. KNOWLEDGE TRANSFER STATEMENT: This research is being used by the World Health Organization in developing a toolkit on the prevention and management of early childhood caries. The information will guide 1) governments in developing national oral health plans and 2) clinicians when providing preventive advice, including that regarding infant feeding practices. It will help ensure that advice is in line with current World Health Organization guidelines and the best available evidence.

Wholegrain cereals for coronary heart disease.

BACKGROUND: There is increasing evidence from observational studies that wholegrains can have a beneficial effect on risk factors for coronary heart disease (CHD). OBJECTIVES: The primary objective is to review the current evidence from randomised controlled trials (RCTs) that assess the relationship between the consumption of wholegrain foods and the effects on CHD mortality, morbidity and on risk factors for CHD, in participants previously diagnosed with CHD or with existing risk factors for CHD. SEARCH STRATEGY: We searched CENTRAL (Issue 4, 2005), MEDLINE (1966 to 2005), EMBASE (1980 to 2005), CINAHL (1982 to 2005), ProQuest Digital Dissertations (2004 to 2005). No language restrictions were applied. SELECTION CRITERIA: We selected randomised controlled trials that assessed the effects of wholegrain foods or diets containing wholegrains, over a minimum of 4 weeks, on CHD and risk factors. Participants included were adults with existing CHD or who had at least one risk factor for CHD, such as abnormal lipids, raised blood pressure or being overweight. DATA COLLECTION AND ANALYSIS: Two of our research team independently assessed trial quality and extracted data. Authors of the included studies were contacted for additional information where this was appropriate. MAIN RESULTS: Ten trials met the inclusion criteria. None of the studies found reported the effect of wholegrain diets on CHD mortality or CHD events or morbidity. All 10 included studies reported the effect of wholegrain foods or diets on risk factors for CHD. Studies ranged in duration from 4 to 8 weeks. In eight of the included studies, the wholegrain component was oats. Seven of the eight studies reported lower total and low density lipoproteins (LDL) cholesterol with oatmeal foods than control foods. When the studies were combined in a meta-analysis lower total cholesterol (-0.20 mmol/L, 95% confidence interval (CI) -0.31 to -0.10, P = 0.0001 ) and LDL cholesterol (0.18 mmol/L, 95% CI -0.28 to -0.09, P < 0.0001) were found with oatmeal foods. However, there is a lack of studies on other wholegrains or wholegrain diets. AUTHORS' CONCLUSIONS: Despite the consistency of effects seen in trials of wholegrain oats, the positive findings should be interpreted cautiously. Many of the trials identified were short term, of poor quality and had insufficient power. Most of the trials were funded by companies with commercial interests in wholegrains. There is a need for well-designed, adequately powered, longer term randomised controlled studies in this area. In particular there is a need for randomised controlled trials on wholegrain foods and diets other than oats.

Evaluation of a desensitizing test dentifrice using an in situ erosion remineralization model.

OBJECTIVE: To evaluate, in an in situ remineralization model, the ability of a low abrasion fluoride dentifrice containing potassium nitrate to enhance the remineralization of enamel that was previously subjected to an in vitro dietary erosion challenge. METHODOLOGY: Thirteen subjects completed a single-blind (to specimen analyst) crossover design study with four randomly assigned dentifrice treatments: placebo dentifrice (0 ppm F; PD); dose response control dentifrice (250 ppm F; DD); clinically tested fluoride dentifrice (1100 ppm F; FD); and test dentifrice (1150 ppm F + 5% KNO3; TD). Each subject wore a palatal appliance holding eight bovine enamel blocks that were previously exposed for 25 minutes to an in vitro erosive challenge with grapefruit juice. Surface microhardness (SMH) was determined prior to the erosive challenge (baseline), after the in vitro erosive challenge, after in situ remineralization, and after a second in vitro erosive challenge. Statistical analyses included ANOVA and pair-wise comparisons between treatments, testing at a 5% significance level. RESULTS: The mean percent SMH recovery (SD) was 20.4 (7.7)a for PD; 27.4 (5.9)b for DD; 29.5 (8.9)bc for FD; 33.4 (6.7)c for TD. The mean percent net erosion resistance (SD) was -57.7 (10.8)a for PD; -41.3 (11.6)b for DD; -28.7 (9.7)c for FD; -23.6 (7.3)c for TD. Different superscript letters following the means imply statistically significant differences between groups for each response. CONCLUSION: The test dentifrice was shown to significantly enhance the remineralization of enamel previously subjected to an erosion challenge.

Enhancement of metastatic potential by gamma-interferon.

Preincubation of murine colon 26 colon adenocarcinoma cells with gamma-interferon (IFN-gamma), but not alpha-interferon, produced a significant increase in experimental pulmonary metastases in syngeneic BALB/c and T-cell-deficient BALB/c nude mice. The enhancement was seen after as little as 1 h of exposure to 1 unit/ml of IFN-gamma and persisted for at least 72 h following removal of the cytokine. IFN-gamma exerted its effects by increasing the pulmonary retention of cells during the first 6 h following tumor cell injection. During this period all cells visualized in the lung were trapped in pulmonary capillaries. The enhancement was not due to modulations in class I major histocompatibility complex surface antigen expression; nor was it due to alterations in cell size, adhesion to components of the extracellular matrix in vitro, heterotypic or homotypic adhesion, sensitivity to lysis by activated peritoneal macrophages, osmotic fragility, enhancement of surface class II major histocompatibility complex antigen expression, or enhancement of intercellular adhesion molecule-1 (ICAM-1). Colon 26 was completely resistant to natural killer cell-mediated lysis in vitro, and IFN-gamma did not modulate the ability of colon 26 to form conjugates with isolated splenocytes. In vivo elimination of anti-asialo GM1 + cells increased pulmonary metastasis, and in such mice, there was no longer a difference in metastatic potential between control and IFN-gamma-treated cells. We conclude that low doses of IFN-gamma generated at the site of the tumor by host-infiltrating cells or during cytokine therapy could enhance the survival of tumor cells in the circulation and enhance their metastatic potential.

Effect of toothbrushing duration and dentifrice quantity on enamel remineralisation: An in situ randomized clinical trial.

OBJECTIVES: The influence of toothbrushing duration and dentifrice quantity on fluoride efficacy against dental caries is poorly understood. This study investigated effects of these two oral hygiene factors on enamel remineralisation (measured as surface microhardness recovery [SMHR]), enamel fluoride uptake (EFU), and net acid resistance (NAR) post-remineralisation in a randomized clinical study using an in situ caries model. METHODS: Subjects (n=63) wore their partial dentures holding partially demineralised human enamel specimens and brushed twice-daily for two weeks, following each of five regimens: brushing for 120 or 45s with 1.5g of 1150ppm F (as NaF) dentifrice; for 120 or 45s with 0.5g of this dentifrice; and for 120s with 1.5g of 250ppm F (NaF) dentifrice. RESULTS: Comparing brushing for 120s against brushing for 45s, SMHR and EFU increased by 20.0% and 26.9% respectively when 1.5g dentifrice was used; and by 22.8% and 19.9% respectively when 0.5g dentifrice was used. Comparing brushing with 1.5g against brushing with 0.5g dentifrice, SMHR and EFU increased by 35.3% and 51.3% respectively when brushing for 120s, and by 38.4% and 43.0% respectively when brushing for 45s. Increasing brushing duration and dentifrice quantity also increased the NAR value. The effects of these two oral hygiene factors on SMHR, EFU, and NAR were statistically significant (p<0.05 in all cases). CONCLUSION: Brushing duration and dentifrice quantity have the potential to influence the anti-caries effectiveness of fluoride dentifrices. Study NCT01563172 on ClinicalTrials.gov. CLINICAL SIGNIFICANCE: The effect of two key oral hygiene regimen factors - toothbrushing duration and dentifrice quantity - on fluoride's anticaries effectiveness is unclear. This 2-week home-use in situ remineralisation clinical study showed both these factors can influence fluoride bioactivity, and so can potentially affect fluoride's ability to protect against caries.

Hyperacute lung rejection in the pig-to-human model 4: evidence for complement and antibody independent mechanisms.

BACKGROUND: We assessed whether the combination of complement regulation and depletion of xenoreactive antibodies improves the outcome of pulmonary xenografts compared with either strategy alone. METHODS: Lungs from pigs heterozygous (hDAF(+/-)) or homozygous (hDAF(+/+)) for the human decay accelerating factor transgene (hDAF) or their nontransgenic litter mates (hDAF(-/-)) were perfused with heparinized whole human blood. In additional groups, xenoreactive natural antibodies (XNA) were depleted by pig lung perfusion (hDAF(-/-)/AbAbs, hDAF(+/-)/AbAbs) before the experiment. This combined approach was augmented by adding soluble complement receptor 1 (sCR1) to the perfusate in one further group (hDAF(+/-)/AbAbs/sCR1). RESULTS: HDAF(-/-) lungs perfused with unmodified human blood were rejected after 32.5 min (interquartile range, IQR 5 to 210). HDAF(+/-) lungs survived for 90 min (IQR 10 to 161, P = 0.54). Both groups showed a rapid rise in pulmonary vascular resistance (PVR), which is a characteristic feature of hyperacute rejection (HAR). This phenomenon was blunted in the hDAF(+/+) group, although survival (48 min, IQR 14 to 111) was not further prolonged. Antibody depletion (AbAbs) led to a significant increase in survival time (hDAF(-/-)/AbAbs: 315 min, IQR 230 to 427; hDAF(+/-)/AbAbs: 375 min, IQR 154 to 575), reduced PVR and less complement production. Addition of sCR1 reduced complement elaboration but did not further improve survival (200 min, IQR 128 to 580) and surprisingly tended to increase PVR. CONCLUSIONS: Depletion of xenoreactive antibodies is more effective than membrane-bound complement regulation to blunt hyperacute rejection of pulmonary xenografts, but even the combined approach including soluble-phase complement inhibition is not sufficient to reliably prevent organ failure within hours. It therefore seems likely that other factors independent of antibody and complement contribute to HAR in this model.

Dose-response effect of fluoride dentifrice on remineralisation and further demineralisation of erosive lesions: A randomised in situ clinical study.

OBJECTIVE: The objective was to evaluate the ability of fluoride in a conventional, non-specialised sodium fluoride-silica dentifrice to promote tooth remineralisation and enamel fluoride uptake (EFU), and assess the resistance of the newly formed mineral to attack by dietary acid, across the concentration range used in mass-market dentifrices. METHODS: Subjects wore a palatal appliance containing eight polished bovine enamel specimens, each including an early erosive lesion. In a randomised full-crossover sequence, 62 healthy subjects were treated with dentifrices containing four different fluoride concentrations: no fluoride; 250ppm, 1150ppm and 1426ppm fluoride. At each treatment visit, under supervision, subjects brushed with 1.5g dentifrice and rinsed once while wearing the appliance; the appliance was removed after a 4-h remineralisation period and effects on the enamel specimens determined. The primary efficacy variable was surface microhardness recovery (SMHR); others included EFU, relative erosion resistance (RER) and comparative erosion resistance. RESULTS: Highly significant linear and, with the exception of SMHR, quadratic dose-response relationships were observed between all efficacy variables and fluoride concentration. For SMHR, EFU and RER, values for the different fluoride concentrations were statistically resolved from one another, with the exception of the two highest fluoride concentrations. The degree of remineralisation and the acid resistance of enamel after treatment were closely related to EFU. CONCLUSION: After a single brushing, conventional non-specialised sodium fluoride-silica dentifrices promoted remineralisation of early enamel lesions, and imparted increased acid-resistance to the enamel surface, in a dose-dependent manner at least up to 1500ppm fluoride. CLINICAL SIGNIFICANCE: Enamel erosive tissue loss is an increasing concern, associated with modern diets. This study demonstrated that sodium fluoride, in a conventional non-specialised dentifrice formulation, can promote repair of the earliest stages of enamel erosion after a single application, in a dose-dependent fashion across the fluoride concentration range used in mass-market dentifrices. This study is registered in the GlaxoSmithKline Study Register (ID RH01299), available at: www.gsk-clinicalstudyregister.com/study/RH01299.

Elemental analysis of femoral bone from patients with fractured neck of femur or osteoarthrosis.

The elemental composition of bone has been determined by inductively coupled atomic emission and mass spectrometry to test the hypothesis that changes in major or minor elemental concentrations may contribute to the risk of fracture. Femoral bone was obtained from patients at operation for the treatment of fracture and compared with that of patients with osteoarthrosis and a necropsy control group. The data suggest that there are no major differences in bone elemental composition in patients with fractures compared with the control group. Bone adjacent to joints with osteoarthrosis tends to be less mineralized (per unit trabecular bone volume) than control bone and bone from fracture patients, and has significantly lower concentrations of boron, lead and, zinc. These observations may reflect the more rapid turnover of bone close to the arthritic joint.

The identification of antigenic determinants by a coupled inhibition-agar diffusion method.

The determination of the chemical nature of immunodeterminant groups of carbohydrate antigens has been achieved by a micro method coupling inhibition and double diffusion in agar. This method has been tested with antigens which react with anti-lactose, anti-galactose, anti-N-acetyl-glucosamine and antirhamnose antibodies. The analysis can be performed with as little as 10 micrograms of inhibitor, 0.2 microgram of antigen and 10 micrograms of antibody. The procedure has also been used for the identification of the determinant groups of 2 antigens with a phosphoglycan structure. The determinants of these antigens have been found to be N-acetyl-beta-glucosamine 1-phosphate and beta-glucose 1-phosphate. The glycosyl 1-phosphate units are novel types of antigenic determinants and antigens with such determinants should be useful for investigating the interactions of antigens with homologous antibodies. The specificity of monoclonal antibodies directed at an O-antigen has been determined by use of the coupled method.

Radiation pneumonitis in patients treated for breast cancer.

An analysis of 201 breast cancer patients having post-operative radiotherapy to the chest wall between January 1981 and May 1983 has identified those patients with chest symptoms following radiotherapy and these have been critically assessed with regard to the possibility of radiation pneumonitis being their cause. The inner contour of the anterior chest wall has been reconstructed on the radiation plan and the area of lung irradiated to a significant level in the mid-plane of the tangential fields determined. The incidence and severity of pneumonitis has been shown to rise exponentially with increase in the irradiated volume. A method of measuring the thickness of the chest wall using the simulator has been devised so that this information may be incorporated into the planning process in order to reduce the area of lung at risk.

Active minimisation of radiation scatter during breast radiotherapy: management implications for young patients with good-prognosis primary neoplasms.

BACKGROUND AND PURPOSE: Radiotherapy is used to reverse or prevent local tumour growth but is also a carcinogen in its own right. A recent audit of post-radiotherapy second malignancies in this institution revealed a striking preponderance of tumours originating near the outside edge of the treatment field. Since this finding suggests the existence of a critical subtherapeutic dose range predisposing to tumourigenesis, we attempted to define and reduce this radiation scatter dose. MATERIALS AND METHODS: We undertook a dosimetric review of 6 MV scatter from a linear accelerator in sites matching the putative tumourigenic region, and then extended this analysis to patients and tissue phantoms. RESULTS: A wide range of radiation scatter doses was confirmed-for example, doses 3 cm from the field edge varied from 1.7 to 22% of the therapeutic dose depending upon the field parameters. Scatter doses were then assessed in a sample of eight patients undergoing standard breast radiotherapy. Contralateral breast sites 4-12 cm from the midline received 4-10% of the therapeutic dose, or 200-500 cGy for a 50 Gy treatment, approximating historical estimates of the tumourigenic range. The deep component of this scatter dose from medial field breast irradiation was reduced 19% simply by replacing the 15 degrees medial tangential field wedge with a 30 degrees lateral wedge. Other manoeuvres which reduced contralateral breast dose by up to 46% included making the posterior field edges co-planar and shielding the breast during medial field irradiation. CONCLUSIONS: These results suggest that the risk of radiogenic second malignancies could be significantly decreased by careful attention to the treatment details. Greater awareness of these measures may prove particularly relevant to the conservative management of young patients with good-prognosis breast neoplasms such as ductal carcinoma in situ.

Computer assisted selection and assessment of antibodies in the diagnosis of lymphomas.

With increasing numbers of reagents the problem of selecting appropriate antibodies to solve problems in the diagnosis of lymphoma is becoming more complex. One approach is to use a computer program to optimise the selection process. Such a program was devised, incorporating data from an extensive literature search. When presented with a differential diagnosis it selects the most appropriate antibody panel and when given the results evaluates the relative likelihood of each possible diagnosis. In a retrospective study 81% of the tests used had been non-discriminatory, but using the results of the remaining 19% of the tests, the computer was able to select the "correct" diagnosis with a high degree of certainty. The development and use of this system illustrated several problems in the application of computer assisted diagnostic techniques in histopathology. These problems include incomplete data and lack of understanding of the process of histopathological diagnosis.