In vitro evaluation of different protective techniques to reduce titanium particle contamination during implantoplasty.

OBJECTIVES: Our aim is to study titanium remains in a bone model during standardized implantoplasty under different isolation and protective modalities. MATERIAL AND METHODS: Forty implants were placed in artificial spongy bone blocks mimicking a horizontal bone loss and implant neck protrusion of 5 mm. Samples were randomly divided into four groups (n = 10), which were treated as follows: rubber dam (A), a dental adhesive paste (B), bone wax (C), and an unprotected positive control (D). Implantoplasty was performed using carbide and diamond burs under strict water cooling and standardized suction. After removal of the respective isolation materials, the bone blocks were thoroughly rinsed with tap water for 3 min and titanium chips were collected using a filter integrated in the model. The filter paper was removed and dissolved in 37% hydrochloric acid for 2 h at 120 °C and the titanium remnants were quantified using atomic absorption spectrometry. RESULTS: None of the test groups were able to completely prevent titanium particle contamination. Rubber dam (691 ± 249 µg) and bone wax (516 ± 157 µg) were found to be significantly more protective than the positive control (2313 ± 747 µg) (p < 0.001) with respect to the amount of titanium particles that remained in the bone model after implantoplasty. The adhesive paste group (1863.5 ± 538 µg) was not significantly different from the positive control (p = 0.19). CONCLUSIONS: Despite some limitations of the present study, titanium particles resulting from a standardized implantoplasty can be assumed to be significantly reduced when the tissues/bone were protected with rubber dam and bone wax, or a combination, depending on individual accessibility. CLINICAL RELEVANCE: Tissue protective measures to reduce or avoid particle contamination during implantoplasty is possible and should be considered and further clinically assessed to avoid iatrogenic inflammatory reactions.

The impact of an epilepsy nurse competency framework on the costs of supporting adults with epilepsy and intellectual disability: findings from the EpAID study.

BACKGROUND: The development of a nurse-led approach to managing epilepsy in adults with an intellectual disability (ID) offers the potential of improved outcomes and lower costs of care. We undertook a cluster randomised trial to assess the impact on costs and outcomes of the provision of ID nurses working to a designated epilepsy nurse competency framework. Here, we report the impact of the intervention on costs. METHOD: Across the United Kingdom, eight sites randomly allocated to the intervention recruited 184 participants and nine sites allocated to treatment as usual recruited 128 participants. Cost and outcome data were collected mainly by telephone interview at baseline and after 6 months. Total costs at 6 months were compared from the perspective of health and social services and society, with adjustments for pre-specified participant and cluster characteristics at baseline including costs. Missing data were imputed using multiple imputation. Uncertainty was quantified by bootstrapping. RESULTS: The intervention was associated with lower per participant costs from a health and social services perspective of -£357 (2014/2015 GBP) (95% confidence interval -£986, £294) and from a societal perspective of -£631 (95% confidence interval -£1473, £181). Results were not sensitive to the exclusion of accommodation costs. CONCLUSIONS: Our findings suggest that the competency framework is unlikely to increase the cost of caring for people with epilepsy and ID and may reduce costs.

Promoting breastfeeding in child care through state regulation.

Policies supporting breastfeeding vary by state, but little is known about the geographical aspects of this variation. This study describes state breastfeeding licensing and administrative regulations targeting child care settings, compares regulations with national standards, and examines the spatial patterning and clustering of these regulations throughout the United States (US). We compared regulations for child care centers (centers) and family child care homes (homes) with national standards for: (1) general breastfeeding support; (2) designated place for breastfeeding; (3) no solids before infants are four months of age; and (4) no formula for breastfed infants without parent permission. We scored state regulations as 0 = standard not addressed, 1 = standard partially addressed, and 2 = standard fully addressed. We considered each regulation individually, and also summed scores to provide an overall rating of regulations by state. We mapped regulations using geographic information systems technology, and explored overall and local spatial autocorrelation using global and local variants of Moran's I. Five states had regulations for centers and two for homes that addressed all four standards. Mean regulation scores were 0.35, 0.20, 0.98, 0.74 for centers, and 0.17, 0.15, 0.79, 0.58 for homes. Local Moran's I revealed that New York and Pennsylvania had substantially stronger regulations than their adjacent states, while Florida had weaker regulations than its neighbors. Overall, few states had regulations that met breastfeeding standards. We identified some patterns of spatial correlation, suggesting avenues for future research to better understand distributions of regulations across the US.

Abatacept modulates proinflammatory macrophage responses upon cytokine-activated T cell and Toll-like receptor ligand stimulation.

OBJECTIVES: We investigated whether Abatacept might reduce proinflammatory cytokine production by macrophages upon contact with cytokine activated T cells and/or stimulation with TLR ligands. METHODS: Macrophages and cytokine stimulated T cells (Tck) were added together in the presence of Abatacept or a control Ig, with or without TLR ligands. The production of cytokines was determined by luminex. RESULTS: Abatacept reduced Tck-induced production of TNFa by macrophages. Tck and TLR ligands synergistically induced the production of proinflammatory cytokines by macrophages, especially IL-12p70. The production of IL-12p70 coincided with the production of IFNg, which were both reduced in the presence of Abatacept. CONCLUSIONS: Tck induce the production of TNFa by macrophages and facilitate the highly increased production of proinflammatory cytokines in the presence of TLR ligands. Abatacept was shown to potently suppress these pathways suggesting that its role may extend beyond antigen specific T cell mediated effector function.

2-Week wait referrals in suspected skin cancer: does an instructional module for general practitioners improve diagnostic accuracy?

The two-week wait (2WW) scheme in the United Kingdom for suspected skin cancer has been criticised for having low pick up rates, with a high proportion of clinically benign lesions being referred as suspicious. We studied the referral patterns of skin cancer to our hospital under the 2WW initiative, and aimed to quantify the effect of a targeted continuing medical education (CME) module on improving diagnostic accuracy. All referrals to our hospital (dermatology and plastic surgery) under the 2WW rule were audited between July and September 2006. A targeted CME module was sent to GPs describing and illustrating common lesions. After 11 months, all 2WW referrals were prospectively studied between August and October 2007. The main outcome measure was the percentage of correctly referred squamous cell carcinomas (SCCs) and melanomas. 237 referrals were made between July and August 2006, and 223 referrals between August and October 2007. The proportion of appropriately referred skin cancers (SCCs and melanomas) was 23.2% before CME, and 20.6% after CME. There were no differences in pick up rates before and after the CME amongst suspected SCCs (21.1% vs. 29.7%) or melanomas (24.6% vs. 15.1% respectively). Referrals to Plastic Surgery were more likely to be confirmed histologically as melanomas or SCCs (23.6% and 33.7% respectively) than those made to Dermatology (17.5% and 15.3% respectively). The proportion of correctly suspected skin malignancies under the 2WW initiative remains low despite education. A targeted CME module sent to GPs fails to improve pick up rates. There is a need for continuing dermatology training amongst referring physicians.

Identification of pathological RA endotypes using blood-based biomarkers reflecting tissue metabolism. A retrospective and explorative analysis of two phase III RA studies.

There is an increasing demand for accurate endotyping of patients according to their pathogenesis to allow more targeted treatment. We explore a combination of blood-based joint tissue metabolites (neoepitopes) to enable patient clustering through distinct disease profiles. We analysed data from two RA studies (LITHE (N = 574, follow-up 24 and 52 weeks), OSKIRA-1 (N = 131, follow-up 24 weeks)). Two osteoarthritis (OA) studies (SMC01 (N = 447), SMC02 (N = 81)) were included as non-RA comparators. Specific tissue-derived neoepitopes measured at baseline, included: C2M (cartilage degradation); CTX-I and PINP (bone turnover); C1M and C3M (interstitial matrix degradation); CRPM (CRP metabolite) and VICM (macrophage activity). Clustering was performed to identify putative endotypes. We identified five clusters (A-E). Clusters A and B were characterized by generally higher levels of biomarkers than other clusters, except VICM which was significantly higher in cluster B than in cluster A (p<0.001). Biomarker levels in Cluster C were all close to the median, whilst Cluster D was characterised by low levels of all biomarkers. Cluster E also had low levels of most biomarkers, but with significantly higher levels of CTX-I compared to cluster D. There was a significant difference in ΔSHP score observed at 52 weeks (p<0.05). We describe putative RA endotypes based on biomarkers reflecting joint tissue metabolism. These endotypes differ in their underlining pathogenesis, and may in the future have utility for patient treatment selection.

The mitogenome of Hydropsyche pellucidula (Hydropsychidae): first gene arrangement in the insect order Trichoptera.

We describe the mitochondrial genome of Hydropsyche pellucidula Curtis 1834, which is first described for the suborder Annulipalpia and the first in the order Trichoptera to show a non-canonical gene order. The mitogenome was obtained by de novo assembly of shotgun sequenced total genomic DNA using Illumina Miseq technology, which produced an average coverage of 115× and a minimum coverage of 48×. The mitochondrial genome includes 13 protein-coding genes, 2 rRNAs and 22 tRNAs. The genome is characterized by a rearrangement in the relative position of protein-coding and ribosomal genes. This mitogenome sequence will be useful for studying the family Hydropsychidae, which is commonly used for freshwater pollution biomonitoring.

Use of polarised equine endothelial cell cultures and an in vitro thrombosis model for potential characterisation of EHV-1 strain variation.

Equine herpesvirus-1 (EHV-1) is responsible for respiratory disease and abortion in pregnant mares. Some high virulence isolates of EHV-1 also cause neurological disease. The pathogenesis of both abortion and neurological disease relates in part, to thrombus formation occurring in the pregnant uterus and central nervous system. The differences in disease outcome may relate to differing abilities of high and low virulence EHV-1 isolates to cause cell-associated viraemia, infect endothelial cells and cause thrombosis at sites distant from the respiratory tract. This study attempted to identify in vitro assays, which could be used to characterise the interaction between these isolates, equine endothelial cells and clotting factors. No significant difference was found between the growth kinetics of high and low virulence isolates of EHV-1 in polarised endothelial cells. For both isolates, virus was released preferentially from the apical surface of the polarised cells. The functional effects of viral infection on endothelial cells, with reference to virally-induced thrombosis were then investigated. Endothelial cells were grown on microcarrier beads, infected with EHV-1 and assayed for procoagulant activity. No significant difference in clotting time was observed between mock and EHV-1 infected endothelial cells in microcarrier cultures. Thus the degree of thrombosis may reflect a more complex interaction between endothelial cells, circulating leucocytes and other factors in the microenvironment.

Hand surgery on patients who are "high risk" for blood-borne viruses.

There is a risk of transmission of blood-borne viruses (BBV) to health-care workers when performing hand surgery on intravenous drug abusers and other patients known to have BBV. This review summarises methods and procedures that may be employed to help reduce this risk to a minimum. High-risk patients should be identified early and a non-invasive procedure considered. Only experienced staff should scrub and appropriate clothing should be worn. Sharp instrument use should be kept to a minimum and only instrument retraction and suturing should be employed. When possible, wounds should be closed with staples, glue or absorbable sutures. Appropriate steps must be taken to reduce the risk of injuries from sharp bone ends, K-wires and splash exposure during irrigation.

Effects of bilateral breast reduction on anxiety and depression: results of a prospective randomised trial.

We assessed the effects of bilateral breast reduction on anxiety and depression in women with mammary hypertrophy (macromastia). Seventy-three consecutive women referred for consideration for breast reduction were recruited. They were randomised to have either early operation (within six weeks of initial assessment) or delayed operation (within six months of recruitment). The Hospital Anxiety and Depression Score was given before randomisation and four months later. All 73 patients completed the study. The mean (SD) age was 39 (12) years. The groups were matched for age, smoking, social class, and educational achievement. There were highly significant improvements (p<0.001) in symptoms of anxiety and depression. Reduction mammaplasty significantly improved symptoms of clinical depression in women with macromastia.

Lessons from genome skimming of arthropod-preserving ethanol.

Field-collected specimens of invertebrates are regularly killed and preserved in ethanol, prior to DNA extraction from the specimens, while the ethanol fraction is usually discarded. However, DNA may be released from the specimens into the ethanol, which can potentially be exploited to study species diversity in the sample without the need for DNA extraction from tissue. We used shallow shotgun sequencing of the total DNA to characterize the preservative ethanol from two pools of insects (from a freshwater habitat and terrestrial habitat) to evaluate the efficiency of DNA transfer from the specimens to the ethanol. In parallel, the specimens themselves were subjected to bulk DNA extraction and shotgun sequencing, followed by assembly of mitochondrial genomes for 39 of 40 species in the two pools. Shotgun sequencing from the ethanol fraction and read-matching to the mitogenomes detected ~40% of the arthropod species in the ethanol, confirming the transfer of DNA whose quantity was correlated to the biomass of specimens. The comparison of diversity profiles of microbiota in specimen and ethanol samples showed that 'closed association' (internal tissue) bacterial species tend to be more abundant in DNA extracted from the specimens, while 'open association' symbionts were enriched in the preservative fluid. The vomiting reflex of many insects also ensures that gut content is released into the ethanol, which provides easy access to DNA from prey items. Shotgun sequencing of DNA from preservative ethanol provides novel opportunities for characterizing the functional or ecological components of an ecosystem and their trophic interactions.

A distinct subset of chemokines dominates the mucosal chemokine response in inflammatory bowel disease.

BACKGROUND: Inflammatory bowel disease (IBD) is characterised by intense mucosal recruitment of activated leukocytes. Chemokines determine inflammatory leukocyte recruitment and retention. AIM: To compare expression of the entire chemokine family within colonic mucosa from IBD patients and uninflamed controls. METHODS: A microarray of cDNAs, representing every member of this superfamily and their cognate receptors, was hybridised with probes derived from colonoscopic biopsies. RESULTS: A distinct subset of chemokines, consisting of CXCLs 1-3 and 8 and CCL20, was upregulated in active colonic IBD, compared with uninflamed areas or tissue from controls. Increased expression of their cognate receptors, CXCR1, CXCR2 and CCR6, was confirmed by quantitative PCR and immunohistochemistry. An identical chemokine response was induced in Caco-2 cells by stimulation with interleukin (IL)-1beta, but not tumour necrosis factor-alpha (TNF-alpha). By contrast, IL-1beta and TNF-alpha were synergistic in an HT29 cell line and primary keratinocytes. CONCLUSIONS: IL-1beta and TNF-alpha appear to be the pivotal mediators of a previously unidentified coordinated epithelial chemokine response that dominates the mucosal chemokine environment in inflamed IBD tissue.

A simple technique for harvesting lymphocytes cultured in Terasaki plates.

A simple method has been developed for harvesting lymphocytes from Terasaki microplates based on a culture technique where the plates are inverted and the cells grown on the hanging meniscus of the medium in each well. Sixty individual filter discs were prepared in wells in a polycarbonate harvesting plate. A dry Terasaki plate was used to cut these filters with the harvester acting as a die. The inverted culture plate was then lowered onto the harvester to allow the cells on the meniscus from each well to be absorbed on the appropriate filter disc. The culture plate was then discarded and the cells on the filters washed in the harvester. The wash solutions were removed by suction through holes below each filter. The time taken to harvest the cultures from 60 wells of a plate was 3--5 min.

Comparison of liquid and dried blood for neonatal hemoglobinopathy screening: laboratory and programmatic issues.

OBJECTIVES: To compare laboratory and programmatic issues in neonatal hemoglobin screening in two systems using either liquid cord blood or heel puncture blood dried on filter paper (DB) to determine the accuracy of hemoglobin phenotype; the collection rate of cord blood versus DB; and the types of and reasons for errors. METHODS: Cord blood samples for 6904 newborns were analyzed by electrophoresis in a large hospital laboratory. DB samples on the same cohort were analyzed by isoelectric focusing in a state public health laboratory. RESULTS: Interlaboratory concordance was 99.4% for 6904 matched specimen pairs, which included 27 disease and 596 carrier phenotypes. In 42 pairs, discordances for potential disease phenotypes occurred with cord blood samples. Errors involving carrier phenotypes occurred in 15 cord blood samples and 14 DB samples. Inconclusive results requiring repeat testing occurred more often in the cord blood testing system (92) than in the DB system (23). Clerical transcriptions and limitations of the techniques accounted for most laboratory errors. Noncompliance in sample collection occurred more frequently with cord blood (181) than DB (86). CONCLUSIONS: Both systems are subject to errors, but are equally reliable for neonatal hemoglobinopathy screening.

Choriocarcinoma of the gallbladder: treated with cisplatin-based chemotherapy.

A case of non-gestational choriocarcinoma, primary in the gallbladder, is described. Pathology showed a mixture of adenocarcinoma and choriocarcinoma. A Medline search for the last 10 years has shown no similar cases reported. The use of cisplatin-based chemotherapy to treat non-gestational choriocarcinoma has also not been described. This patient showed a rapidly progressive disease as described in other reported cases of non-gestational choriocarcinoma. However, cisplatin-based chemotherapy, in this patient, produced a partial response defined as significantly decreased beta-HCG titers (more than 50%), and with stable appearance or slightly improvement of hepatic metastasis and survival for 1 yr.

A comparative study of silicone net dressing and paraffin gauze dressing in skin-grafted sites.

This prospective randomized study has compared paraffin gauze dressing (n = 19) with silicone net dressing (Mepitel, n = 19) applied as the first layer to newly grafted burn wounds. At the first postoperative dressing visual analogue pain scores were greater in the paraffin gauze group (mean 4.4) than in the silicone net group (mean 1.4, P < 0.01). All patients in the paraffin gauze group experienced some degree of pain on dressing removal, whereas 53 per cent of patients in the silicone net group experienced no pain. Overall graft take was similar in both groups, (silicone net mean 95.7 per cent; paraffin gauze mean 94.3 per cent). Dressings were harder to remove in the paraffin gauze group as assessed by a simple scoring system (P < 0.001). In conclusion silicone net dressing confers advantages over conventional paraffin gauze, especially in reducing patient discomfort during dressing changes.

Is there still a place for comfort care in severe burns.

Successive improvements in burn care have steadily increased the survivability of many major burn injuries, however for some patients with the most severe injuries comfort care rather than active resuscitation has been seen as the correct course of action. A survey of UK burn unit directors by postal questionnaire sought details of current practice regarding comfort care, the factors involved in the decision making process and their response to eight hypothetical case histories. An 84% response to the survey showed that units would, on average, actively resuscitate thirty-seven patients a year and administer comfort care three times per year. Opinion was often divided regarding the decision to resuscitate in the cases presented.

Free tissue transfer in the management of burns.

Although the majority of burn wounds undergoing surgical treatment require only excision with split-skin grafting, the introduction of free microvascular tissue transfer has allowed for the preservation of otherwise unsalvageable deep burn injuries and the resurfacing of burn scars in areas with no available local tissue. A total of 1699 patients with burn injuries were admitted to the Burns Unit in Newcastle upon Tyne in the 5 years 1989-1993. During this period 604 patients (35.5 per cent) required surgical treatment of their burns. Of these patients 582 (96.4 per cent) underwent excision of their burns with split-skin grafting, 13 (2.1 per cent) of the patients required local flap cover and nine patients (1.5 per cent) had free tissue transfer. Free flap loss in this study was 22 per cent in burns patients as compared to only 3 per cent in patients undergoing microsurgical reconstruction for other reasons.

Temperature profiles during resuscitation predict survival following burns complicated by smoke inhalation injury.

Temperature and resuscitation profiles of 15 non-survivors were compared with matched survivors of major burns. All patients were intubated and ventilated for smoke inhalation injury, survived more than 3 days postburn and had a cutaneous burn greater than 15 per cent of the body surface area (mean 32.3 +/- 11.0 per cent SD). Cases were matched for similar ages (within 10 years) and total body surface area burn (within 10 per cent). The rate of core temperature rise following admission to the burn unit was significantly greater in survivors (mean 0.46 +/0 0.18 degree C/h) compared with matched non-survivors (mean 0.30 +/- 0.15 degrees C/h; p < 0.01). Core temperature increased at a rate of 0.27 degrees C/h or greater in all survivors, whereas 7 non-survivors raised their core temperature at a rate less than this. The rate of skin temperature rise was also significantly greater in the survivors (mean 1.35 +/- 0.91 degrees C/h) compared with matched non-survivors (mean 0.63 +/- 0.43 degrees C/h, p < 0.01). In 13/15 survivors, the skin temperature increased at a rate of 0.6 degree C/h or greater, whereas in 8/15 non-survivors skin temperature increased at a rate less than this. There was a negative relationship between initial core temperature and delay from time of burn to admission to the burns unit in non-survivors (correlation coefficient = -0.92; p < 0.01), whereas there was no effect of delay in the survivors. These findings suggest that patients with a high mortality probability can be detected early in their clinical course by means of temperature profiles.

Pectoralis major "trapdoor" flap for silicone breast implant medial knuckle deformities.

Loss of breast parenchyma through surgery and physiologic involution can lead to problems of subglandular silicone breast implant palpability and even contour irregularities. This can give rise to patient concern and detracts from the aesthetics of the breast augmentation, particularly when it occurs medially. We present a simple solution to this problem on the medial side of the breast in the form of a small segmental medially based pectoralis major "trapdoor" flap that augments the implant soft-tissue cover intracapsularly, at the site where it is deficient. The technique, which has been used with success in five patients over 3 years, is described.