Enhanced release of calcium phosphate additives from bioresorbable orthopaedic devices using irradiation technology is non-beneficial in a rabbit model: An animal study.

OBJECTIVES: Bioresorbable orthopaedic devices with calcium phosphate (CaP) fillers are commercially available on the assumption that increased calcium (Ca) locally drives new bone formation, but the clinical benefits are unknown. Electron beam (EB) irradiation of polymer devices has been shown to enhance the release of Ca. The aims of this study were to: 1) establish the biological safety of EB surface-modified bioresorbable devices; 2) test the release kinetics of CaP from a polymer device; and 3) establish any subsequent beneficial effects on bone repair in vivo. METHODS: ActivaScrew Interference (Bioretec Ltd, Tampere, Finland) and poly(L-lactide-co-glycolide) (PLGA) orthopaedic screws containing 10 wt% ß-tricalcium phosphate (ß-TCP) underwent EB treatment. In vitro degradation over 36 weeks was investigated by recording mass loss, pH change, and Ca release. Implant performance was investigated in vivo over 36 weeks using a lapine femoral condyle model. Bone growth and osteoclast activity were assessed by histology and enzyme histochemistry. RESULTS: Calcium release doubled in the EB-treated group before returning to a level seen in untreated samples at 28 weeks. Extensive bone growth was observed around the perimeter of all implant types, along with limited osteoclastic activity. No statistically significant differences between comparative groups was identified. CONCLUSION: The higher than normal dose of EB used for surface modification did not adversely affect tissue response around implants in vivo. Surprisingly, incorporation of ß-TCP and the subsequent accelerated release of Ca had no significant effect on in vivo implant performance, calling into question the clinical evidence base for these commercially available devices.Cite this article: I. Palmer, S. A. Clarke, F. J Buchanan. Enhanced release of calcium phosphate additives from bioresorbable orthopaedic devices using irradiation technology is non-beneficial in a rabbit model: An animal study. Bone Joint Res 2019;8:266-274. DOI: 10.1302/2046-3758.86.BJR-2018-0224.R2.

[Management of vaginal infection following failure of a probabilistic treatment: is the vaginal swab really useful?]. / Prise en charge des infections vaginales après échec d'un traitement probabiliste : le prélèvement vaginal est-il réellement utile ?

OBJECTIVE: The aim of this observational national multi-centre study was to describe medical care of vaginal infections resisting a primary probabilistic treatment. PATIENTS AND METHODS: Two hundred and seventy female patients were included during a 9-month period (from 2013, March 20th to 2013, December 7th) by 155 gynaecologists located throughout France. RESULTS: All patients were presenting a vulvo-vaginitis episode which started about three weeks ago and which was characterized by leucorrhea (93 % cases), itching (88 % cases) and/or vulvar and/or vaginal irritation (88 % cases). In most cases, this episode was previously treated by a short course of an azole antifungal medication. This treatment was initiated by the patient herself without any doctor's prescription in six out of 10 cases and had no influence on the evolution of the original clinical symptoms. Second line treatments included azole antifungal medications (56 % cases), local fixed combinations (antifungal agent and bactericidal antibiotic) (29 %), metronidazole (9 %), oral antibiotics (7.4 %). At the end of the treatment, 85 % patients recovered from vaginitis symptoms. The recovery rate was 82.6 % for patients who got a bacteriological examination and 87.6 % for patients who were treated without any bacteriological examination. The difference is not statistically significant. DISCUSSION AND CONCLUSION: These results seem to show that a probabilistic medical care is as effective as (but probably more economical than) a therapeutic strategy guided by the results of further examinations in case of failure of a primary treatment. This conclusion should be confirmed by a medico-economic comparison after randomization.

Activated STING in a vascular and pulmonary syndrome.

BACKGROUND: The study of autoinflammatory diseases has uncovered mechanisms underlying cytokine dysregulation and inflammation. METHODS: We analyzed the DNA of an index patient with early-onset systemic inflammation, cutaneous vasculopathy, and pulmonary inflammation. We sequenced a candidate gene, TMEM173, encoding the stimulator of interferon genes (STING), in this patient and in five unrelated children with similar clinical phenotypes. Four children were evaluated clinically and immunologically. With the STING ligand cyclic guanosine monophosphate-adenosine monophosphate (cGAMP), we stimulated peripheral-blood mononuclear cells and fibroblasts from patients and controls, as well as commercially obtained endothelial cells, and then assayed transcription of IFNB1, the gene encoding interferon-ß, in the stimulated cells. We analyzed IFNB1 reporter levels in HEK293T cells cotransfected with mutant or nonmutant STING constructs. Mutant STING leads to increased phosphorylation of signal transducer and activator of transcription 1 (STAT1), so we tested the effect of Janus kinase (JAK) inhibitors on STAT1 phosphorylation in lymphocytes from the affected children and controls. RESULTS: We identified three mutations in exon 5 of TMEM173 in the six patients. Elevated transcription of IFNB1 and other gene targets of STING in peripheral-blood mononuclear cells from the patients indicated constitutive activation of the pathway that cannot be further up-regulated with stimulation. On stimulation with cGAMP, fibroblasts from the patients showed increased transcription of IFNB1 but not of the genes encoding interleukin-1 (IL1), interleukin-6 (IL6), or tumor necrosis factor (TNF). HEK293T cells transfected with mutant constructs show elevated IFNB1 reporter levels. STING is expressed in endothelial cells, and exposure of these cells to cGAMP resulted in endothelial activation and apoptosis. Constitutive up-regulation of phosphorylated STAT1 in patients' lymphocytes was reduced by JAK inhibitors. CONCLUSIONS: STING-associated vasculopathy with onset in infancy (SAVI) is an autoinflammatory disease caused by gain-of-function mutations in TMEM173. (Funded by the Intramural Research Program of the National Institute of Arthritis and Musculoskeletal and Skin Diseases; ClinicalTrials.gov number, NCT00059748.).

Uric acid and the cardiovascular profile of African and Caucasian men.

The African population is considered a high-risk group for the development of hypertension, and identifying risk factors are therefore essential in preventive actions against cardiovascular disease (CVD). Elevated levels of uric acid (UA) are often associated with CVD. Our first aim was to establish possible ethnic differences in UA levels between African and Caucasian men. Our second aim was to determine any associations between UA levels and cardio-metabolic variables, and also how these correlates differ between the two groups. African (N=87) and Caucasian (N=121) men participated in this cross-sectional study. Our results have shown that African men had significantly lower (353±87.7 vs 401±98.2; P<0.01) UA levels compared with Caucasian men. Waist circumference and triglycerides correlated strongly with UA in both ethnic groups. This was confirmed with a forward stepwise multiple regression analysis. After adjustment for confounders, the correlation between UA and triglycerides remained significant only in the Caucasians (r=0.29; P=0.02), whereas only the African men showed an independent correlation between UA and total peripheral resistance (TPR) (r=0.23; P=0.04). TPR increased significantly across UA tertiles only in the African men (P=0.01 vs P=0.96). In conclusion, despite their lower UA levels, Africans showed an independent relationship between UA and vascular resistance, indicating a possible explanation for their high prevalence of hypertension.

Ethnic and gender differences regarding the insulin-blood pressure relationship.

Ageing is associated with increased insulin and C-peptide levels. Due to a lack of data, our first aim was to establish whether this also holds true for Africans from South Africa. Our second aim was to determine whether an association between insulin/C-peptide levels and blood pressure exist within an African and Caucasian population with increasing age, as well as to establish gender differences. African men and women (N=260) and Caucasian men and women (N=369) were recruited and stratified into age groups (18-35 years, 36-45 years and >45 years). ANCOVAs and partial correlations were performed. Results showed opposing changes in insulin/C-peptide levels of African and Caucasian men with increasing age. Insulin/C-peptide tended to decrease in African men, whereas insulin tended to increase and C-peptide increased significantly (p=0.03) in Caucasian men. Despite similar obesity levels, the oldest African women had significantly lower insulin (p<0.01) and C-peptide (p<0.01) levels compared to their Caucasian counterparts. In conclusion, insulin/C-peptide levels tended to decrease in the African population with increasing age. Despite significantly lower levels of insulin, blood pressure levels of African men seems to be affected more detrimentally compared to their Caucasian counterparts, leaving them more vulnerable for the development of cardiovascular diseases.

Psychological effects of chemical weapons: a follow-up study of First World War veterans.

BACKGROUND: Chemical weapons exercise an enduring and often powerful psychological effect. This had been recognized during the First World War when it was shown that the symptoms of stress mimicked those of mild exposure to gas. Debate about long-term effects followed the suggestion that gassing triggered latent tuberculosis. METHOD: A random sample of 103 First World War servicemen awarded a war pension for the effects of gas, but without evidence of chronic respiratory pathology, were subjected to cluster analysis using 25 common symptoms. The consistency of symptom reporting was also investigated across repeated follow-ups. RESULTS: Cluster analysis identified four groups: one (n=56) with a range of somatic symptoms, a second (n=30) with a focus on the respiratory system, a third (n=12) with a predominance of neuropsychiatric symptoms, and a fourth (n=5) with a narrow band of symptoms related to the throat and breathing difficulties. Veterans from the neuropsychiatric cluster had multiple diagnoses including neurasthenia and disordered action of the heart, and reported many more symptoms than those in the three somatic clusters. CONCLUSIONS: Mild or intermittent respiratory disorders in the post-war period supported beliefs about the damaging effects of gas in the three somatic clusters. By contrast, the neuropsychiatric group did not report new respiratory illnesses. For this cluster, the experience of gassing in a context of extreme danger may have been responsible for the intensity of their symptoms, which showed no sign of diminution over the 12-year follow-up.

A comparison of uric acid levels in Black African vs Caucasian women from South Africa: the POWIRS study.

OBJECTIVES: Elevated levels of uric acid are often associated with cardiometabolic risk factors. The aim of this study was to determine whether uric acid levels differ between African and Caucasian women and whether uric acid is associated with cardiometabolic risk factors within the two ethnic groups. METHODS: Women from African (N=102) and Caucasian (N=115) descent were recruited and their uric acid levels measured. Anthropometric measurements included height (stature), weight, and waist circumference. Correlations between uric acid and cardiometabolic variables within each ethnic group were also determined. RESULTS: African women had significantly lower levels of uric acid (P<.01) and significantly higher levels of blood pressure (P=.05) compared to the Caucasian women. There was a significant increase in blood pressure from the lower to higher uric acid tertiles in the African women. Uric acid strongly correlated with waist circumference in both ethnic groups. CONCLUSIONS: Despite their higher blood pressure, the African women had lower uric acid levels, yet they showed a significant increase in blood pressure from a low uric acid tertile to high uric acid tertile, which was not noticeable in the Caucasian women. A possible explanation is a lower waist circumference in African women compared to Caucasian women.

An audit of study casts used to monitor tooth wear in general practice.

OBJECTIVE: To assess the outcome of compliance of advice sent to patients and dentists about monitoring tooth wear in general practice. METHOD: Postal questionnaires were sent to 70 patients and their dentists requesting information on the outcome of letters of advice sent to general dental practitioners regarding monitoring tooth wear with study casts. They also requested information about the reasons for the patients' referral, the outcome of treatment and whether study models had been taken. RESULTS: Replies were received from 60 dentists (87%) and 53 patients (75%). Of these, 16 patients and 16 dentists had moved from their recorded address. Study casts were reported as having been taken by 23 dentists (38%) and reported by 18 patients (34%). The most common reason for referral was advice about monitoring the wear and the appearance of their teeth. CONCLUSIONS: The compliance of the patients and dentists in monitoring tooth wear by using study casts in general practice was not successful. It raises issues regarding the value of consultant advice letters to this common clinical problem.

Psychological briefing, prevention or priming? or, How many psychiatrists does it take to change a mind?

This paper is a corollary of the recent Class Action against the MoD 2003 and should be read in conjunction with Palmer 2003. As fear is a prerequisite for the diagnosis of Post Traumatic Stress Disorder (PTSD) it was examined in some detail during this case. This paper serves to amplify those deliberations.

The psychological dimension of chemical, biological, radiological and nuclear (CBRN) terrorism.

Terrorism is an increasing feature of the World Scene. In the UK, our perspective has changed from a largely Ireland focused one to a more international view. The United States of America are, for the first time, seen as major terrorist targets. We are now "at war with terrorism". The medical aspects of terrorism have been extensively discussed in this journal and elsewhere, this article specifically addresses the psychological consequences of the use of terror weapons.

Chemical, biological, radiological and nuclear terrorism: an introduction for occupational physicians.

BACKGROUND: Chemical, biological, radiological and nuclear terrorism poses considerable threat throughout the world. AIM: To provide occupational physicians with an understanding of this threat and its main forms and what action can be taken to counter this threat. METHODS: Presenters at a conference on chemical, biological, radiological and nuclear terrorism were asked to contribute their evidence-based opinions in order to produce a review article. RESULTS: This paper presents a summary of the different forms of chemical, biological, radiological and nuclear terrorism and the effective counter-measures and also provides a review of current scientific literature. CONCLUSION: The threat of chemical, biological, radiological and nuclear terrorism is present throughout the world and is one that occupational physicians should be aware of, as well as the action that can be taken to counter it.

Sexuality and soldiery combat & condoms, continence & cornflakes.

The results of a short sexual health study of 75 male soldiers undertaking humanitarian aid relief in Africa are presented in an historical context relating to sexuality and soldiery.

The health effects of peace-keeping in the UK Armed Forces: Bosnia 1992-1996. Predictors of psychological symptoms.

BACKGROUND: Peace-keeping duties are associated with unique stresses for military personnel. There have been few reports on the effects of peace-keeping on psychological health. METHOD: We used data from a cross-sectional study originally established to examine health effects of service in the Gulf War, which included a control group who had been deployed in Bosnia (N= 2049). This group was examined to establish which demographic, occupational, and deployment-related risk factors were associated with psychological distress measured on the General Health Questionnaire (GHQ-12) and stress symptoms akin to a post-traumatic stress reactions. RESULTS: The main risk factors for stress symptoms in the Bosnia group were--lower rank, being deployed early in the campaign, having more deployment-related exposures, and serving on staff duties. There was no protective effect of previous deployments to the Falklands or Northern Ireland, and time off following deployment was not protective. For GHQ-12 cases, the main risk factors were: female gender, lower rank, increased deployment-related exposures and serving on staff duties. CONCLUSIONS: This study suggests that stress symptoms and GHQ-12 cases, are strongly predicted both by experiences during deployment and demographic factors.

Folding and purification of insoluble (inclusion body) proteins from Escherichia coli.

Heterologous expression of recombinant proteins in E. coli often results in the formation of insoluble and inactive protein aggregates, commonly referred to as inclusion bodies. To obtain the native (i.e., correctly folded) and hence active form of the protein from such aggregates, four steps are usually followed: (1) the cells are lysed and the are aggregates, (2) the cell wall and outer membrane components of the aggregates are removed, (3) the aggregates are solubilized (or extracted) with strong protein denaturants, and (4) the solubilized, denatured proteins are folded with concomitant oxidation of reduced cysteine residues into the correct disulfide bonds to obtain the native protein. This unit features three different approaches to the final step of protein folding and purification. In the first, guanidine HCl is used as the denaturant, after which the solubilized protein is folded (before purification) in an "oxido-shuffling" buffer system to increase the rate of protein oxidation. In the second, acetic acid is used to solubilize the protein which is then partially purified by gel filtration before folding, and then the protein is folded and oxidized by simple dialyzed against water. A Support Protocol is included for rapidly determining the amount of folded protein that contains the correct disulfide linkage pattern. Finally, folding and purification of a fusion protein is described using metal-chelate affinity chromatography.