Investigation and control of an outbreak due to a contaminated hospital water system, identified following a rare case of Cupriavidus pauculus bacteraemia.

BACKGROUND: Cupriavidus pauculus is rare cause of clinical infection. We describe an outbreak of C. pauculus and other Gram-negative bacteraemias in a paediatric haemato-oncology unit secondary to a contaminated water supply and drainage system. AIM: To describe the investigation and control measures implemented for a waterborne infection outbreak in a new build hospital. METHODS: Extensive water testing from various points within the water system was undertaken. Taps, showerheads and components including flow straighteners underwent microbiological analysis. Drains were also swabbed. Surveillance for Gram-negative infections was established on the unit. FINDINGS: Water testing revealed widespread contamination of the water and drainage system. Outlets were also heavily contaminated, including flow straighteners. Drains were found to have underlying structural abnormalities. Water testing enabled us to detect high-risk components within the water system such as the expansion vessels and outlets and the results assisted with hypotheses generation. Review of commissioning data and risk assessments revealed extensive risks present within the water system prior to and after hospital opening. CONCLUSION: Careful design, adequate control measures and maintenance are essential for hospital water systems in order to prevent infections due to waterborne organisms. We discuss what can be learned from this incident with a view to future prevention.

The management of menopausal symptoms in women following treatment for cancer at a specialist menopause service.

OBJECTIVE: The aim of this study was to identify prescribing patterns at a specialist menopause service in a central London teaching hospital for women following treatment for a malignancy. STUDY DESIGN: This was a prospective cohort study with data collected over a seven-month period from December 2019 to June 2020. All women reviewed at the specialist menopause services following treatment of a malignancy, BRCA carriers and Lynch syndrome were included in the study, with management options divided into three categories: hormonal, non-hormonal and no treatment. MAIN OUTCOME MEASURES: The primary outcome of this study was to identify prescribing patterns for all women reviewed following a diagnosis of a malignancy, as well as those with genetic mutations necessitating risk-reducing prophylactic bilateral salpingo-oopherectomy (BSO). RESULTS: Altogether 71 women were included in this study, with the majority of women post management of a non-gynaecological malignancy (51/71, 72%), of which breast cancer was the most common (37/71, 52%). While non-hormonal treatment was the most popular among those treated for breast cancer, for all other malignancies, hormonal treatment was more widespread. Fourteen women also had genetic mutations, with all of these women commencing hormonal treatment post risk reducing surgery. CONCLUSION: With the exception of those with a history of hormone-sensitive breast cancer, the use of hormonal treatment for menopausal symptoms remained widespread. While this was a relatively small study, the need for long-term follow-up across specialist menopause services, to assess the risk of recurrence is vital.

The testosterone prescribing practice of BMS menopause specialists.

The NICE Guidelines published in 2015 state that testosterone supplementation can be considered for menopausal women with low sexual desire if hormone replacement therapy alone is not effective. There is however, no detail on what to prescribe, how much to prescribe or whether monitoring is required. At the time of conception of this project, there was no national guideline or official advice from the British Menopause Society. We decided to ask menopause experts from around the UK to see if a consensus could be reached about good prescribing practice. The method and results as discussed below may be helpful in future recommendations and guidance.

Evaluation of a tertiary and district general hospital menopause service.

OBJECTIVE: Requests for management of menopausal symptoms and hormone replacement are increasing in the UK. Referrals to specialist clinics have to be balanced with increasing recommendations within the NHS to improve efficiency and patient care. STUDY DESIGN: Retrospective evaluation of clinic records over two months at a district general (Poole Hospital) and tertiary (Guy's Hospital) menopause service. Data on referral origin, reason for referral, interval from referral to review and outcome were collected and compared between trusts. MAIN OUTCOME MEASURES: To evaluate and compare referrals and outcomes in a tertiary and district general menopause service and provide recommendations for improving efficiency. RESULTS: Most referrals are from primary care but up to 25% are from other specialties. Half of the appointments are new referrals and 95% of women attend. Of the new referrals, 50% have multiple medical comorbidities, 25% a personal or family history of cancer and 25% treatment resistance; 30% have premature ovarian insufficiency. At Guy's Hospital, 30% are reviewed more than 18 weeks after referral, at Poole Hospital this is 6%. Treatment resistance is reported in half of the women reviewed at follow-up. CONCLUSIONS: Menopause services review a complex patient population and the majority of referred women have more than one co-morbidity; they require time, specialist knowledge of current treatment options and a multidisciplinary approach. The main barrier to service efficiency is capacity, particularly in population dense areas; cognitive behavioural therapy and non-hormonal methods appear under-utilised in primary care, as do alternative methods of follow-up within the clinics such as telephone and patient-initiated appointments.

Collaborating to Compete: Blood Profiling Atlas in Cancer (BloodPAC) Consortium.

The cancer community understands the value of blood profiling measurements in assessing and monitoring cancer. We describe an effort among academic, government, biotechnology, diagnostic, and pharmaceutical companies called the Blood Profiling Atlas in Cancer (BloodPAC) Project. BloodPAC will aggregate, make freely available, and harmonize for further analyses, raw datasets, relevant associated clinical data (e.g., clinical diagnosis, treatment history, and outcomes), and sample preparation and handling protocols to accelerate the development of blood profiling assays.

Evolutionary Design of Gene Networks: Forced Evolution by Genomic Parasites.

The co-evolution of species with their genomic parasites (transposons) is thought to be one of the primary ways of rewiring gene regulatory networks (GRNs). We develop a framework for conducting evolutionary computations (EC) using the transposon mechanism. We find that the selective pressure of transposons can speed evolutionary searches for solutions and lead to outgrowth of GRNs (through co-option of new genes to acquire insensitivity to the attacking transposons). We test the approach by finding GRNs which can solve a fundamental problem in developmental biology: how GRNs in early embryo development can robustly read maternal signaling gradients, despite continued attacks on the genome by transposons. We observed co-evolutionary oscillations in the abundance of particular GRNs and their transposons, reminiscent of predator-prey or host-parasite dynamics.

A service evaluation of women attending the menopause/premature ovarian failure clinic of a tertiary referral centre.

This service evaluation aimed to characterise the referrals to the premature ovarian failure clinic, including the type of referral and patient needs, in order to plan for future service provision. The majority of women seen in the clinic experienced idiopathic premature ovarian failure, were aged 30-39 and were nulliparous at the time of diagnosis. Our service requires to be tailored to their needs. For many women, this includes a fertility consultation in the clinic and this part of the service is well used. Our data support the long-term follow-up of women both on treatment and those who initially decline treatment. Most women who initially decline treatment accept it after a few clinic visits. This may be due to consistent advice on the benefits of oestrogen treatment or due to yearly bone scans showing a change in bone density. There was a high non-attendance rate in this group: 21% of appointments were not attended.

An overview of the menopause: assessment and management.

This article provides an overview of the menopause, including symptom management with medical and non-medical treatments. The article also examines the particular needs of women undergoing early menopause. It discusses the nurse's role in promoting health and providing appropriate and evidence-based advice to enable women to make informed decisions.

Skeletal muscle metastasis from uterine leiomyosarcoma.

A case of a 68-year-old woman who presented with a rapidly enlarging painful right thigh mass is presented. She had a known diagnosis of uterine leiomyosarcoma following a hysterectomy for dysfunctional uterine bleeding. She subsequently developed a single hepatic metastatic deposit that responded well to radiofrequency ablation. Whole-body MRI and MRA revealed a vascular mass in the sartorius muscle and a smaller adjacent mass in the gracilis muscle, proven to represent metastatic leiomyosarcoma of uterine origin. To our knowledge, metastatic uterine leiomyosarcoma to the skeletal muscle has not been described previously in the English medical literature.

Dose-time relationships for elicitation of contact allergy to para-phenylenediamine.

Skin-sensitizing chemicals exhibit dose-response relationships for the elicitation of contact dermatitis. Previously, considerable work has been carried out in which the elicitation of allergic skin reaction has been examined as a function of the applied concentration. However, the relationship between exposure time, dose and response has not been explored in any depth. The present work has extended our initial assessment of the relationship between both exposure time and concentration for para-phenylenediamine (PPD) in a group of 19 PPD-allergic volunteers. The results clearly demonstrate that a relationship exists between both exposure time and concentration. Positive responses to PPD were directly proportional to exposure time: at 5 min 16% responded; at 15 min, 38%; at 30 min, 50%; and at 120 min, 69%. A similar direct relationship was found between concentration of PPD and response: after 120 min, 22% of patients had responded to 0.01%, and 69% to 1% PPD. All exposures for 1 and 2 min were negative. Subsequent evaluation using repeated 5 min open application testing demonstrated a cumulative effect, as after 8 days 39% of the panel reacted, more than double the number that reacted to a single occluded 5-min treatment. It was noted that there was marked subject variability in exposure time and dose required to elicit an allergic response. These results are of relevance for the general interpretation of patch test data, especially with regard to risk assessment.

Skin irritation thresholds in hairdressers: implications for the development of hand dermatitis.

BACKGROUND: Individuals vary in their ability to react to irritants. OBJECTIVES: To observe the development of clinical hand dermatitis and sensitization prospectively in trainee hairdressers and to compare this with their irritant threshold to sodium lauryl sulphate (SLS). METHODS: Subjects were patch tested to a limited series of occupational importance and their irritant threshold to SLS was determined; patch testing was repeated 6 months later and subjects were assessed for hand dermatitis. RESULTS: The development of hand dermatitis was associated with a lower irritant threshold. A similar association was not found for sensitization. CONCLUSIONS: The development of clinical dermatitis in prospectively followed subjects with greater irritant reactivity has not previously been identified. The association of greater irritant reactivity with a proinflammatory cytokine polymorphism may partly explain this. Further development of the irritant threshold test could contribute to the identification of non-atopic subjects at risk of occupational skin disease.

Time-resolved phosphorescence of tyrosine, tyrosine analogs, and tyrosyl residues in oxytocin and small peptides.

We present the time-resolved phosphorescence of oxytocin, two oxytocin derivatives, vasopressin and a series of compounds that serve as models for free tyrosine. One of the oxytocin derivatives, desaminodicarbaoxytocin, has the disulfide bridge replaced by an ethylene bridge, and lacks the N-terminus. Similar to the reported fluorescence decays of tyrosine in these peptides, the phosphorescence decays generally are not single exponentials, but can be fit as biexponentials. The decay times for the oxytocin peptides are shorter than for desaminodicarbaoxytocin or the model compounds, and this we attribute to enhanced spin-orbit coupling due to the presence of sulfur. We measured the phosphorescence decay of the model cyclic pentapeptide that contains tyrosine and compared it to that observed for the same cyclic pentapeptide in which tyrosine is replaced by tryptophan. We also report the phosphorescence of 2-tryptophan-oxytocin, and deamino-2-tryptophan-oxytocin in which biexponential phosphorescence decay is also observed.

High-level expression of three members of the murine angiogenin family in Escherichia coli and purification of the recombinant proteins.

Angiogenin (Ang) is a small basic protein which belongs to the pancreatic ribonuclease superfamily. It potently induces the formation of new blood vessels and has emerged as a promising anticancer target. Mice possess genes encoding one ortholog (mAng) and three homologs of Ang, designated angiogenin-related protein (mAngrp), angiogenin-3 (mAng-3), and angiogenin-4 (mAng-4). Structural and functional study of these homologs has been hampered by the low yield of protein from the existing heterologous expression system. In the experiments described, we used a pET expression vector to express these proteins in the cytoplasm of Escherichia coli BL21-CodonPlus(DE3)-RIL cells, whereupon substantial amounts of each accumulated in the form of insoluble aggregates. The proteins were renatured using an arginine-assisted procedure and subsequently purified by cation-exchange chromatography and reversed-phase HPLC; each purified protein was shown to be enzymatically active toward tRNA. The yields of pure mAngrp and mAng-3 were 7.6 and 12 mg/liter culture, respectively, representing substantial increases over previously reported experiments. This is also the first report of the expression and purification of mAng-4, obtained here in a yield of 30 mg/liter culture. The ready availability of milligram quantities of these proteins will enable further functional studies and high-resolution structural analyses to be conducted.

Managing a complex river catchment: a case study on the River Almond.

The River Almond catchment in the east central belt rates amongst Scotland's most polluted rivers. This paper describes how shifting forms of economic development in the catchment since the 1860s have affected river quality. A legacy of effects from past land uses has combined with the impacts associated with current land uses to present a substantial and complex management challenge. It is argued that there have been, and still are, scientific, legislative and socio-economic constraints on the abilities of managers to respond promptly to changing patterns of impacts on the river system. This response lag has tended to increase the costs of subsequent remediation, and has consequently supported a downward pressure on the quality standards that are considered 'realistic' by river managers. Conversely, advances in science, the expansion of regulatory powers and resources, and an increase in public interest in the environment has helped to clarify the extent of the management problems in the catchment, and allowed major advances in some areas of pollution management. In an attempt to overcome some of the remaining weaknesses of river management, river managers and interest groups have started to form inter-sectoral and multidisciplinary partnerships. The success of these new groupings is highly contingent, not so much on the competence of their scientific advice, but on the priority given to water protection by the land-use decision-makers involved, and the resources they are prepared to commit to funding rehabilitation.

The effect of a single dose of osteoprotegerin in postmenopausal women.

Osteoprotegerin (OPG), a tumor necrosis factor (TNF) receptor family member, is a critical regulator of bone resorption. It is an important inhibitor of the terminal differentiation and activation of osteoclasts. This randomized, double-blind, placebo-controlled, sequential dose escalation study was conducted in postmenopausal women to determine the effect of a single subcutaneous (s.c.) dose of OPG on bone resorption as indicated by the biochemical markers, urinary N-telopeptide (NTX) and deoxypyridinoline (DPD), which are stable collagen degradation products. NTX levels decreased within 12 h after OPG administration. At the highest dose administered (3.0 mg/kg), a mean percent decrease in NTX of approximately 80% was observed 4 days after dosing. Six weeks after dosing a mean decrease of 14% in NTX was observed. The levels of bone-specific alkaline phosphatase (BSAP), a marker of bone formation, did not change for approximately 3 weeks after dosing. Thereafter, a modest decrease, reaching approximately 30% at 6 weeks, was observed in the 3.0-mg/kg dose group. The rapid decrease from baseline in NTX and delayed decrease in BSAP indicated that OPG acted primarily on osteoclasts to decrease bone resorption. OPG injections are well tolerated. This study, for the first time, indicates that a single s.c. injection of OPG is effective in rapidly and profoundly reducing bone turnover for a sustained period and that OPG therefore may be effective in treatment of bone diseases characterized by increased bone resorption such as osteoporosis.

An education programme for professionals who specialize in substance misuse in St Petersburg, Russia: part 1.

This paper provides an account of a joint project of education and training of doctors and nurses in St Petersburg, funded by the Know How Fund Health Sector Small Partnership Scheme (Russia). Contextual material on drug and alcohol misuse in Russia is introduced prior to a focus on the drug and alcohol misuse issues in St Petersburg. Reference is made to historical and contemporary material on alcohol and drug misuse, and attention is drawn to the reliability of statistical data. The main aims of the project and the work carried out are outlined. Firstly, to bring together medical and nursing colleagues, enabling a recognition of the overlap in training and educational needs of both professional groups, and the learning that can occur from understanding each others roles and responsibilities. Secondly, that the theory and practice of different approaches to care and treatment can be incorporated into already established curricula used to educate both nurses and doctors. Colleagues in St Petersburg have requested the support and guidance of UK practitioners and nurse educationalists to facilitate these changes in perspectives. The paper concludes with a brief discussion of the influence of the project in anticipation of a forthcoming paper that will detail evaluation processes that the provision has undergone and examine the findings in more detail.

Complex morphogenesis of surfaces: theory and experiment on coupling of reaction-diffusion patterning to growth.

Reaction-diffusion theory for pattern formation is considered in relation to processes of biological development in which there is continuous growth and shape change as each new pattern forms. This is particularly common in the plant kingdom, for both unicellular and multicellular organisms. In addition to the feedbacks in the chemical dynamics, there is then another loop linking size and shape changes with the reaction-diffusion patterning of growth controllers in the growing region. In studies by computation, the codes must incorporate, alongside the usual solvers of the partial differential dynamic equations, a versatile growth code, to express any kind of shape change. We have found that regulation of shape change in particular ways (e.g. to make narrow-angle branchings) demands new features in our chemical mechanisms. Our growth algorithm is for a surface growing tangentially, but moving outward and changing shape to accommodate the extra area. This is potentially applicable both to the tunica layer of multicellular plant meristems and to the growing tip of the cell surface, e.g. in the morphogenesis of single-celled chlorophyte algae which display branching processes: whorl formation in Acetabularia (Dasycladales) and repeated dichotomous branching in Micrasterias (Desmidiaceae). For computational studies, a hemispherical shell is a reasonable idealization of the initial shape. We describe results of two types of study: (1) Pattern formation by three reaction-diffusion models, with contrasted nonlinearities, on the hemispherical shell, particularly to find conditions for robust formation of annular pattern or pattern for dichotomous branching, both of which are common in plants. (2) Sequential dichotomous branchings in a system growing and changing in shape from the hemispherical start.

Technical advance: application of high-performance liquid chromatography with photodiode array detection to the metabolic profiling of plant isoprenoids.

The application of high-performance liquid chromatography (HPLC) using a C30 reverse-phase stationary matrix has enabled the simultaneous separation of carotenes, xanthophylls, ubiquinones, tocopherols and plastoquinones in a single chromatogram. Continuous photodiode array (PDA) detection ensured identification and quantification of compounds upon elution. Applications of the method to the characterization of transgenic and mutant tomato varieties with altered isoprenoid content, biochemical screening of Arabidopsis thaliana, and elucidation of the modes of action of bleaching herbicides are described to illustrate the versatility of the procedure.

Benzalkonium chloride neutralizes the irritant effect of sodium dodecyl sulfate.

When benzalkonium chloride (BKC), a cationic surfactant, is added to sodium dodecyl sulfate (SDS), an anionic surfactant, and used in patch testing, on the basis of their known physicochemical interaction, it is possible to predict that there will be a tendency towards a reduction in the expected irritant response when compared to SDS alone. The aim of this study was to investigate whether BKC could reduce the irritant response to SDS when applied after the SDS exposure. 54 non-atopic adult volunteers were recruited for the study. 20% SDS was applied for 2 h under occlusion. 1% BKC was then applied to the same site. Various controls, including SDS application followed by water for 2 h, were included. The irritant reaction was assessed at 24 h and 48 h. 40 of the 54 subjects had some reaction when SDS was applied for 2 h followed by either benzalkonium chloride or water control under occlusion. In comparison to water control, where BKC was applied after SDS, 20 of the 40 responders had a weaker reaction but only 4 had a stronger response. This study shows that BKC applied to skin exposed to SDS attenuates the resulting irritant reaction.

The frequency of fragrance allergy in a patch-test population over a 17-year period.

Fragrances are widely encountered in our daily environment and are known to be a common cause of allergic contact dermatitis. We have reviewed our patch test data from 1980 to 1996 to establish whether the pattern of fragrance allergy has changed with time. During this period, 25,545 patients (10,450 male, 15,005 female) were patch tested with the European standard series. The mean annual frequency of positive reactions to the fragrance mix was 8.5% in females (range 6.1-10.9) and 6.7% in males (range 5.1-12.9). Females were 1.3 times more likely to be allergic to fragrance (P < 0.001, 95% confidence interval, CI 1.17-1.41). Males with fragrance allergy were older than females by 5.6 years (mean age 48.2 vs. 42.6 years; P < 0.001, 95% CI 3.9-7.3). The incidence of a concomitant positive patch test to balsam of Peru in fragrance-sensitive patients showed wide variation, suggesting that it is not a reliable marker of fragrance allergy. There was a positive correlation between the isomers isoeugenol and eugenol. Oak moss remained the most common overall allergen throughout the study, positive in 38.3% of females and 35.6% of males who were tested to the constituents of the fragrance mix. During the period of the study the incidence of positive tests to oak moss increased by 5% yearly (P = 0.001, 95% CI 2.2-8.7). The frequency of allergic reactions to eugenol and geraniol remained relatively constant. Isoeugenol and alpha-amyl cinnamic aldehyde sensitivity increased and hydroxycitronellal showed a slow decline. There was a striking reduction in the frequency of sensitivity to cinnamic aldehyde (by 18% yearly; P < 0.001, 95% CI 14.3-21.0) and cinnamic alcohol (by 9% yearly; P < 0.001, 95% CI 5.2-12.9); these are now uncommon fragrance allergens. These data show temporal trends which may reflect the frequency of population exposure to individual fragrances.