Meningoencephalitis in a Royal Marine after skinning reindeer in Norway.

Meningoencephalitis presenting in service personnel overseas may present a diagnostic challenge due to the broad range of potential differential diagnosis as well as the requirement for rapid assessment and treatment. A 25-year-old Royal Marine was evacuated to the Royal Centre for Defence Medicine in Birmingham, UK, with a history of rash consistent with erythema chronicum migrans, a seizure, and lymphocytic pleocytosis after skinning reindeer in Norway. Neuroborreliosis was suspected and empirical antibiotics were administered. Despite subsequent negative serology for Borrelia burgdorferi, given the clinical features and lymphocytic pleocytosis, an atypical presentation of neuroborreliosis remains a possible diagnosis in this scenario. This case serves to illustrate that British military personnel on exercise are potentially at risk of contracting borreliosis both in the UK and abroad, serological tests can be unreliable, and the differential diagnosis of meningoencephalitis can be broad with specialist input often required.

Snakebites in Africa and Europe: a military perspective and update for contemporary operations.

Snakebite envenoming is rare among military patients, with few cases reported in recent years. Increasingly, however, military operations are taking place in remote parts of Africa, which are inhabited by numerous species of venomous snake, and in Europe, where dangerous species exist but are less common. Bites from a venomous snake may prove fatal, and therefore military medics must be adequately prepared to manage them. This paper reviews the most medically significant species of venomous snake present in Africa and Europe, before suggesting an evidence-based approach to snakebite prevention and management, including possible changes to the UK's Clinical Guidelines for Operations.

Towards research combat readiness: prepared, prospective and preapproved.

Research drives the advancement of medical knowledge during war, but planning and execution are too slow to enable early data acquisition. Future conflicts are likely to be shorter and more dispersed, requiring innovation to avoid missing out on the crucial early stages. To seize the initiative, we suggest that a collection of preapproved research studies be designed, stored and maintained within the medical command structure so that they are ready for immediate implementation at the onset of future conflicts, even during the most kinetic early phases of deployment.

A 2-year review of the general internal medicine admissions to the British Role 3 Hospital in Camp Bastion, Afghanistan.

BACKGROUND: Detailed knowledge of the likely volume and nature of the diseases presenting to deployed secondary care facilities aids operational planning. Now the British operation in Afghanistan has ended and a record of the experience is useful to preserve the lessons learned. METHODS: Over a 2-year period from April 2011, prospective demographic and clinical data were collected on consecutive general internal medicine admissions to the Role 3 Hospital in Camp Bastion, Afghanistan. Up to four different symptoms and diagnoses were coded using the WHO International Classification of Disease, V.10 for each patient. RESULTS: A total of 1368 medical patients were admitted. Of 1131 military admissions, 612 were from the UK (54.1%) and the remainder from 13 allied countries; 237 civilians came from 23 countries. Civilians were older than the military patients (p<0.001) but included five children. The 20 most frequent presenting symptoms were identified and there were 1626 diagnoses made. The 10 most frequent diagnoses were infectious gastroenteritis (12.6%), heat illness (4.3%), pneumonia (3.6%), epilepsy (2.6%), cellulitis (2.7%), migraine (1.8%), peptic ulcer disease (1.2%), myocardial infarction (1.2%), venous thromboembolism (1.2%) and pericarditis (0.7%). In 252 cases (18.4%) a firm diagnosis was not reached and a symptom was recorded. The five most frequent of these were undifferentiated febrile illnesses (4.6%), syncope (3.7%), chest pain (2.8%), headache (0.8%) and palpitations (0.7%). The mean hospital length of stay was 1.59 days and 72.2% of UK military patients were 'returned to unit'. Three civilian patients died in hospital or following aeromedical evacuation and there were no deaths of any military patients. DISCUSSION: This study demonstrates the wide variety of presentations seen by physicians at an established military field hospital. This information informs the core syllabus of military physician training and will help facilitate planning for future medical support to similar military operations. TRIAL REGISTRATION NUMBER: RCDM/Res/Audit/1036/12/0305.

Medical civil-military interactions on United Nations missions: lessons from South Sudan.

This paper outlines the United Nations' integrated response to complex humanitarian emergencies and the different types of interactions that may occur between militaries and civilian organisations involved in them. It uses a recent UK deployment to South Sudan as an example, drawing on the experience to highlight areas of particular interest to healthcare workers. It identifies several domains that should usefully be developed for both civilians and military personnel in these environments-including sharing our expertise in major incident management, proof-of-concept testing for novel diagnostic and treatment solutions and offering to engage in joint continuing medical education. These gaps in organisational policy should be addressed and appropriate training pathways designed to maximise the contribution of the Defence Medical Services in similar contexts in the future.

Undifferentiated febrile illnesses in South Sudan: a case series from Operation TRENTON from June to August 2017.

Undifferentiated febrile illnesses present diagnostic and treatment challenges in the Firm Base, let alone in the deployed austere environment. We report a series of 14 cases from Operation TRENTON in South Sudan in 2017 that coincided with the rainy season, increased insect numbers and a Relief in Place. The majority of patients had headaches, myalgia, arthralgia and back pain, as well as leucopenia and thrombocytopenia. No diagnoses could be made in theatre, despite a sophisticated deployed laboratory being available, and further testing in the UK, including next-generation sequencing, was unable to establish an aetiology. Such illnesses are very likely to present in tropical environments, where increasing numbers of military personnel are being deployed, and clinicians must be aware of the non-specific presentation and treatment, as well as the availability of Military Infection Reachback services to assist in the management of these cases.

Enhanced case management can be delivered for patients with EVD in Africa: Experience from a UK military Ebola treatment centre in Sierra Leone.

BACKGROUND: Limited data exist describing supportive care management, laboratory abnormalities and outcomes in patients with Ebola virus disease (EVD) in West Africa. We report data which constitute the first description of the provision of enhanced EVD case management protocols in a West African setting. METHODS: Demographic, clinical and laboratory data were collected by retrospective review of clinical and laboratory records of patients with confirmed EVD admitted between 5 November 2014 and 30 June 2015. RESULTS: A total of 44 EVD patients were admitted (median age 37 years (range 17-63), 32/44 healthcare workers), and excluding those evacuated, the case fatality rate was 49% (95% CI 33%-65%). No pregnant women were admitted. At admission 9/44 had stage 1 disease (fever and constitutional symptoms only), 12/44 had stage 2 disease (presence of diarrhoea and/or vomiting) and 23/44 had stage 3 disease (presence of diarrhoea and/or vomiting with organ failure), with case fatality rates of 11% (95% CI 1%-58%), 27% (95% CI 6%-61%), and 70% (95% CI 47%-87%) respectively (p = 0.009). Haemorrhage occurred in 17/41 (41%) patients. The majority (21/40) of patients had hypokalaemia with hyperkalaemia occurring in 12/40 patients. Acute kidney injury (AKI) occurred in 20/40 patients, with 14/20 (70%, 95% CI 46%-88%) dying, compared to 5/20 (25%, 95% CI 9%-49%) dying who did not have AKI (p = 0.01). Ebola virus (EBOV) PCR cycle threshold value at baseline was mean 20.3 (SD 4.3) in fatal cases and 24.8 (SD 5.5) in survivors (p = 0.007). Mean national early warning score (NEWS) at admission was 5.5 (SD 4.4) in fatal cases and 3.0 (SD 1.9) in survivors (p = 0.02). Central venous catheters were placed in 37/41 patients and intravenous fluid administered to 40/41 patients (median duration of 5 days). Faecal management systems were inserted in 21/41 patients, urinary catheters placed in 27/41 and blood component therapy administered to 20/41 patients. CONCLUSIONS: EVD is commonly associated life-threatening electrolyte imbalance and organ dysfunction. We believe that the enhanced levels of protocolized care, scale and range of medical interventions we report, offer a blueprint for the future management of EVD in resource-limited settings.

Use of an ultraviolet tracer in simulation training for the clinical management of Ebola virus disease.

In October 2014 the UK military deployed to Sierra Leone to provide care for healthcare workers affected by Ebola virus disease. A training package designed by the Army Medical Services Training Centre prepared the deploying personnel in the required infection prevention and control measures. The training used ultraviolet tracer to provide validation of the skills required when treating patients with Ebola and to confirm subsequent decontamination. This training construct provided useful feedback to clinicians on their infection control measures and would be useful in the context of any infection spread by droplets and fomites.

Evidence for autocrine or paracrine roles of alpha2-macroglobulin in regulation of estradiol production by granulosa cells and development of dominant follicles.

alpha(2)-Macroglobulin (alpha(2)-M) inhibits proteinases and modulates the actions of growth factors and cytokines. Despite the key roles proteinases, growth factors, and cytokines have in folliculogenesis, the role of alpha(2)-M in follicular development is unknown. Our objectives were to: 1) determine whether granulosa cells produce alpha(2)-M and have alpha(2)-M receptors, 2) examine the effect of alpha(2)-M on estradiol production by granulosa cells, 3) establish whether amounts of alpha(2)-M and alpha(2)-M receptors were altered during dominant nonovulatory follicle development, and 4) examine alpha(2)-M's mechanism of action. The results demonstrated that bovine granulosa cells contain 5.2- and 15-kb mRNAs and 720- and 500-kDa proteins that correspond, respectively, to sizes of mRNAs and proteins for alpha(2)-M and the alpha(2)-M receptor. Treatment of granulosa cells with alpha(2)-M resulted in a specific dose-responsive increase in estradiol production. Cell viability, cell number, and the amount of aromatase in granulosa cells were not altered by alpha(2)-M. Treatment of granulosa cells with factors that bind alpha(2)-M or its receptor did not mimic alpha(2)-M action. Although intrafollicular amounts of alpha(2)-M remained unchanged, amounts of alpha(2)-M receptor in granulosa cells were strongly inversely associated with concentrations of estradiol in dominant and subordinate follicles. Based on these results, we concluded that alpha(2)-M may have autocrine or paracrine roles in granulosa cells potentially important for regulation of estradiol production and development of dominant follicles.

Optimization of the human factor VIII complementary DNA expression plasmid for gene therapy of hemophilia A.

While the gene delivery vehicle is critical for the efficacy of human factor VIII gene therapy, optimization of the potency and duration of the factor VIII gene that is delivered is equally important in light of the poor transcription and translation characteristics of this gene. We discuss here a systematic approach to optimization of factor VIII complementary DNA expression by analysis of specific elements engineered into the transcription unit and other positions in the expression plasmid. Within the transcription unit we have engineered different 5' and 3' sequence modifications and tested them for factor VIII expression in human liver cells. These changes incorporate liver-specific promoter and enhancer sequences and regulatory elements affecting RNA export. Specifically, the thyroid hormone-binding globulin promoter and alpha 1 microglobulin/bikunin enhancer were tested and a synthetic 5' intron was compared to a 3' post-transcriptional regulatory element on factor VIII expression levels. For translation optimization, a leader sequence was designed to be of optimum length, have no RNA secondary structure and contain the optimal translation initiation sequence. Finally, we discuss areas for plasmid optimization, which include removal of near-consensus splicing sequences, the inclusion of strong transcription termination elements and the use of autonomous replicating plasmid sequences for episomal maintenance and enhanced plasmid retention for duration of gene expression.

Cisplatin vestibular ototoxicity: preliminary report.

Sixteen patients were monitored for vestibular ototoxicity while receiving cisplatin in dosages of 180 mg/M2. The incidence of preexisting vestibular functional abnormalities (31%) was higher than the incidence of ototoxicity (18%). Although the number of patients was not large enough for meaningful statistical comparison, the incidence of vestibular ototoxicity from cisplatin was low for the dosage levels employed. Based upon the results of this study, the following recommendations are made for monitoring cisplatin vestibular ototoxicity. 1. All patients should receive vestibular tests prior to cisplatin administration. 2. Subjects, who have reduced (or asymmetric) vestibular function upon pretherapy testing, should be monitored at least weekly for any change in function while receiving cisplatin. 3. Subjects who are normal prior to therapy need to be tested only when cumulative doses exceed 400 mg. The severe nausea and vomiting associated with cisplatin chemotherapy is not related to vestibular ototoxicity.

Diagnosis and management of drop attacks of vestibular origin: Tumarkin's otolithic crisis.

Erroneous signals of vestibular origin can cause sudden falls without warning. Drop attacks of vestibular origin in our experience most commonly occurred in patients with late or end-stage endolymphatic hydrops (usually idiopathic, ie, Meniere's disease). Eponymically termed Tumarkin's otolithic crisis, drop attacks of vestibular origin must be distinguished from drop attacks due to cardiovascular abnormalities, seizure disorders, vertebral basilar arterial insufficiency (transitory brain stem ischemia), multiple sclerosis, and drug-induced motor control disturbances. The treatment of choice for drop attacks of vestibular origin is either surgical ablation (labyrinthectomy) in the absence of serviceable hearing or middle fossa vestibular nerve section in order to preserve serviceable hearing.

Vestibular ototoxicity of prophylactic aminoglycoside antibiotics in head and neck cancer patients.

The effect of prophylactic aminoglycoside antibiotics upon vestibular function was studied using a double-blind protocol in a group of head and neck cancer patients scheduled for contaminated (skin-to-mucosa) surgical procedures. The amplitude (gain) of vestibular responses to rotation temporarily declined in 12 of 25 patients postoperatively. There was no correlation between temporary decline in vestibular response and administration of gentamicin, clindamycin, and cefazolin. After a recovery period of one to three months, none of the patients showed evidence of vestibular aminoglycoside ototoxicity. The transient reduction in vestibular responses to rotary stimuli was possibly related to the use of analgesics, anesthetic agents, or radical neck dissection procedures. The importance of repeat measures and proper timing of vestibular ototoxic monitoring procedures in a surgical patient population was demonstrated by this study. Results of this study may also impact interpretation of findings from certain surgical procedures performed for control of vertigo.

The occurrence of reinforcing activities in relation to locus of control, success-failure expectancies, and physical attractiveness.

The Pleasant Events Schedule (mimeographed), which measures the retrospective frequency and value of positive reinforcement, was administered to 74 college students; and its relation to subjects' locus of control and success-failure expectancies and to their levels of physical attractiveness was evaluated. While results were less consistent for females than for males, significant relationships were obtained between each of these "person" variables and the various indices derived from the Pleasant Events Schedule. Not only do the findings reflect favorably on the construct validity of the various dimensions as measured, but the data carry implications for a more integrative study of depression.

A method for measuring "primitive" and "advanced" elements in pleasures and aversions.

Subjects were asked to list pleasures and aversions actually experienced, and pleasures and aversions based on their "innermost fantasies." A 7-point rating scale was developed to rate "primitive" and "advanced" elements in these pleasure-aversion responses. The "primitive" pole of the scale was keyed with the phrase "gut-level experiencing" and the "advanced" pole with "detached objective thinking." Reality Pleasure, Fantasy Pleasure, Reality Aversive, Fantasy Aversive, and Total scores were derived by having trained raters rate each subject's response with the 7-point rating scale. In Study 1, 25 females and 25 males provided pleasure-aversion responses and the data analyzed in a mixed 2 (male-female) x 2 (reality-fantasy) x 2 (pleasure-aversive) ANOVA. The most important finding was a highly significant reality-fantasy x pleasure-aversive interaction: subjects tended to "progress" (give more advanced responses) going from reality to fantasy in their pleasure responses, while exactly the opposite occurred with the aversive responses. Also, as predicted, reality aversive responses tended to be more "advanced" than reality pleasure responses. Study 2 was similar in design, but several additional personality measures were administered to assess the construct validity of the pleasure-aversion scores. As in Study l, the reality-fantasy x pleasure-aversive interaction was highly significant and again reflected a pattern of "progression" going from reality to fantasy for pleasure responses and "regression" for aversive responses. The correlation analysis also produced several interesting findings with sex serving as a major moderator variable.

Adsorption of cellulase from Trichoderma reesei on cellulose and lignacious residue in wood pretreated by dilute sulfuric acid with explosive decompression.

The adsorption of cellulase on cellulose and a lignacious residue was examined by using cellulase from Trichoderma reesei, hardwood pretreated by dilute sulfuric acid under high pressure, and a lignacious residue prepared by a complete enzymatic hydrolysis of the pretreated wood. A significant amount of cellulase was found to adsorb on the lignacious residue during the hydrolysis of the pretreated wood. Hence, the adsorption of enzyme on the lignacious residue as well as cellulose must be taken into account in the development of the hydrolysis kinetics. It was found that the adsorption of enzyme on cellulose and on the lignacious residue could be represented by Langmuir type isotherms. The data show that the pretreatment at a higher temperature results in more enzyme adsorption on the cellulose fraction and less on the lignacious residue fraction. The relationship between the hydrolysis rate and the amount of enzyme adsorbed is discussed.