Histamine, mast cell tryptase and post-exercise hypotension in healthy and collapsed marathon runners.

PURPOSE: Heat stress exacerbates post-exercise hypotension (PEH) and cardiovascular disturbances from elevated body temperature may contribute to exertion-related incapacity. Mast cell degranulation and muscle mass are possible modifiers, though these hypotheses lack practical evidence. This study had three aims: (1) to characterise pre-post-responses in histamine and mast cell tryptase (MCT), (2) to investigate relationships between whole body muscle mass (WBMM) and changes in blood pressure post-marathon, (3) to identify any differences in incapacitated runners. METHODS: 24 recreational runners were recruited and successfully completed the 2019 Brighton Marathon (COMPLETION). WBMM was measured at baseline. A further eight participants were recruited from incapacitated runners (COLLAPSE). Histamine, MCT, blood pressure, heart rate, body temperature and echocardiographic measures were taken before and after exercise (COMPLETION) and upon incapacitation (COLLAPSE). RESULTS: In completion, MCT increased by nearly 50% from baseline (p = 0.0049), whereas histamine and body temperature did not vary (p > 0.946). Systolic (SBP), diastolic (DBP) and mean (MAP) arterial blood pressures and systemic vascular resistance (SVR) declined (p < 0.019). WBMM negatively correlated with Δ SBP (r = - 0.43, p = 0.046). For collapse versus completion, there were significant elevations in MCT (1.77 ± 0.25 µg/L vs 1.18 ± 0.43 µg/L, p = 0.001) and body temperature (39.8 ± 1.3 °C vs 36.2 ± 0.8 °C, p < 0.0001) with a non-significant rise in histamine (9.6 ± 17.9 µg/L vs 13.7 ± 33.9 µg/L, p = 0.107) and significantly lower MAP, DBP and SVR (p < 0.033). CONCLUSION: These data support the hypothesis that mast cell degranulation is a vasodilatory mechanism underlying PEH and exercise associated collapse. The magnitude of PEH is inversely proportional to the muscle mass and enhanced by concomitant body heating.

Cheiroarthropathy and tendinopathy in diabetes.

Joint problems commonly occur in people with diabetes. Cheiroarthropathy affects the hands and results in painless limited finger joint extension, appearing to be associated with longer diabetes duration and the presence of microvascular complications. The prevalence of cheiroarthropathy seems to be falling, perhaps as a result of improvements in glycaemic management. Non-enzymatic glycation of collagen results in abnormally crosslinked protein resistant to degradation with subsequent increased build-up of collagen in joints. The management of cheiroarthropathy is predominantly conservative, with occupational and hand therapy at the forefront. Tendinopathy is more common in people with diabetes than those without, and is associated with obesity and insulin resistance. As with cheiroarthropathy, the exact causative mechanism of tendinopathy in diabetes is not known, but may be linked to inflammation, apoptosis and increased vascularity of affected tendons, driven by hyperinsulinaemia. Local fat pads have also been suggested to play a role in the pathogenesis of tendinopathy.

Risk factors for heat illness among British soldiers in the hot Collective Training Environment.

BACKGROUND: Heat illness is a preventable disorder in military populations. Measures that protect vulnerable individuals and contribute to effective Immediate Treatment may reduce the impact of heat illness, but depend upon adequate understanding and awareness among Commanders and their troops. OBJECTIVE: To assess risk factors for heat illness in British soldiers deployed to the hot Collective Training Environment (CTE) and to explore awareness of Immediate Treatment responses. METHODS: An anonymous questionnaire was distributed to British soldiers deployed in the hot CTEs of Kenya and Canada. Responses were analysed to determine the prevalence of individual (Intrinsic) and Command-practice (Extrinsic) risk factors for heat illness and the self-reported awareness of key Immediate Treatment priorities (recognition, first aid and casualty evacuation). RESULTS: The prevalence of Intrinsic risk factors was relatively low in comparison with Extrinsic risk factors. The majority of respondents were aware of key Immediate Treatment responses. The most frequently reported factors in each domain were increased risk by body composition scoring, inadequate time for heat acclimatisation and insufficient briefing about casualty evacuation. CONCLUSIONS: Novel data on the distribution and scale of risk factors for heat illness are presented. A collective approach to risk reduction by the accumulation of 'marginal gains' is proposed for the UK military. This should focus on limiting Intrinsic risk factors before deployment, reducing Extrinsic factors during training and promoting timely Immediate Treatment responses within the hot CTE.

Assessment of salivary cortisol dynamics in an infantry training exercise: a pilot study.

INTRODUCTION: Measuring cortisol during military training offers insights into physiological responses to stress. We attempted precisely timed, cortisol awakening response (CAR) and pre-sleep cortisol (PSC), and diurnal slope (peak morning minus evening cortisol), during a British Army exercise. We aimed to understand cortisol dynamics and evaluate the feasibility of CAR and PSC in this environment. METHOD: Setting: high-intensity, 10-day infantry exercise. Participants: regular infantry soldiers exercising (EX, n=25) or headquarters-based (HQ, n=6). Participants undertook PSC and WAKE and WAKE+30 min samples after 1-2 days, 5-6 days and 9-10 days. Wrist-worn GENEActiv accelerometers were used to assess sleep duration in EX only. Samples taken ±15 min from prespecified time points were deemed adherent. Validated questionnaires were used to measure resilience and perceived stress. Cortisol and cortisone were measured simultaneously by liquid chromatography tandem mass spectrometry. RESULTS: From adherent participants' samples, CAR was positive and tended to decrease as the exercise progressed. From all available data, HQ demonstrated greater diurnal slope than EX (F=7.68, p=0.02), reflecting higher morning cortisol (F=4.72, p=0.038) and lower PSC (p=0.04). No differences were seen in cortisol:cortisone ratio. 26.1% of CAR samples were adherent, with moderately strong associations between adherence and stress (r=0.41, p=0.009) but no association between adherence and day of exercise (χ2=0.27, p=0.8), sleep duration (r=-0.112, p=0.43) or resilience (r=-0.79, p=0.75). Test-retest reliability ratings for CAR were Cronbach's α of 0.48, -11.7 and 0.34 for the beginning, middle and end of the exercise, respectively. CONCLUSIONS: We observed a reduction in morning cortisol and decreased diurnal slope during a high-intensity military exercise, compared with the HQ comparator cohort in whom diurnal slope was preserved. A carefully timed CAR was not feasible in this setting.

Reflex syncope in the UK Armed Forces.

INTRODUCTION: Reflex syncope is the most common subtype of syncope and, despite not being associated with increased mortality, often results in significant morbidity and costly diagnostics. Reflex syncope can be of concern for certain occupational groups and may be exacerbated by some occupations. Reflex syncope in the military is anecdotally common but the extent in the UK Armed Forces (UKAF) is unknown. The aim of this study was to assess the incidence and prevalence of reflex syncope in the UKAF. METHODS: A retrospective search of the Defence Medical Information Capability Programme using prespecified read-codes was performed at defence primary healthcare centres over the period of 1 January 2019 to 1 January 2020. Data were obtained on 76 103 service personnel (SP) (53% of the UKAF). RESULTS: The overall syncope case rate for the UKAF was 10.5 per 1000 person-years (p-yrs). In comparing services there was a significantly increased risk of syncope in the British Army (10.7 per 1000 p-yrs) compared with the Royal Air Force (8.6 per 1000 p-yrs) (p=0.0365), SP who served overseas (16.7 per 1000 p-yrs) in comparison with UK medical centres (10.3 per 1000 p-yrs) (p<0.0001), and British Army units that regularly took part in State Ceremonial and Public Duties (15.8 per 1000 p-yrs vs 10.2 per 1000 p-yrs) (p=0.0035). Army training units conferred a significantly reduced risk of syncope (p<0.0001). CONCLUSIONS: These data are the first to define the incidence and prevalence of syncope in the UKAF. Orthostasis and heat are probable triggers, although recruits are potentially protected. These data offer opportunities to improve the health and well-being of SP, with economic, logistical and reputational benefits for the UKAF. Further research to identify personnel at risk of future syncopal events may allow for targeted use of countermeasures.

Risk factors for reflex syncope in the British Army.

INTRODUCTION: Reflex syncope in the UK Armed Forces is reportedly higher than comparable militaries and civilian populations and is significantly more common in soldiers who take part in State Ceremonial and Public Duties (SCPD) compared with other British Army service personnel (SP). This study aimed to investigate individual susceptibility factors for syncope in soldiers who regularly take part in SCPD. METHODS: A retrospective cohort study was performed in 200 soldiers who perform SCPD. A questionnaire was undertaken reviewing soldiers' medical history and circumstances of any fainting episodes. A consented review of participants' electronic primary healthcare medical record was also performed. Participants were divided into two groups (syncope, n=80; control, n=120) based on whether they had previously fainted. RESULTS: In the syncope group orthostasis (61%) and heat (35%) were the most common precipitating factors. The most common interventions used by soldiers were to maintain hydration (59%) and purposeful movements (predominantly 'toe wiggling'; 55%). 30% of participants who had previously fainted did not seek definitive medical attention. A history of migraines/headaches was found to increase the risk of reflex syncope (OR 8.880, 1.214-218.8), while a history of antihistamine prescription (OR 0.07144, 0.003671-0.4236), non-white ethnicity (OR 0.03401, 0.0007419-0.3972) and male sex (OR 0.2640, 0.08891-0.6915) were protective. CONCLUSION: This is the first study, in the British Army, to describe, categorise and establish potential risk factors for reflex syncope. Orthostatic-mediated reflex syncope is the most common cause in soldiers who regularly perform SCPD and this is further exacerbated by heat exposure. Soldiers do not use evidence-based methods to avoid reflex syncope. These data could be used to target interventions for SP who have previously fainted or to prevent fainting during SCPD.

Neurobiomarker and body temperature responses to recreational marathon running.

OBJECTIVES: To assess how biomarkers indicating central nervous system insult (neurobiomarkers) vary in peripheral blood with exertional-heat stress from prolonged endurance exercise. DESIGN: Observational study of changes in neuron specific enolase (NSE), S100 calcium-binding protein B (S100ß), Glial Fibrillary Acid Protein (GFAP) and Ubiquitin carboxyl-terminal hydrolase isozyme L1 (UCHL1) at Brighton Marathon 2022. METHODS: In 38 marathoners with in-race core temperature (Tc) monitoring, exposure (High, Intermediate or Low) was classified by cumulative hyperthermia - calculated as area under curve of Time × Tc > 38 °C - and also by running duration (finishing time). Blood was sampled for neurobiomarkers, cortisol and fluid-regulatory stress surrogates, including copeptin and creatinine (at rested baseline; within 30 min of finishing; and at 24 h). RESULTS: Finishing in 236 ±â€¯40 min, runners showed stable GFAP and UCH-L1 across the marathon and next-day. Significant (P < 0.05) increases from baseline were shown post-marathon and at 24 h for S100ß (8.52 [3.65, 22.95] vs 39.0 [26.48, 52.33] vs 80.3 [49.1, 99.7] ng·L-1) and post-marathon only for NSE (3.73 [3.30, 4.32] vs 4.85 [4.45, 5.80] µg·L-1, P < 0.0001). Whilst differential response to hyperthermia was observed for cortisol, copeptin and creatinine, neurobiomarker responses did not vary. Post-marathon, only NSE differed by exercise duration (High vs Low, 5.81 ±â€¯1.77 vs. 4.69 ±â€¯0.73 µg·L-1, adjusted P = 0.0358). CONCLUSIONS: Successful marathon performance did not associate with evidence for substantial neuronal insult. To account for variation in neurobiomarkers with prolonged endurance exercise, factors additional to hyperthermia, such as exercise duration and intensity, should be further investigated.

Heat illness experience at BMH Shaibah, Basra, during Operation TELIC: May-July 2003.

This is an observational study of heat-related illness in UK Service Personnel deployed into summer conditions in Northern Kuwait and Southern Iraq. Among 622 hospitalisations reported during a 9-week period at the historical British Military Hospital, Shaibah, 303 consecutive admissions are reviewed in detail. Several clinical syndromes attributable to thermal stress were observed. These ranged from self-limiting debility to life-threatening failures of homeostasis, with 5.0% developing a critical care requirement. Hyponatraemia was a commonly occurring electrolyte disturbance by which, relative to the local reference range, a majority of heat-attributed admissions were affected. Reductions in measured serum sodium could be profound (<125 mmol/L in 20.1% of all heat-related casualties). Hypokalaemia was observed in half of cases, though only a minority were affected by severely low potassium (<2.5 mmol/L in 4.0%). Despite preventive measures prescribed on hospital discharge, illness and significant biochemical derangements could recur upon return to duties in the heat. We reiterate the need for primary prevention of heat illness wherever possible and importance of early, effective interventions to treat and protect Service Personnel from secondary injury. We also highlight the requirement for comprehensive assessment to inform prognostication and occupational decision-making in relation to extreme climatic heat, including aeromedical evacuation. We draw additional attention to the contribution of psychological factors in select cases and identify research questions to improve understanding of environment-induced incapacitation in general.

Energy at high altitude.

For the military doctor, an understanding of the metabolic effects of high altitude (HA) exposure is highly relevant. This review examines the acute metabolic challenge and subsequent changes in nutritional homeostasis that occur when troops deploy rapidly to HA. Key factors that impact on metabolism include the hypoxic-hypobaric environment, physical exercise and diet. Expected metabolic changes include augmentation of basal metabolic rate (BMR), decreased availability of oxygen in peripheral metabolic tissues, reduction in VO2 max, increased glucose dependency and lactate accumulation during exercise. The metabolic demands of exercise at HA are crucial. Equivalent activity requires greater effort and more energy than it does at sea level. Soldiers working at HA show high energy expenditure and this may exceed energy intake significantly. Energy intake at HA is affected adversely by reduced availability, reduced appetite and changes in endocrine parameters. Energy imbalance and loss of body water result in weight loss, which is extremely common at HA. Loss of fat predominates over loss of fat-free mass. This state resembles starvation and the preferential primary fuel source shifts from carbohydrate towards fat, reducing performance efficiency. However, these adverse effects can be mitigated by increasing energy intake in association with a high carbohydrate ration. Commanders must ensure that individuals are motivated, educated, strongly encouraged and empowered to meet their energy needs in order to maximise mission-effectiveness.

Does vitamin D supplementation prevent SARS-CoV-2 infection in military personnel? Review of the evidence.

For most individuals residing in Northwestern Europe, maintaining replete vitamin D status throughout the year is unlikely without vitamin D supplementation and deficiency remains common. Military studies have investigated the association with vitamin D status, and subsequent supplementation, with the risk of stress fractures particularly during recruit training. The expression of nuclear vitamin D receptors and vitamin D metabolic enzymes in immune cells additionally provides a rationale for the potential role of vitamin D in maintaining immune homeostasis. One particular area of interest has been in the prevention of acute respiratory tract infections (ARTIs). The aims of this review were to consider the evidence of vitamin D supplementation in military populations in the prevention of ARTIs, including SARS-CoV-2 infection and consequent COVID-19 illness. The occupational/organisational importance of reducing transmission of SARS-CoV-2, especially where infected young adults may be asymptomatic, presymptomatic or paucisymptomatic, is also discussed.

A comparative analysis of the encapsulated end-organs of mammalian skeletal muscles and of their sensory nerve endings.

The encapsulated sensory endings of mammalian skeletal muscles are all mechanoreceptors. At the most basic functional level they serve as length sensors (muscle spindle primary and secondary endings), tension sensors (tendon organs), and pressure or vibration sensors (lamellated corpuscles). At a higher functional level, the differing roles of individual muscles in, for example, postural adjustment and locomotion might be expected to be reflected in characteristic complements of the various end-organs, their sensory endings and afferent nerve fibres. This has previously been demonstrated with regard to the number of muscle-spindle capsules; however, information on the other types of end-organ, as well as the complements of primary and secondary endings of the spindles themselves, is sporadic and inconclusive regarding their comparative provision in different muscles. Our general conclusion that muscle-specific variability in the provision of encapsulated sensory endings does exist demonstrates the necessity for the acquisition of more data of this type if we are to understand the underlying adaptive relationships between motor control and the structure and function of skeletal muscle. The present quantitative and comparative analysis of encapsulated muscle afferents is based on teased, silver-impregnated preparations. We begin with a statistical analysis of the number and distribution of muscle-spindle afferents in hind-limb muscles of the cat, particularly tenuissimus. We show that: (i) taking account of the necessity for at least one primary ending to be present, muscles differ significantly in the mean number of additional afferents per spindle capsule; (ii) the frequency of occurrence of spindles with different sensory complements is consistent with a stochastic, rather than deterministic, developmental process; and (iii) notwithstanding the previous finding, there is a differential distribution of spindles intramuscularly such that the more complex ones tend to be located closer to the main divisions of the nerve. Next, based on a sample of tendon organs from several hind-foot muscles of the cat, we demonstrate the existence in at least a large proportion of tendon organs of a structural substrate to account for multiple spike-initiation sites and pacemaker switching, namely the distribution of sensory terminals supplied by the different first-order branches of the Ib afferent to separate, parallel, tendinous compartments of individual tendon organs. We then show that the numbers of spindles, tendon organs and paciniform corpuscles vary independently in a sample of (mainly) hind-foot muscles of the cat. Grouping muscles by anatomical region in the cat indicated the existence of a gradual proximo-distal decline in the overall average size of the afferent complement of muscle spindles from axial through hind limb to intrinsic foot muscles, but with considerable muscle-specific variability. Finally, we present some comparative data on muscle-spindle afferent complements of rat, rabbit and guinea pig, one particularly notable feature being the high incidence of multiple primary endings in the rat.

A case of external ophthalmomyiasis in a deployed U.K. soldier.

Infestation of the eye by larval fly forms (ophthalmomyiasis) is rarely seen in the Western world. We present the case of a 21 year old British soldier who developed external ophthalmomyiasis during an operational tour of southern Afghanistan. This case report and discussion illustrates the potential for ophthalmomyiasis in personnel deployed to this theatre; the possibility of infestation without an identifiable episode of exposure; the importance of proper assessment and follow-up in order to identify sight-threatening complications; and the balance between optimal patient care and the risks inherent to casualty evacuation demanded by modern day stability operations.

The innervation of tandem muscle spindles in the cat neck.

Patterns of innervation were examined in tandem muscle spindles teased from silver-stained muscles of the cat neck. Each tandem spindle was composed of two or more encapsulated receptors linked in series by a shared bag2 fiber. In most tandem spindles, two different types of encapsulation were identified according to differences in their intrafusal fiber content. One type, the b1b2c unit, contained typical bag1, bag2, and chain fibers and was structurally similar to single spindles described in other cat muscles. Each b1b2c unit contained a single primary sensory ending and 1-6 secondary endings. Fusimotor innervation was supplied by many axons. Some fusimotor axons ended in trail ramifications on bag2 and chain fibers, others ended in plates on the bag1 or long chain fiber. The other type of tandem encapsulation, the b2c unit, had only bag2 and chain fibers in its intrafusal fiber bundle. The b2c unit was usually supplied by only one sensory axon that ended on the nucleated part of the intrafusal fiber bundle. This single ending had a more variable terminal morphology than the primary ending in b1b2c units. A few b2c units (3/49) were also supplied by a secondary ending. The fusimotor innervation of the b2c unit was relatively simple. A single pole of the b2c unit was usually supplied by only one to three axons, all ending in trail ramifications. No plate endings were found in b2c units. These morphological specializations suggest that b1b2c and b2c units in tandem spindles differ in both their transductive and fusimotor mechanisms. Thus, the tandem spindle is a specialized structure that may provide additional proprioceptive information beyond that available from single muscle spindles.

Sensory reinnervation of cat peroneus brevis muscle spindles after nerve crush.

Results are presented of examining the postcrush sensory reinnervation of cat peroneus brevis muscle spindles previously investigated physiologically by Hyde and Scott. It is shown that primary and secondary endings were successfully restored in their final form in the early stages of recovery. The primary endings were shorter than normal and had fewer transverse bands; 12% were judged to be hyperinnervated. Some secondary endings showed signs of growth through the primary region apparently designed to establish secondary terminals in the opposite pole. This is compared with the collateral regeneration of intact motor axons in partially denervated muscle. It is concluded that the defects observed in the regenerated sensory endings had no effect on their functional recovery.

Identifications of the intrafusal endings of skeletofusimotor axons in the cat.

Direct identification of the endings of skeletofusimotor (beta) axons has been made in muscle spindles deprived for their gamma innervation by degeneration. Hindlimb muscles were prepared in which 1--5 fast-conducting motor axons were left intact while the rest of the motor supply was cut and allowed to degenerate for a period of 7 days. In 3 experiments a single beta axons survived supplying tenuissimus, and in 2 experiments beta axons were among 4 or 5 surviving axons that supplied superficial lumbrical and abductor digiti quinti medius muscles. Motor endings identified as p1 plates were found in teased, silver preparations of all experimental muscles, a total of 35 such plates being located in 15 spindles. The plates were all supplied to bag1 fibres. The experiments show that if a spindle innervated by a beta axon is deprived of its gamma supply by degeneration the motor endings that remain intact are p1 plates.

The metabolism of exogenous histamine by aortic tissues.

A thin layer chromatographic system is presented for the separation of histamine (H), 1,4-methylhistamine (M), acid metabolites comprising imidazole and methylimidazole acetic acids (A) and N-acetylhistamine (N). The system was applied to separation of the histamine metabolites formed following incubation of rabbit and guinea-pig thoracic aorta segments with labelled histamine. The effects of various agents known to affect histamine uptake, storage and metabolism in vascular tissue were studied on the disposition of histamine metabolites.