Willingness to vaccinate children against COVID-19 declined during the pandemic.

OBJECTIVES: To document the level of vaccine hesitancy in caregivers' of children younger than 12 years of age over the course of the pandemic in Pediatric Emergency Departments (ED). Study design Ongoing multicenter, cross-sectional survey of caregivers presenting to 19 pediatric EDs in the USA, Canada, Israel, and Switzerland during first months of the pandemic (phase1), when vaccines were approved for adults (phase2) and most recently when vaccines were approved for children (phase3). RESULTS: Willingness to vaccinate rate declined over the study period (59.7%, 56.1% and 52.1% in the three phases). Caregivers who are fully vaccinated, who have higher education, and those worried their child had COVID-19 upon arrival to the ED, were more likely to plan to vaccinate in all three phases. Mothers were less likely to vaccinate early in the pandemic, but this hesitancy attenuated in later phases. Older caregivers were more willing to vaccinate, and caregivers of older children were less likely to vaccinate their children in phase 3. During the last phase, willingness to vaccinate was lowest in those who had a primary care provider but did not rely on their advice for medical decisions (34%). Those with no primary care provider and those who do and rely on their medical advice, had similar rates of willingness to vaccinate (55.1% and 52.1%, respectively). CONCLUSIONS: COVID-19 vaccine hesitancy is widespread and growing over time, and public health measures should further try to leverage identified factors associated with hesitancy in order to enhance vaccination rates among children.

Factors associated with unvaccinated caregivers who plan to vaccinate their children.

Vaccine hesitancy is complex and a threat to global public health during the ongoing COVID-19 pandemic. Our objective was to determine factors associated with caregivers' willingness to vaccinate children despite not being immunized themselves against COVID-19. The International COVID-19 Parental Attitude Study (COVIPAS), a multinational cohort study, recruited caregivers of children 0-18 years old in 21 Emergency Departments (EDs) in USA, Canada, Israel, and Switzerland during November-December 2021. Of a total of 4536 caregivers who completed the survey, 882 (19.4%) were unvaccinated, and 62 (7.0%) of the unvaccinated planned to vaccinate their children. Unvaccinated caregivers with children that had their childhood vaccines up-to-date (OR 3.03 (1.36, 8.09), p = 0.01), and those very worried their child has COVID-19 in the ED (OR 3.11 (1.44, 6.34), p < 0.01) were much more likely to plan to immunize their children. Primary care providers and public health agencies should not assume that unvaccinated parents will not vaccinate their children. Determining child's vaccination status and parental level of concern about COVID-19 may help identify caregivers who are open to give their children the vaccine.

Longitudinal changes in home-based arts engagement during and following the first national lockdown due to the COVID-19 pandemic in the UK.

AIMS: This study aimed to examine potential heterogeneity in longitudinal changes in home-based arts engagement during the first national lockdown and following gradual easing of restrictions in the UK. Furthermore, it sought to explore factors that were associated with patterns of longitudinal changes in home-based arts engagement. METHOD: Data were from the UCL COVID-19 Social Study. The analytical sample consisted of 29,147 adults in the UK who were followed up for 22 weeks from 21 March to 21 August 2020. Data were analysed using growth mixture models. RESULTS: Our analyses identified five classes of growth trajectories. There were two stable classes showing little change in arts engagement over time (64.4% in total), two classes showing initial increases in arts engagement followed by declines as restrictions were eased (29.8%), and one class showing slight declines during strict lockdown followed by an increase in arts engagement after the easing of restrictions (5.9%). A range of factors were found to be associated with class membership of these arts engagement trajectories, such as age, gender, education, income, employment status, and health. CONCLUSION: There is substantial heterogeneity in longitudinal changes in home-based arts engagement. For participants whose engagement changed over time, growth trajectories of arts engagement were related to changes in lockdown measures. These findings suggest that some individuals may have drawn on the arts when they needed them the most, such as during the strict lockdown period, even if they usually had lower levels of arts engagement before the pandemic. Overall, our results indicate the importance of promoting arts engagement during pandemics and periods of lockdown as part of public health campaigns.

Clinical and anatomopathological features of eosinophilic oesophagitis in children and adults.

INTRODUCTION: Eosinophilic oesophagitis (EoE) is a chronic clinical-pathological disorder with an immunological basis characterised by symptoms of oesophageal dysfunction and, histologically, eosinophilic inflammation. OBJECTIVE: To evaluate the clinical characteristics and differences in children and adults diagnosed with EoE in a tertiary level hospital. METHOD: Descriptive, retrospective and cross-sectional study. We randomly selected 40 children and 40 adults diagnosed with EoE between 2009 and 2016. The patient characteristics were analysed by means of epidemiological, clinical, diagnostic and therapeutic variables. RESULTS: The average age at diagnosis was 10 years (children) and 34 years (adults), with a higher frequency in males. The majority were sensitised to aeroallergens (77.5% children vs. 82.5% adults) and foods (75% children vs. 82.5% adults). Statistically significant differences were detected in sensitisation to fruits (p=0.007) and grains (p<0.001). Differences were observed in impaction (22.5% children vs. 82.5% adults), dysphagia (42.5% children vs. 77.5% adults) and abdominal pain (25% children vs. 7.5% adults). Endoscopy showed that children had a higher frequency of exudates (92.5%) and adults, trachealisation (50% vs. 5%) and stenosis (17.5% vs. 2.5%). Statistically significant differences were found in treatment with topical corticosteroids (30% children vs. 77.5% adults), with a variable positive response. 77.5% of the patients received elimination diets. CONCLUSIONS: Statistically significant differences were observed between the paediatric and adult populations in the food sensitisation profiles, clinical manifestations, endoscopic findings and treatments received. This is a complex pathology that calls for a multidisciplinary team and would require new non-invasive techniques to facilitate its management.

Oral immunotherapy for food allergy: A Spanish guideline. Immunotherapy egg and milk Spanish guide (items guide). Part I: Cow milk and egg oral immunotherapy: Introduction, methodology, rationale, current state, indications contraindications and oral immunotherapy build-up phase.

INTRODUCTION: Cow's milk and egg are the most frequent causes of food allergy in the first years of life. Treatments such as oral immunotherapy (OIT) have been investigated as an alternative to avoidance diets. No clinical practice guides on the management of OIT with milk and egg are currently available. OBJECTIVES: To develop a clinical guide on OIT based on the available scientific evidence and the opinions of experts. METHODS: A review was made of studies published in the period between 1984 and June 2016, Doctoral Theses published in Spain, and summaries of communications at congresses (SEAIC, SEICAP, EAACI, AAAAI), with evaluation of the opinion consensus established by a group of experts pertaining to the scientific societies SEICAP and SEAIC. RESULTS: Recommendations have been established regarding the indications, requirements and practical aspects of the different phases of OIT, as well as special protocols for patients at high risk of suffering adverse reactions. CONCLUSIONS: A clinical practice guide is presented for the management of OIT with milk and egg, based on the opinion consensus of Spanish experts.

Oral immunotherapy for food allergy: A Spanish guideline. Egg and milk immunotherapy Spanish guide (ITEMS GUIDE). Part 2: Maintenance phase of cow milk (CM) and egg oral immunotherapy (OIT), special treatment dosing schedules. Models of dosing schedules of OIT with CM and EGG.

INTRODUCTION: Cow's milk and egg are the most frequent causes of food allergy in the first years of life. Treatments such as oral immunotherapy (OIT) have been investigated as an alternative to avoidance diets. No clinical practice guides on the management of OIT with milk and egg are currently available. OBJECTIVES: To develop a clinical guide on OIT based on the available scientific evidence and the opinions of experts. METHODS: A review was made of studies published in the period between 1984 and June 2016, Doctoral Theses published in Spain, and summaries of communications at congresses (SEAIC, SEICAP, EAACI, AAAAI), with evaluation of the opinion consensus established by a group of experts pertaining to the scientific societies SEICAP and SEAIC. RESULTS: Recommendations have been established regarding the indications, requirements and practical aspects of the different phases of OIT, as well as special protocols for patients at high risk of suffering adverse reactions. CONCLUSIONS: A clinical practice guide is presented for the management of OIT with milk and egg, based on the opinion consensus of Spanish experts.

Oral Immunotherapy for Food Allergy: A Spanish Guideline. Immunotherapy Egg and Milk Spanish Guide (ITEMS Guide). Part I: Cow Milk and Egg Oral Immunotherapy: Introduction, Methodology, Rationale, Current State, Indications, Contraindications, and Oral Immunotherapy Build-up Phase.

BACKGROUND AND OBJECTIVE: Cow milk and egg are the most frequent causes of food allergy in the first years of life. Oral immunotherapy (OIT) has been investigated as an alternative to avoidance diets. No clinical practice guidelines on the management of OIT with milk and egg are currently available. Objectives: To develop clinical guidelines for OIT based on available scientific evidence and the opinions of experts. METHODS: A review was made of studies published between 1984 and June 2016, doctoral theses published in Spain, summaries of communications at scientific meetings (SEAIC, SEICAP, EAACI, and AAAAI), and the consensus of opinion established by a group of experts from the scientific societies SEICAP and SEAIC. RESULTS: Recommendations were established regarding the indications, requirements and practical aspects of the different phases of OIT, as well as special protocols for patients at high risk of adverse reactions. CONCLUSIONS: Clinical practice guidelines based on the consensus reached between Spanish experts are presented for the management of OIT with milk and egg.

Oral Immunotherapy for Food Allergy: A Spanish Guideline. Egg and Milk Immunotherapy Spanish Guide (ITEMS GUIDE). Part II: Maintenance Phase of Cow Milk (CM) and Egg Oral Immunotherapy (OIT), Special Treatment Dosing Schedules. Models of Dosing Schedules of OIT With CM and Egg.

BACKGROUND AND OBJECTIVE: Cow milk and egg are the most frequent causes of food allergy in the first years of life. Oral immunotherapy (OIT) has been investigated as an alternative to avoidance diets. No clinical practice guidelines on the management of OIT with milk and egg are currently available. Objectives: To develop clinical guidelines for OIT based on available scientific evidence and the opinions of experts. METHODS: A review was made of studies published between 1984 and June 2016, doctoral theses published in Spain, summaries of communications at scientific meetings (SEAIC, SEICAP, EAACI, and AAAAI), and the consensus of opinion established by a group of experts from the scientific societies SEICAP and SEAIC. RESULTS: Recommendations were established regarding the indications, requirements and practical aspects of the different phases of OIT, as well as special protocols for patients at high risk of adverse reactions. CONCLUSIONS: Clinical practice guidelines based on the consensus reached between Spanish experts are presented for the management of OIT with milk and egg.

Using biochemical markers to assess the effects of imposed temperature stress on freshwater decapod crustaceans: Cherax quadricarinatus as a test case.

The effects of thermal stress can impact negatively on the abundance and distribution of temperature-sensitive species, particularly freshwater crustaceans. This study investigated the effects of thermal stress on physiological and biochemical parameters at five treatment temperatures resulting in minimal (25 °C), moderate (27, 29 °C) or severe (31, 33 °C) thermal stress in the common tropical freshwater crayfish Cherax quadricarinatus. The aim was to develop a suite of stress-sensitive assays to use on threatened populations of freshwater crustaceans, particularly those restricted to cooler temperatures and only found in high altitude refugia. Significant increases in indicators of oxidative and metabolic stress were observed at 29 °C and were elevated further at 33 °C. After a 50-day acclimation to an imposed temperature stress, significant changes in the level of total glutathione, total lipids, muscular protein, total haemocyte count, lipid peroxidation and protein carbonyls were observed between treatments while superoxide dismutase activity and haemolymph protein concentrations did not change. The data provided proof of concept that measuring key biochemical responses to high temperature can provide a means of contrasting the level of thermal stress experienced between individuals of the same species adapted to different temperatures. The methods developed are expected to be of use in research on wild populations of other freshwater poikilothermic organisms, particularly those susceptible to increased environmental temperatures associated with climate change.

Position document: IgE-mediated allergy to egg protein.

Egg is the food that most often causes allergy in young Spanish children, with an incidence of 2.4-2.6% in the first 2 years of life. The prevalence of sensitisation and allergy to egg is greater in children with allergy to cow's milk and in those suffering atopic dermatitis. The protein component from egg white is the cause of the allergic response in child. The major allergens in egg white are ovomucoid and ovalbumin. Most of the allergic reactions affect the skin, followed by gastrointestinal and respiratory systems. Egg allergy is one of the most common causes of severe anaphylaxis. The diagnosis of egg allergy is based on the existence of a suggestive clinical history, a positive allergy study and the subsequent application of controlled exposure testing, which represents the gold standard for confirming the diagnosis. The treatment of egg allergy is based on the avoidance of egg protein intake. A subgroup of egg-allergic patients are tolerant to cooked egg. In these cases, only uncooked egg must necessarily be avoided. Maintaining a diet with strict egg avoidance is difficult, and transgressions are relatively common. The patient, family, and school environment should receive education and training in the avoidance of egg and in the management of possible allergic reactions. With an avoidance diet, up to 15-20% of children will remain allergic and the severity of the reactions will increase over the years. In these more severe cases of egg-allergy, it becomes more difficult to adhere to the avoidance diet over the years, with a significant decrease in patient quality of life. Oral tolerance induction can be regarded as a therapeutic option for IgE-mediated egg allergy. The anti-IgE, omalizumab, might become another genuine therapeutic option for food allergy, not only to prevent allergic reactions after a contact with egg, but also as a complementary treatment to oral tolerance induction for egg allergy, with the purpose of reducing adverse reactions. The administration of influenza vaccine to children with egg allergy is safe in children that do not manifest severe reactions after egg intake, and in children who tolerate cooked egg. The triple viral vaccine (MMR) can be given to egg-allergic children in their usual vaccination centre, with no added risk. Different medicinal products can be formulated with egg proteins, and therefore should be avoided in children with egg allergy.

The management of acute musculoskeletal pain.

Musculoskeletal pain is a common presentation in military patients. If not managed effectively it can have a detrimental effect on both the individual and the ship/unit. This article aims to examine how to thoroughly assess a military patient presenting with acute musculoskeletal pain; to provide the practitioner with a framework for effective pain history taking, and to help identify and exclude rare but serious causes of pain - 'red and yellow flag concepts'. Key management steps and appropriate interventions for managing acute, benign musculoskeletal pain are discussed and related to the varying environmients where the patient may be encountered.

Open Air Laboratories (OPAL): a community-driven research programme.

OPAL is an English national programme that takes scientists into the community to investigate environmental issues. Biological monitoring plays a pivotal role covering topics of: i) soil and earthworms; ii) air, lichens and tar spot on sycamore; iii) water and aquatic invertebrates; iv) biodiversity and hedgerows; v) climate, clouds and thermal comfort. Each survey has been developed by an inter-disciplinary team and tested by voluntary, statutory and community sectors. Data are submitted via the web and instantly mapped. Preliminary results are presented, together with a discussion on data quality and uncertainty. Communities also investigate local pollution issues, ranging from nitrogen deposition on heathlands to traffic emissions on roadside vegetation. Over 200,000 people have participated so far, including over 1000 schools and 1000 voluntary groups. Benefits include a substantial, growing database on biodiversity and habitat condition, much from previously unsampled sites particularly in urban areas, and a more engaged public.

Oral desensitization as a useful treatment in 2-year-old children with cow's milk allergy.

BACKGROUND: Limited published evidence shows oral desensitization to be a potential intervention option for cow's milk protein (CMPs) allergy. OBJECTIVE: The aim of this study was to evaluate the safety and efficacy of oral desensitization in 2-year-old children with cow's milk allergy, as a treatment alternative to elimination diet. METHODS: A total of 60 children aged 24-36 months with IgE-mediated allergy to CMPs were included in this multi-center study and were randomized into two groups. Thirty children (group A: treatment group) began oral desensitization immediately, whereas the remaining 30 (group B: control group) were kept on a milk-free diet and followed-up for 1 year. RESULTS: After 1-year follow-up period, 90% of the children in group A had become completely tolerant vs. 23% of the children in group B. In group A, cow's milk skin reactivity and serum-specific IgE to milk and casein decreased significantly from the initial assessment, whereas group B showed no significant change after 1 year of follow-up. Twenty-four patients (80%) developed some reaction during the treatment period: 14 children developed moderate reaction (47%) and 10 mild reaction (33%). The most common manifestations were urticaria-angioedema, followed by cough. CONCLUSIONS AND CLINICAL RELEVANCE: In this study, oral desensitization was found to be effective in a significant percentage of 2-year-old children with cow's milk allergy. Oral desensitization appears to be efficacious as an alternative to elimination diet in the treatment of 2-year-old children with cow's milk allergy. The side-effect profile appears acceptable but requires further study.

Evaluation of an extensively hydrolysed casein formula (Damira 2000) in children with allergy to cow's milk proteins.

OBJECTIVE: To assess the allergenic capacity of a new extensively hydrolysed casein formula (Damira 2000) in vivo in children with allergy to cow's milk, and to conduct an immunochemical evaluation of the product. PATIENTS AND METHODS: The study comprised 67 children (1 month-7 years) with allergy to cow's milk proteins (ACMP). Skin testing was made with whole milk, milk formula for infants, the study hydrolysate and the milk fractions (alpha-lactoalbumin, beta-lactoglobulin and casein). Specific IgE against these allergens, and oral provocation test were also performed. Immunochemical evaluation of the product was carried out with gel filtration chromatography, 4-15% acrylamide gradient gel electrophoresis, specific IgE quantification versus the casein hydrolysate and a study of its allergenic potency. RESULTS: The hydrolysate was tolerated by 66 of the 67 patients (98.5%) with ACMP. Biochemical analysis of the product confirmed the absence of traces of whole milk proteins. Specific IgE against the hydrolysate proved negative in all cases, and it was unable to inhibit FEIA even at concentrations 10 times greater than those used in the whole milk inhibition control. Likewise, no immunoblotting inhibition was recorded. CONCLUSIONS: The new extensively hydrolysed casein product is safe and well tolerated by most children with ACMP. However, as with other extensive hydrolysates, some highly sensitised patients may present clinical manifestations. Controlled tolerance testing is therefore advised, under specialised medical supervision.

Allergic proctocolitis, food-induced enterocolitis: immune mechanisms, diagnosis and treatment.

The term food allergy refers to the immune reaction (mediated by IgE or otherwise) that develops in response to the ingestion of a concrete type of food. Among the different potential manifestations of an allergic reaction, those exclusively affecting the gastrointestinal system are described. In recent years, the study of non-IgE-mediated food allergy has grown in relevance. These disorders are almost always of a transient nature, inherent to (though not exclusive of) nursing infants, and with gastrointestinal symptoms that may have variable repercussions upon the nutritional state of the patient. The prevalence of such reactions is not known, though some studies report that up to 60 % of all cases of allergy to cow's milk proteins (CMPs) are due to non-IgE-mediated mechanisms. The latency period between the time of ingestion and the appearance of the first clinical manifestations is greater than in the case of IgE-mediated reactions, and the underlying immunopathological mechanism has not been clearly established although it is accepted that T cell mediation is involved. The gastrointestinal problems derived from these delayed or chronic reactions comprise allergic proctocolitis, enterocolitis and food protein enteropathies. These digestive disorders tend to appear in the first months of life, and are of a progressive and generally self-limiting nature, with resolution at about two years of age. The most commonly implicated food is milk and, in our setting, there have also been reports implicating fish, egg and rice although such reactions can be triggered by any protein introduced into the infant diet. These manifestations disappear after removing the causal protein from the diet. When the causal proteins are CMPs, a highly hydrolysed infant formula is supplied as substitute, and if the latter is not tolerated, an elemental amino acid-based formula is prescribed.

The predictive value of specific immunoglobulin E levels in serum for the outcome of the development of tolerance in cow's milk allergy.

BACKGROUND: Immunoglobulin E-mediated allergy to cow's milk protein (CMP) tends to subside over years of follow-up. The gold standard for detecting such allergy has been the oral challenge test. The development of some other test for determining the correct timing of the oral challenge test would avoid unnecessary patient discomfort. The aim of this study was to determine whether monitoring cow's milk (CM) specific IgE levels over time can be used as a predictor for determining when patients develop clinical tolerance. METHODS: A prospective 4-year follow-up study was made of 170 patients with IgE-mediated allergy to CMP, involving periodic evaluations (12, 18, 24, 36 and 48 months) with the determination of casein and CM specific IgE on each visit, along with CM challenge testing. ROC curves were used to analyse the sensitivity, specificity and predictive values of the casein and CM specific IgE levels versus the challenge test outcomes at the different moments of follow-up. RESULTS: In the course of follow-up, 140 infants (82 %) became tolerant. Specific IgE levels to CM: 2.58, 2.5, 2.7, 2.26, 5 kU(A)/l and to casein: 0.97, 1.22, 3, 2.39, 2.73 kU(A)/l, respectively, predicted clinical reactivity (greatest diagnostic efficiency values) at the different analysed moments of follow-up (12, 18, 24, 36 and 48 months). CONCLUSIONS: Quantification of CMP specific IgE is a useful test for diagnosing symptomatic allergy to CM in the paediatric population, and could eliminate the need to perform oral challenges tests in a significant number of children.

Markers of oxidative stress in the skeletal muscle of patients on haemodialysis.

BACKGROUND: Increased oxidative stress may play a role in morbidity and mortality of patients with renal failure. Most studies have examined serum markers of oxidation, but it is unclear whether oxidative stress is involved in skeletal muscle atrophy. METHODS: This study examined markers of oxidative stress in the skeletal muscle of 10 haemodialysed patients and 10 control subjects. Biopsies from the quadriceps femoris were analysed for reduced and oxidized glutathione, protein thiols, malonaldehyde and heat shock proteins (HSP27, HSP60 and HSP70), superoxide dismutase and catalase activities. A novel microdialysis procedure was used to examine hydroxyl radical activity in the interstitial fluid of the tibialis anterior. RESULTS: Patients had muscle atrophy with a reduced diameter of both type I and II fibres (by 15 and 20%, respectively). Muscle microdialysates contained 2,3- and 2,5-dihydroxybenzoates formed from salicylate indicating hydroxyl radical activity, with no differences between patients and control subjects. Muscle protein thiol and oxidized glutathione contents were unchanged in patients, but malonaldehyde content was reduced. In contrast, total muscle glutathione and heat shock protein contents were increased. Muscle superoxide dismutase activity was unchanged, but catalase activity was reduced in patients. CONCLUSIONS: The muscle of patients undergoing haemodialysis undergoes some adaptive responses in total glutathione content, heat shock protein content and catalase activity that are potentially related to chronic oxidative stress. However, there is no evidence of gross oxidation, nor any clear relationship between oxidative stress and muscle fibre atrophy, arguing against a direct role of oxidants in the degenerative processes.

Evaluation of paediatric tolerance to an extract of Alternaria alternata under two treatment regimes. A multicentre study.

In order to evaluate the efficacy and safety of an extract of Alternaria alternata in a paediatric population, a two phase study plan has been elaborated that in the first place consists of a retrospective analysis of tolerance under the standard treatment regimes used by the clinical groups involved. This was achieved by analysing the records of 94 patients that have been treated with this extract, these being consecutive patients included at 7 clinics over a period of 6 months. Two regimes were used: a conventional short regime of 7 doses and a cluster regime. Under neither of these two regimes were any serious reactions registered. The percentage of local reactions was significantly greater using the short conventional regime than with the cluster regime (1.9% and 0.4% respectively, p = .035). In contrast, no significant differences were observed with respect to the systemic reactions (0.5% and 1.2%), these percentages also being similar to those registered with other extracts in which identical regimes have been used. In conclusion, we can confirm that a very satisfactory tolerance profile was observed, with the advantage that through using shorter regimes than the conventional regime of 13 doses, a considerable saving is made both in the number of visits and the doses necessary to reach the maintenance dose.

Calcineurin inhibitors and proximal renal tubular injury in renal transplant patients with proteinuria and chronic allograft nephropathy.

BACKGROUND: Chronic allograft nephropathy (CAN) is commonly associated with proteinuria. In native nephropathies, proteinuria is linked with proximal renal tubular damage. This study uses regression analysis to link proteinuria with urinary N-acetyl-beta-d-glucosaminidase (NAG) as a marker of tubular injury or hyperfunction in renal transplant patients. METHODS: Proteinuria and urinary NAG were measured and regression analysis applied in 105 transplant patients (42 with CAN). Most were receiving calcineurin inhibitor-based immunosuppression (cyclosporine, n=60; tacrolimus, n=26; and neither drug, n=19). Patients with native nephropathies (n=96) and volunteers (n=21) were also studied. RESULTS: Urinary NAG increased with increasing proteinuria. However, patients taking calcineurin inhibitors had higher urinary NAG at any level of urinary protein than those on alternative therapy, or in native nephropathies. CONCLUSIONS: In groups of transplant patients taking different immunosuppressive regimens, regression analysis of urinary NAG against urinary protein can identify the separate effects of drug-related tubular injury or hyperfunction from that of proteinuria.

Abnormal mitochondrial function and muscle wasting, but normal contractile efficiency, in haemodialysed patients studied non-invasively in vivo.

BACKGROUND: Muscle dysfunction, which contributes to morbidity in patients on haemodialysis, has several manifestations and a number of possible causes. We applied the non-invasive techniques of (31)P-magnetic resonance spectroscopy ((31)P-MRS), magnetic resonance imaging (MRI) and near-infrared spectroscopy (NIRS) to calf muscle of dialysed patients to define the abnormalities in muscle cross-sectional area (CSA), contractile efficiency, mitochondrial function and vascular O(2) supply. METHODS: We performed (31)P-MRS/NIRS/MRI studies on the lateral gastrocnemius during isometric plantarflexion and recovery in 23 male patients on haemodialysis (age 24-71 years; haemoglobin 9.9-14.2 g/dl; bicarbonate 17-30 mmol/l; urea reduction ratio 53-77%; parathyroid hormone 1-95 U/l) and 15 male controls (age 29-71 years). To understand the relationships between calf CSA and body mass we also performed MRI only in a further six male patients and 18 male controls. RESULTS: In patients, exercise duration was 30+/-11% lower than in controls. Muscle CSA was lower by 26+/-5%, but contractile efficiency (force/CSA/ATP turnover) was normal. Slowing of post-exercise phosphocreatine (PCr) recovery implied a 22+/-5% defect in effective 'mitochondrial capacity'. That PCr recovery was slow relative to NIRS recovery suggests that this is largely an intrinsic mitochondrial problem (not the result of impaired O(2) supply), one which, furthermore, correlated with CSA. Urea reduction ratio showed a negative correlation with body mass and CSA, but none with PCr rate constant. CONCLUSIONS: The relationships to urea reduction ratio reflect the effect of muscle mass on dialysis efficiency, rather than direct effects on muscle CSA or metabolism. The relationship between PCr recovery and calf CSA suggests a role for the mitochondrial defect, whatever its cause, in the development of muscle wasting, although a common cause (e.g. physical inactivity) for both abnormalities cannot be ruled out.