Acute Muscle Wasting Research Articles

Acute Skeletal Muscle Wasting is Associated with Prolonged Hospital Stay in Critical Illness with Brain Injury.

Acute muscle wasting is common in critically ill patients, and this can lead to unfavorable clinical outcomes. The aim of this study was to identify factors associated with muscle wasting and to investigate the association between skeletal muscle wasting and prolonged hospital stay in critically ill patients with acute brain injury. This single-center prospective observational study was conducted in critically ill patients with acute brain injury who stayed in the intensive care unit for at least 1week. The rectus femoris cross-sectional area was measured via ultrasound at baseline and a week after the first assessment. Univariate and multivariate logistic regression analyses were performed to identify factors that predicted prolonged hospital stay. A total of 86 patients were included in the study. Their mean age was 49.4 ± 16.9years, 57% were male, and 46.5% had an admission diagnosis of subarachnoid hemorrhage. The percentage change in the rectus femoris cross-sectional area was 15.8% (95% confidence interval [CI] - 19.8% to - 12.0%; p < 0.001), and 57% of all patients had acute muscle wasting. According to the univariate analysis, there was a significant association between prolonged hospital stay and acute muscle wasting (odds ratio [OR] 3.677; 95% CI 1.487-9.043; p = 0.005), mechanical ventilation status (OR 3.600; 95% CI 1.455-8.904; p = 0.006), and Glasgow Coma Scale score (OR 0.888; 95% CI 0.808-0.976; p = 0.014) at intensive care unit admission. The multivariate analysis demonstrated that acute muscle wasting (OR 3.449; 95% CI 1.344-8.853; p = 0.010) was an independent risk factor for prolonged hospital stay. There was considerable muscle wasting in critically ill patients with brain injuries over a 1-week period. Acute muscle wasting was associated with prolonged hospital stay in critically ill patients with acute brain injury.

Acute muscle wasting is associated with poor prognosis in older adults with severe community-acquired pneumonia.

To investigate the impact of acute muscle wasting on 90-day mortality in older patients with severe pneumonia using ultrasound and chest computed tomography (CT). Quadriceps muscle layer thickness was measured via ultrasound on days 1, 7, and 14, and cross-sectional area of the erector spinae muscle was assessed using chest CT on days 1 and 14 in patients aged ≥ 65years old. The primary outcome was all-cause 90-day mortality. Receiver operating characteristic curves were conducted for muscle loss to predict 90-day mortality. Cox proportional hazard models and Kaplan-Meier survival curves were employed to evaluate the association between muscle loss and 90-day mortality. Sixty-two patients were enrolled with median age of 80.2years, 29 (46.8%) were men and 28 (45.2%) patients died. Muscle mass measured using ultrasound and CT decreased significantly from baseline to day 14 in the non-survivor group. Muscle loss assessed by ultrasound (with minimum and maximum pressure) and CT independently predicted all-cause 90-day mortality (adjusted hazard ratios = 1.497, 1.400 and 1.082; P < 0.001, P = 0.002, and P = 0.004; respectively), and cutoff values of muscle loss were 0.34cm, 0.11cm and 4.92cm2, correspondingly. A higher muscle loss had an increased risk of 90-day mortality. Acute muscle wasting assessed by ultrasound and chest CT persisted for 14days and was an independent predictor of adverse outcomes in older patients with severe pneumonia. A greater decline in muscle mass was associated with a higher 90-day mortality risk.

Inflammation and altered metabolism impede efficacy of functional electrical stimulation in critically ill patients

BackgroundCritically ill patients suffer from acute muscle wasting, which is associated with significant physical functional impairment. We describe data from nested muscle biopsy studies from two trials of functional electrical stimulation (FES) that did not shown improvements in physical function.MethodsPrimary cohort: single-centre randomized controlled trial. Additional healthy volunteer data from patients undergoing elective hip arthroplasty. Validation cohort: Four-centre randomized controlled trial. Intervention: FES cycling for 60-90min/day. Analyses: Skeletal muscle mRNA expression of 223 genes underwent hierarchal clustering for targeted analysis and validation.ResultsPositively enriched pathways between healthy volunteers and ICU participants were “stress response”, “response to stimuli” and “protein metabolism”, in keeping with published data. Positively enriched pathways between admission and day 7 ICU participants were “FOXO-mediated transcription” (admission = 0.48 ± 0.94, day 7 = − 0.47 ± 1.04 mean log2 fold change; P = 0.042), “Fatty acid metabolism” (admission = 0.50 ± 0.67, day 7 = 0.07 ± 1.65 mean log2 fold change; P = 0.042) and “Interleukin-1 processing” (admission = 0.88 ± 0.50, day 7 = 0.97 ± 0.76 mean log2 fold change; P = 0.054). Muscle mRNA expression of UCP3 (P = 0.030) and DGKD (P = 0.040) decreased in both cohorts with no between group differences. Changes in IL-18 were not observed in the validation cohort (P = 0.268). Targeted analyses related to intramuscular mitochondrial substrate oxidation, fatty acid oxidation and intramuscular inflammation showed PPARγ-C1α; (P < 0.001), SLC25A20 (P = 0.017) and UCP3 (P < 0.001) decreased between admission and day 7 in both arms. LPIN-1 (P < 0.001) and SPT1 (P = 0.044) decreased between admission and day 7. IL-18 (P = 0.011) and TNFRSF12A (P = 0.009) increased in both arms between admission and day 7. IL-1β (P = 0.007), its receptor IL-1R1 (P = 0.005) and IL-6R (P = 0.001) decreased in both arms between admission and day 7. No between group differences were seen in any of these (all p > 0.05).ConclusionsIntramuscular inflammation and altered substrate utilization are persistent in skeletal muscle during first week of critical illness and are not improved by the application of Functional Electrical Stimulation-assisted exercise. Future trials of exercise to prevent muscle wasting and physical impairment are unlikely to be successful unless these processes are addressed by other means than exercise alone.

Myostatin/Activin Receptor Ligands in Muscle and the Development Status of Attenuating Drugs.

Muscle wasting disease indications are among the most debilitating and often deadly noncommunicable disease states. As a comorbidity, muscle wasting is associated with different neuromuscular diseases and myopathies, cancer, heart failure, chronic pulmonary and renal diseases, peripheral neuropathies, inflammatory disorders, and, of course, musculoskeletal injuries. Current treatment strategies are relatively ineffective and can at best only limit the rate of muscle degeneration. This includes nutritional supplementation and appetite stimulants as well as immunosuppressants capable of exacerbating muscle loss. Arguably, the most promising treatments in development attempt to disrupt myostatin and activin receptor signaling because these circulating factors are potent inhibitors of muscle growth and regulators of muscle progenitor cell differentiation. Indeed, several studies demonstrated the clinical potential of “inhibiting the inhibitors,” increasing muscle cell protein synthesis, decreasing degradation, enhancing mitochondrial biogenesis, and preserving muscle function. Such changes can prevent muscle wasting in various disease animal models yet many drugs targeting this pathway failed during clinical trials, some from serious treatment-related adverse events and off-target interactions. More often, however, failures resulted from the inability to improve muscle function despite preserving muscle mass. Drugs still in development include antibodies and gene therapeutics, all with different targets and thus, safety, efficacy, and proposed use profiles. Each is unique in design and, if successful, could revolutionize the treatment of both acute and chronic muscle wasting. They could also be used in combination with other developing therapeutics for related muscle pathologies or even metabolic diseases.

The impact of sarcopenia and acute muscle mass loss on long-term outcomes in critically ill patients with intra-abdominal sepsis.

BackgroundSarcopenia is a known risk factor for poor outcomes across many chronic diseases. The impact on outcomes of both pre‐existing sarcopenia and acute muscle wasting (AMW) in acute critical illness caused by sepsis remain unclear.MethodsWe conducted a prospective longitudinal cohort study of critically ill patients with intra‐abdominal sepsis utilizing abdominal computed tomography at sepsis onset to determine baseline skeletal muscle index (SMI). Biomarkers of inflammation and catabolism were measured through 28 days while hospitalized. We performed follow‐up evaluations of strength and physical function at 3, 6, and 12 months, with interval CT analyses at 3 and 12 months to evaluate changes in muscle mass. Measured clinical outcomes included development of chronic critical illness (≥14 days in intensive care with persistent organ dysfunction), long‐term functional status, and 1 year mortality.ResultsAmong 47 sepsis patients enrolled (mean age 53 ± 14 years), half (n = 23; 49%) were sarcopenic at baseline. Overall, sepsis patients exhibited acute and persistent muscle wasting with an average 8% decrease in SMI from baseline at 3 months (P = 0.0008). Sarcopenic (SAR) and non‐sarcopenic (NSAR) groups were similar in regards to age and comorbidity burden. SAR patients had greater acute physiologic derangement (APACHE II, 18 vs. 12.5), higher incidence of multiple organ failure (57% vs. 17%), longer hospital (21 vs. 12 days) and intensive care unit length of stays (13 vs. 4 days), and higher inpatient mortality (17% vs. 0%; all P < 0.05). Pre‐existing SAR was a strong independent predictor of early death or developing chronic critical illness (odds ratio 11.87, 95% confidence interval CI 1.88–74.9; P = 0.009, area under the curve 0.880) and was associated with significantly higher risk of 1‐year mortality (34.9% vs. 4.2%, p = 0.007). Lower baseline SMI was also predictive of poor functional status at 12 months (OR 0.89, 95% confidence interval 0.80–0.99; p = 0.039, area under the curve 0.867). Additionally, SAR patients had AMW with persistent muscle mass loss at 3 months that was associated with decreased health‐related quality of life and SF‐36 physical function domains (P < 0.05). Persistent AMW at 3 months was not predictive of mortality or poor functional status, with return to near‐baseline muscle mass among sepsis survivors by 6 months.ConclusionsCritically ill patients have an acute and persistent loss of muscle mass after intra‐abdominal sepsis, which is associated with decreased health‐related quality of life and physical function at 3 months. However, pre‐existing sarcopenia, rather than persistent acute muscle mass loss at 3 months after sepsis, is independently associated with poor long‐term functional status and increased 1 year mortality.

Pathophysiology and Treatment Strategies of Acute Myopathy and Muscle Wasting after Sepsis.

Sepsis survivors experience a persistent myopathy characterized by skeletal muscle weakness, atrophy, and an inability to repair/regenerate damaged or dysfunctional myofibers. The origins and mechanisms of this persistent sepsis-induced myopathy are likely complex and multifactorial. Nevertheless, the pathobiology is thought to be triggered by the interaction between circulating pathogens and impaired muscle metabolic status. In addition, while in the hospital, septic patients often experience prolonged periods of physical inactivity due to bed rest, which may exacerbate the myopathy. Physical rehabilitation emerges as a potential tool to prevent the decline in physical function in septic patients. Currently, there is no consensus regarding effective rehabilitation strategies for sepsis-induced myopathy. The optimal timing to initiate the rehabilitation intervention currently lacks consensus as well. In this review, we summarize the evidence on the fundamental pathobiological mechanisms of sepsis-induced myopathy and discuss the recent evidence on in-hospital and post-discharge rehabilitation as well as other potential interventions that may prevent physical disability and death of sepsis survivors.

Respiratory Neuropathy as an Important Component of Critical Illness Polyneuromyopathy

ABSTRACT. The attention of neurologists, neurosurgeons, intensive care physicians has been attracted recently by the new PICS (Post Intensive Care Syndrome) symptom complex (PIC) or PIC syndrome — Post Intensive Care Syndrome. One of the most severe options for PIT syndrome is critical illness polymyoneuropathy (CIP). Polyneuropathy (Critical illness polyneuropathies, or CIP) and myopathy (Critical illness myopathies, or CIM) are common complications of critical care. Several syndromes of muscle weakness are combined under the term «Intensive care unit-acquired weakness» or ICUAW. Respiratory neuropathy is a special case of PMCS, where respiratory failure is associated with damage to the neuromuscular apparatus of external respiration. The clinical consequence of respiratory neuropathy is an unsuccessful weaning from ventilator and a long stay of patients in ICU. This systematic review of the literature is an analysis of publications devoted to the main pathogenetic mechanisms of the development of CIP and respiratory neuropathy, diagnostic methods, new therapeutic approaches to the treatment of ICU patients with respiratory neuropathy. The special attention is given to the problem of acute muscle wasting, diagnosis and correction of proteinenergy metabolism disorders in patients with respiratory neuropathy.

Early anthropometry, strength, and function in survivors of critical illness

BackgroundCritically ill patients experience acute muscle wasting and long-term functional impairments, yet this has been inadequately categorised early in recovery. ObjectiveThis observational study aimed to evaluate anthropometry, strength, and muscle function after intensive care unit discharge. MethodsAdult patients able to complete study measures after prolonged intensive care unit stay (≥5 d) were eligible. Demographic and clinical data were collected, and bodyweight, height, triceps skinfold, trunk length, handgrip strength, 6-minute walk test, whole-body dual-energy x-ray absorptiometry, and mid-thigh, knee, and above-ankle circumferences were measured. Body cell mass was calculated from these data. Data are presented as mean (standard deviation) or median [interquartile range]. ResultsFourteen patients (50% male; 57 [10.5] years) were assessed 11.1 (6.9) d after intensive care unit discharge. Patients lost 4.76 (6.66) kg in the intensive care unit. Triceps skinfold thickness (17.00 [8.65] mm) and handgrip strength (12.60 [8.57] kg) were lower than normative data. No patient could commence the 6-minute walk test. Dual-energy x-ray absorptiometry–derived muscle mass correlated with handgrip strength (R = 0.57; 95% confidence interval = 0.06–0.85; p = 0.03), but body cell mass did not. ConclusionsAnthropometry and strength in intensive care unit survivors are below normal. Muscle mass derived from dual-energy x-ray absorptiometry correlates with handgrip strength but body cell mass does not.

Effect of in-bed cycling on acute muscle wasting in critically ill adults: A randomised clinical trial.

To examine whether in-bed cycling assists critically ill adults to reduce acute muscle wasting, improve function and improve quality of life following a period of critical illness. A single-centre, two-group, randomised controlled trial with blinded assessment of the primary outcome was conducted in a tertiary ICU. Critically ill patients expected to be mechanically ventilated for at least 48h were randomised to 30min daily in-bed cycling in addition to usual-care physiotherapy (n=37) or usual-care physiotherapy (n=37). The primary outcome was muscle atrophy of rectus femoris cross-sectional area (RFCSA) measured by ultrasound at Day 10 following study enrolment. Secondary outcomes included manual muscle strength, handgrip strength, ICU mobility score, six-minute walk test distance and health-related quality of life up to six-months following hospital admission. Analysis included the 72 participants (mean age, 56-years; male, 68%) who completed the study. There were no significant between-group differences in muscle atrophy of RFCSA at Day 10 (mean difference 3.4, 95% CI -6.9% to 13.6%; p=.52), or for secondary outcomes (p-values ranged p=.11 to p=.95). In-bed cycling did not reduce muscle wasting in critically ill adults, but this study provides useful effect estimates for large-scale clinical trials. anzctr.org.au Identifier: ACTRN12616000948493.

The Impact of Malnutrition on Acute Muscle Wasting in Frail Older Hospitalized Patients.

Very little is known about the effect of malnutrition on short-term changes of body composition, particularly muscle, among older hospitalized patients. We sought to investigate the association of malnutrition as assessed by the Global Leadership Initiative on Malnutrition (GLIM) criteria with changes of thigh muscle mass and muscle strength among older patients during hospitalization. Forty-one patients (age range 66–97 years, 73% female) participated in this prospective longitudinal observational study. Nutritional status was evaluated using the GLIM criteria on admission and at discharge. Functional status and mid-thigh magnetic resonance imaging (MRI) measurements of cross-sectional area (CSA) were conducted on admission and before discharge. In all, 17% were malnourished and 83% had no malnutrition. Mean mid-thigh muscle CSA declined by 7.0 cm2 (−9%) in malnourished patients during hospitalization (p = 0.008) and remained unchanged among non-malnourished patients (−1%, p = 0.390). Mean mid-thigh CSA of subcutaneous and intermuscular fat did not change significantly during hospitalization in both groups. Malnourished subjects lost 10% of handgrip strength (−1.8 kg) and 12% of knee extension strength (−1.5 kg) during hospitalization. However, the magnitude of both changes did not differ between groups. In a stepwise multiple regression analysis, malnutrition and changes in body weight during hospitalization were the major independent risk factors for the reduction of muscle CSA. Malnutrition according to the GLIM criteria was significantly and independently associated with acute muscle wasting in frail older patients during 2-week hospitalization.

The Role of Bone Secreted Factors in Burn-Induced Muscle Cachexia.

Burn injury results in resorptive bone loss, failure to make new bone, and muscle protein breakdown resulting in cachexia. The purpose of this review is to examine the relationship between bone loss and muscle atrophy in burn injury with a view to understanding the process at work and how it may apply to other conditions that have similar features. We present data suggesting that the use of bisphosphonates in the first 10days following the burn prevents not only the resorptive bone loss but also the muscle wasting. While an extra-osseous effect of bisphosphonates remains possible, existing evidence points to a paracrine effect of bone on maintenance of muscle mass and strength. Proposed paracrine factors produced by bone include prostaglandin E2 and components of the Wnt signaling pathway. TGFβ may be a bone paracrine factor that causes oxidative damage to muscle. In the light of the pattern of evidence, burn patients suffer acute resorptive bone loss and muscle wasting. This is likely due to the effects of inflammatory cytokines and endogenous glucocorticoid production in exacerbating oxidative stress. Early use of bisphosphonates can maintain bone mass leading to a paracrine effect of bone in the maintenance of muscle mass, although one cannot completely discount a direct effect of bisphosphonate on muscle. Because investigators report this relationship in a variety of conditions in addition to burns, physicians should seriously consider the early use of bisphosphonates to maintain bone and muscle mass in a variety of neuromuscular and skeletal diseases.

Hypothalamic activation is essential for endotoxemia-induced acute muscle wasting.

Growing evidence suggests acute skeletal muscle wasting is a key factor affecting nutritional support and prognosis in critical patients. Previously, plenty of studies of muscle wasting focused on the peripheral pathway, little was known about the central role. We tested the hypothesis whether central inflammatory pathway and neuropeptides were involved in the process. In lipopolysaccharide (LPS) treated rats, hypothalamic NF-κB pathway and inflammation were highly activated, which was accompanied with severe muscle wasting. Central inhibition of nuclear factor kappa-B (NF-κB) pathway activation by infusion of an inhibitor (PS1145) can efficiently reduce muscle wasting as well as attenuate hypothalamic neuropeptides alteration. Furthermore, knockdown the expression of anorexigenic neuropeptide proopiomelanocortin (POMC) expression with a lentiviral vector containing shRNA can significantly alleviate LPS-induced muscle wasting, whereas hypothalamic inflammation or NF-κB pathway was barely affected. Taken together, these results suggest activation of hypothalamic POMC is pivotal for acute muscle wasting caused by endotoxemia. Neuropeptide POMC expression may have mediated the contribution of hypothalamic inflammation to peripheral muscle wasting. Pharmaceuticals with the ability of inhibiting hypothalamic NF-κB pathway or POMC activation may have a therapeutic potential for acute muscle wasting and nutritional therapy in septic patients.

Postintensive care syndrome and the role of a follow-up clinic.

Advancements in the care of critically ill patients in the intensive care unit (ICU) setting have increased patients’ chances of surviving even the most serious illnesses. In fact, most studies in this patient population assign mortality as the primary outcome measure. However, as more patients are surviving to ICU discharge, there is now recognition of many long-term consequences of ICU hospitalization that have formerly gone unidentified. Physical deficits, such as reduced pulmonary function after acute respiratory distress syndrome (ARDS) and muscle wasting and weakness after prolonged ICU stays, can be predicted.1 Researchers are also beginning to examine the psychological consequences and neurocognitive impairment that may result and continue for years after ICU discharge.2 This constellation of impairments and complications was termed postintensive care syndrome by the Society of Critical Care Medicine (SCCM) and defined as “new or worsening problems in physical, cognitive, or mental health status arising after a critical illness and persisting beyond acute care hospitalization.”3 SCCM also recently created the Thrive! Task Force with plans to develop and pilot a patient support network for this cause.4

Sustained Elevation of Circulating Growth and Differentiation Factor-15 and a Dynamic Imbalance in Mediators of Muscle Homeostasis Are Associated With the Development of Acute Muscle Wasting Following Cardiac Surgery*

Acute muscle wasting in the critically ill is common and causes significant morbidity. In a novel human model of acute muscle wasting following cardiac surgery, known or potential circulating modulators of muscle mass--insulin-like growth factor-1, myostatin, and growth and differentiation factor-15--were measured over a week. It was hypothesized that patients who developed acute muscle wasting would show distinct patterns of change in these mediators. A prospective longitudinal observational study of high-risk elective cardiac surgical patients identifying, by ultrasound, those developing muscle wasting. Tertiary cardiothoracic referral center: Royal Brompton Hospital, London, UK. Forty-two patients undergoing elective high-risk cardiothoracic surgery. Circulating insulin-like growth factor-1, myostatin, and growth and differentiation factor-15 were assayed preoperatively and over the first week postoperatively. The ability of growth and differentiation factor-15 to cause muscle wasting in vitro was determined in C2C12 myotubes. Of the 42 patients, 23 (55%) developed quadriceps atrophy. There was an acute decrease in insulin-like growth factor-1 and unexpectedly myostatin, known mediators of muscle hypertrophy and atrophy, respectively. By contrast, plasma growth and differentiation factor-15 concentrations increased in all patients. This increase in growth and differentiation factor-15 was sustained at day 7 in those who developed muscle wasting (day 7 compared with baseline, p<0.01), but recovered in the nonwasting group (p>0.05). Insulin-like growth factor-1 did not recover in those who developed muscle wasting (day 7 compared with baseline, p<0.01) but did in the nonwasting group (p>0.05). Finally, we demonstrated that growth and differentiation factor-15 caused atrophy of myotubes in vitro. These data support the hypothesis that acute muscle loss occurs as a result of an imbalance between drivers of muscle atrophy and hypertrophy. Growth and differentiation factor-15 is a potential novel factor associated with muscle atrophy, which may become a therapeutic target in patients with ICU acquired paresis and other forms of acute muscle wasting.

Molecular Determinants of Acute Muscle Wasting in the ICU

Perioperative Anaesthesia Critical CareTrials Group (PACCT)Centre for Translational Inflammation ResearchUniversity of BirminghamBirmingham, UK *See also p. 982. Supported, in part, by Linde REAL fund (grant for a study of muscle dysfunction in COPD). The authors have not disclosed any potential conflicts of interest.

S73 Circulating Regulators of Acute Muscle Wasting in the Critically Ill: GDF-15 a Potential Novel Driver of Acute Muscle Wasting

IntroductionAcute muscle wasting in the critically ill manifesting as intensive care unit acquired paresis (ICUAP) is common, and causes significant morbidity and mortality. The pathological mechanisms underlying ICUAP are poorly...

STAT3 Activation in Skeletal Muscle Links Muscle Wasting and the Acute Phase Response in Cancer Cachexia

BackgroundCachexia, or weight loss despite adequate nutrition, significantly impairs quality of life and response to therapy in cancer patients. In cancer patients, skeletal muscle wasting, weight loss and mortality are all positively associated with increased serum cytokines, particularly Interleukin-6 (IL-6), and the presence of the acute phase response. Acute phase proteins, including fibrinogen and serum amyloid A (SAA) are synthesized by hepatocytes in response to IL-6 as part of the innate immune response. To gain insight into the relationships among these observations, we studied mice with moderate and severe Colon-26 (C26)-carcinoma cachexia.Methodology/Principal FindingsModerate and severe C26 cachexia was associated with high serum IL-6 and IL-6 family cytokines and highly similar patterns of skeletal muscle gene expression. The top canonical pathways up-regulated in both were the complement/coagulation cascade, proteasome, MAPK signaling, and the IL-6 and STAT3 pathways. Cachexia was associated with increased muscle pY705-STAT3 and increased STAT3 localization in myonuclei. STAT3 target genes, including SOCS3 mRNA and acute phase response proteins, were highly induced in cachectic muscle. IL-6 treatment and STAT3 activation both also induced fibrinogen in cultured C2C12 myotubes. Quantitation of muscle versus liver fibrinogen and SAA protein levels indicates that muscle contributes a large fraction of serum acute phase proteins in cancer.Conclusions/SignificanceThese results suggest that the STAT3 transcriptome is a major mechanism for wasting in cancer. Through IL-6/STAT3 activation, skeletal muscle is induced to synthesize acute phase proteins, thus establishing a molecular link between the observations of high IL-6, increased acute phase response proteins and muscle wasting in cancer. These results suggest a mechanism by which STAT3 might causally influence muscle wasting by altering the profile of genes expressed and translated in muscle such that amino acids liberated by increased proteolysis in cachexia are synthesized into acute phase proteins and exported into the blood.

高齢者への合理的薬物投与のためのクレアチニン・クリアランスの予測

It is relevant to measure the 24-hour creatinine clearance (CLcr) for prescribing renally eliminated drugs for geriatric patients, who have diminished renal function. However, the measurement of CLcr requires accurate sampling of 24-hour urine, which is often unreliable in the elderly. Hence, the prediction of CLcr can serve in place of the actual measurement in dosage adjustments. Indeed, predicted CLcr often differs from the measured CLcr. However, it should be emphasized that the renal function of aged patients is poorly assessed by serum creatinine (Scr) alone, while the predicted CLcr based on S, and easily obtainable parameters, such as age and body weight, can more reasonably approximate the renal clearance of the drugs. It should be noted however, in the use of such predicted CLcr, that the discrepancy between the predicted and measured CLcr may not be clinically acceptable in patients with acute renal failure, liver cirrhosis, muscle wasting, and excess fluid retention.

Spanish toxic oil syndrome (1981): Progress in the identification of suspected toxic components in simulated oils.

The Spanish toxic oil syndrome (TOS) caused a unique illness, including acute respiratory effects, eosinophilia, and muscle wasting, in 20 000 people in 1981; epidemiological evidence linked the disease with the consumption of rapeseed oils that had been denatured with aniline. In the study reported here, rapeseed oils were adulterated with aniline and processed to simulate the oils involved in TOS. The aniline-adulterated oils were investigated using radiotracer techniques, advanced sample preparation techniques, including preparative HPLC, and in uitro cell culture toxicity tests. HPLC and GC-MS analysis of the aniline-adulterated oils showed a profile similar to that of «case-related» oils (implicated in TOS), particularly with respect to the anilide contents