PPARs and Microbiota in Skeletal Muscle Health and Wasting.

Skeletal muscle is a major metabolic organ that uses mostly glucose and lipids for energy production and has the capacity to remodel itself in response to exercise and fasting. Skeletal muscle wasting occurs in many diseases and during aging. Muscle wasting is often accompanied by chronic low-grade inflammation associated to inter- and intra-muscular fat deposition. During aging, muscle wasting is advanced due to increased movement disorders, as a result of restricted physical exercise, frailty, and the pain associated with arthritis. Muscle atrophy is characterized by increased protein degradation, where the ubiquitin-proteasomal and autophagy-lysosomal pathways, atrogenes, and growth factor signaling all play an important role. Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear receptor family of transcription factors, which are activated by fatty acids and their derivatives. PPARs regulate genes that are involved in development, metabolism, inflammation, and many cellular processes in different organs. PPARs are also expressed in muscle and exert pleiotropic specialized responses upon activation by their ligands. There are three PPAR isotypes, viz., PPARα, -ß/δ, and -γ. The expression of PPARα is high in tissues with effective fatty acid catabolism, including skeletal muscle. PPARß/δ is expressed more ubiquitously and is the predominant isotype in skeletal muscle. It is involved in energy metabolism, mitochondrial biogenesis, and fiber-type switching. The expression of PPARγ is high in adipocytes, but it is also implicated in lipid deposition in muscle and other organs. Collectively, all three PPAR isotypes have a major impact on muscle homeostasis either directly or indirectly. Furthermore, reciprocal interactions have been found between PPARs and the gut microbiota along the gut-muscle axis in both health and disease. Herein, we review functions of PPARs in skeletal muscle and their interaction with the gut microbiota in the context of muscle wasting.

Pneumocystis jirovecii infection of bilateral adrenal glands in an immunocompetent adult: a case report.

Pneumocystis jirovecii (PJ) infection is one of the most common opportunistic infections occurring in patients with HIV/AIDS and other immunocompromised states. It is not known to cause clinically significant illness in immunocompetent hosts. We report a 48-year-old HIV-negative, diabetic male who presented with fever and adrenal insufficiency. Abdominal sonography and PET-CT revealed bilateral enlarged adrenal glands with peripheral enhancement and central necrosis. An endoscopic ultrasound-guided fine-needle aspiration cytology of the left adrenal gland demonstrated well-defined, round cysts of PJ. There was no evidence of pulmonary involvement. The response to first-line treatment was poor and the patient responded to second-line treatment for Pneumocystis infection.

Neurologic Injury After Sacral Neuromodulation.

OBJECTIVE: Neurologic injury after sacral nerve stimulation (SNS) is rare, but the incidence is unknown. Infection is a potential mechanism for neurologic damage. This report illustrates the presentation, pathophysiology, diagnostic considerations, and treatment of epidural infection causing neurologic deficits after SNS. CASE REPORT: We present a case of a woman with severe fecal incontinence due to Crohn's disease who underwent SNS implantation and subsequently developed a wound infection requiring complete device explantation. A few days later, she presented with leg pain and weakness. Urgent evaluation and treatment of epidural infection were performed. She had persistent neurologic deficits 6 months later. CONCLUSIONS: Neurologic sequelae from an infection after SNS are a rare event and should be considered in patients with fevers, leg pain, and neurologic deficits.

Neurobrucellosis in a 9-year-old girl.

Brucellosis is a zoonotic multi-organ infectious disease most frequent in developing countries. Neurobrucellosis a quite rare but serious complication of brucellosis in the pediatric age group manifests with different neurological symptoms and signs. In the present case a 9-year-old girl was referred to our centre with a 9-months history of headache and back pain, facial nerve palsy and right upper limb weakness. She had undergone ventriculoperitoneal shunting surgery due to communicating hydrocephalus. Magnetic resonance imaging revealed a spinal extramedullary intradural mass, two epidural collections in the cervical spine and thickening/abnormal enhancement in the basal cisterns with invasion to medulla and pons. The patient's serum and cerebrospinal serologic tests were found positive for brucellosis. The patient was successfully treated by anti-brucella antibiotic therapy.

Cervical facet joint septic arthritis: a real pain in the neck.

A 64-year-old man with a complex medical history and previous cervical arthritis with discectomy presents with a 2-day history of neck and lower back pain and shortness of breath, associated with left-sided muscle weakness. He has a fever with severe sepsis causing acute renal failure. MRI spine shows evidence of left cervical facet joint septic arthritis at C6-T1. He required 6 weeks of intravenous antibiotics and intensive support with ventilation and haemofiltration. After completion of antibiotics, he made a full recovery and regained neurological function before discharge.

[Infant botulism ­ why honey should be avoided for children up to one year]. / Spädbarnsbotulism ­ skäl att inte ge honung till barn under ett år.

Infant botulism - why honey should be avoided for children up to one year Infant botulism means that Clostridium botulinum colonize and produce toxin in the infant gut, usually during the first year of life. Illness severity varies widely and the incidence may be under-estimated. Infant botulism should be considered in cases of acute muscle weakness or floppiness in infants, especially when accompanied by constipation or feeding difficulties. Respiratory failure and need for mechanical ventilation is common, but full recovery is gradually obtained. Diagnosis is based on stool culture and toxin detection in stool. Botulinum spores are frequently present in honey, which should consequently be avoided for infants.

A Klebsiella pneumoniae liver abscess presenting with myasthenia and tea-colored urine: A case report and review of 77 cases of bacterial rhabdomyolysis.

RATIONALE: Rhabdomyolysis is a well-known syndrome in clinical practice, although rhabdomyolysis caused by a liver abscess is rarely reported and the patient may lack symptoms that are associated with a primary site of infection. Early recognition of this possibility is needed to avoid diagnostic delay and facilitate treatment. We report the case of a 71-year-old woman with a Klebsiella pneumoniae (KP) pyogenic liver abscess who presented with myasthenia and tea-colored urine and also review the 77 reported cases of bacterial rhabdomyolysis. PATIENT CONCERNS: The patient was 71 years old and presenting with a 7-day history of myasthenia and a 3-day history of tea-colored urine, but without fever or abdominal pain. DIAGNOSES: Laboratory testing in our case revealed rhabdomyolysis, and blood culture revealed KP. Abdominal ultrasonography revealed a hypoechoic enclosed mass, and computed tomography (CT) revealed an enclosed low-density mass (8.3 × 6.6 × 6.1 cm). The main diagnoses were a pyogenic liver abscess with rhabdomyolysis. INTERVENTIONS: Empirically intravenous piperacillin-sulbactam and intravenous potassium treatment, as well as fluid infusions and other supportive treatments were provided after admission. After the diagnosis was confirmed and susceptibility test results were available, we adjusted the antibiotics to cefoperazone and sulbactam, which were maintained for 6 weeks. OUTCOMES: The patient's symptoms relieved and the abnormal laboratory parameters corrected. Follow-up abdominal ultrasonography at 24 months after her discharge revealed that the abscess had disappeared. LESSONS: Early recognition and careful consideration of the underlying cause of rhabdomyolysis are critical to improving the patient's prognosis. Thus, physicians should carefully consider the underlying cause in elderly patients who present with rhabdomyolysis, as they may lack symptoms of a primary infection.

Systemic symptoms predict presence or development of severe sepsis and septic shock.

BACKGROUND: Severe sepsis is a major cause of mortality and morbidity globally. As the time to adequate treatment is directly linked to outcome, early recognition is of critical importance. Early, accessible markers for severe sepsis are desirable. The systemic inflammatory response in sepsis leads to changes in vital signs and biomarkers and to symptoms unrelated to the focus of infection. This study investigated whether the occurrence of any of six systemic symptoms could predict severe sepsis in a cohort of patients admitted to hospital for suspected bacterial infections. METHODS: A retrospective, consecutive study was conducted. All adult patients admitted during 1 month to a 550-bed secondary care hospital in western Sweden and given intravenous antibiotics for suspected community-acquired infection were included (n = 289). Symptoms (fever/chills, muscle weakness, localised pain, dyspnea, altered mental status and gastrointestinal symptoms) were registered along with age, sex, vital signs and laboratory values. Patients who fulfilled criteria of severe sepsis within 48 h were compared with patients who did not. Odds ratios for severe sepsis were calculated, adjusted for age, sex and comorbidities. RESULTS: Criteria for severe sepsis were fulfilled by 90/289 patients (31.1%). Altered mental status (OR = 4.29, 95% CI = 2.03-9.08), dyspnea (OR = 2.92, 95% CI = 1.69-5.02), gastrointestinal symptoms (OR = 2.31, 95% CI = 1.14-4.69) and muscle weakness (OR = 2.24, 95% CI = 1.06-4.75) were more common in patients who had or later developed severe sepsis. CONCLUSIONS: Systemic symptoms in combination with other signs of infection should be considered warning signs of severe sepsis.

Neutral sphingomyelinase 2 is required for cytokine-induced skeletal muscle calpain activation.

Calpain contributes to infection-induced diaphragm dysfunction but the upstream mechanism(s) responsible for calpain activation are poorly understood. It is known, however, that cytokines activate neutral sphingomyelinase (nSMase) and nSMase has downstream effects with the potential to increase calpain activity. We tested the hypothesis that infection-induced skeletal muscle calpain activation is a consequence of nSMase activation. We administered cytomix (20 ng/ml TNF-α, 50 U/ml IL-1ß, 100 U/ml IFN-γ, 10 µg/ml LPS) to C2C12 muscle cells to simulate the effects of infection in vitro and studied mice undergoing cecal ligation puncture (CLP) as an in vivo model of infection. In cell studies, we assessed sphingomyelinase activity, subcellular calcium levels, and calpain activity and determined the effects of inhibiting sphingomyelinase using chemical (GW4869) and genetic (siRNA to nSMase2 and nSMase3) techniques. We assessed diaphragm force and calpain activity and utilized GW4869 to inhibit sphingomyelinase in mice. Cytomix increased cytosolic and mitochondrial calcium levels in C2C12 cells (P < 0.001); addition of GW4869 blocked these increases (P < 0.001). Cytomix also activated calpain, increasing calpain activity (P < 0.02), and the calpain-mediated cleavage of procaspase 12 (P < 0.001). Procaspase 12 cleavage was attenuated by either GW4869 (P < 0.001), BAPTA-AM (P < 0.001), or siRNA to nSMase2 (P < 0.001) but was unaffected by siRNA to nSMase3. GW4869 prevented CLP-induced diaphragm calpain activation and diaphragm weakness in mice. These data suggest that nSMase2 activation is required for the development of infection-induced diaphragm calpain activation and muscle weakness. As a consequence, therapies that inhibit nSMase2 in patients may prevent infection-induced skeletal muscle dysfunction.

A 59-year-old man with acute onset of paralysis.

Botulism is a neuroparalytic illness resulting from the action of a potent toxin produced by the organism Clostridium botulinum. It can present with a classic triad of clear mentation, bulbar palsy and symmetric descending paralysis. Treatment is symptomatic and includes a botulinum antitoxin.

Infective endocarditis initially presenting with a dermatomyositis-like syndrome.

Infective endocarditis (IE) may present with rheumatological manifestations such as myalgias, arthralgias, arthritis and back pain. However, muscle inflammation is rare. We present a case of a 68-year-old Hispanic man who presented with 1-month history of tiredness, weight loss, fever, myalgias, muscle weakness and dysphagia to solid food. On physical examination he had severe weakness in the proximal upper and lower extremities, and erythematous eruption involving the upper eyelids, neck and metacarpophalangeal joints. Creatine kinase levels were markedly elevated at 15 809 U/L. MRI of the right thigh revealed intermuscular and intramuscular oedema. Muscle biopsy showed acute necrotising suppurative perimyositis. Blood cultures were positive for methicillin-resistant Staphylococcus aureus. A transoesophageal echocardiogram revealed vegetations in the pulmonic valve. All clinical manifestations were resolved completely with broad-spectrum antibiotics. This case suggests that IE should be considered in the differential diagnosis of a patient presenting with inflammatory myopathy.

Infant botulism following honey ingestion.

An apparently well baby girl born at term was presented with signs and symptoms suggestive of acute onset of generalised floppiness at the age of 3 months. Clinically, the baby had lower motor neuron type of muscle weakness; detailed investigation lead to the diagnosis of neuromuscular junction disorder secondary to botulism toxicity. Further tests confirmed the botulism toxicity secondary to honey ingestion. The baby was treated with specific anticlostridium antibodies; she recovered remarkably, now growing and developing normally.

Ultrasonographic analysis of the neck flexor muscles in patients with chronic neck pain and changes after cervical spine mobilization.

OBJECTIVE: The purpose of this study was to analyze changes in the recruitment of the muscles longus colli (Lco) and sternocledomastoid (SCM) as measured by ultrasonography in patients with chronic neck pain before and immediately after a single cervical Maitland's posterior-anterior central mobilization technique. METHODS: This was a cross-sectional, case-control research design study. Ultrasonographic images of Lco and SCM were taken in 31 patients with chronic neck pain and matched controls during the 5 phases of the craniocervical flexion test before and after a Maitland's posterior-anterior central mobilization session at the cervical spine. Changes in muscle thickness during the test were calculated to infer muscle recruitment. Separate analysis of variance models for each muscle was built. RESULTS: Both groups showed increases in Lco and SCM recruitment between phases (F = 7.95, P < .001; F = 21.29, P < .001), with patients with chronic neck pain demonstrating lesser increases for Lco changes in thickness compared with controls, mainly at phase 5 (-0.09, P = .004; 95% confidence interval [CI], 0.03-0.15). After the mobilization, Lco recruitment increased more significantly in patients with chronic neck pain, and previous difference between groups in phase 5 was no longer significant (-0.07, P = .07; 95% CI, -0.14 to 0.01). The SCM recruitment decreased in phase 1 for patients with chronic neck pain (P = .01; 95% CI, -0.06 to -0.01). CONCLUSION: Cervical mobilization appeared to modulate neck muscles function by increasing deep muscle and reducing superficial muscles recruitment.

Clinical features of cervical pyogenic spondylitis and intraspinal abscess.

STUDY DESIGN: Retrospective study. OBJECTIVES: The purpose of the present study was to elucidate the clinical features of cervical pyogenic spondylitis and intraspinal abscess and to use this knowledge for early diagnosis and treatment. SUMMARY OF BACKGROUND DATA: Cervical pyogenic spondylitis and intraspinal abscess are relatively rare diseases in which accurate diagnosis is difficult at early stage. However, because both diseases can cause severe paralysis and vital crisis at advanced stages, early diagnosis and treatment are very important. METHODS: Fourteen patients (men: 9, women: 5; average age at treatment: 65.4 y; age range: 49-89 y) with cervical pyogenic spondylitis and/or intraspinal abscess were treated in our hospital. We analyzed their initial symptoms, initial diagnosis, duration between the appearance of initial symptoms and final diagnosis, symptoms at final diagnosis, level of the affected cervical spine, predisposing factors, organisms, and treatments. RESULTS: Initial symptoms included neck pain with fever (n=7), neck pain without fever (n=3), pharyngeal pain with fever (n=1), muscle weakness in both the upper and lower extremities (n=1), gait disturbance (n=1), and numbness of the lower extremities (n=1). Patients were initially diagnosed with meningitis (n=4), fever of unknown origin (n=2), cervical spondylosis (n=2), polymyalgia rheumatica (n=1), upper respiratory tract inflammation (n=1), metastatic spinal tumor (n=1), cervical spondylotic myelopathy (n=1), and cervical disc herniation (n=1). Of the 14 patients, 1 was correctly diagnosed with cervical pyogenic spondylitis. CONCLUSIONS: The initial symptoms of cervical pyogenic spondylitis and intraspinal abscess varied and neck pain with fever was not essential. Therefore, doctors should consider the possibility of cervical pyogenic spondylitis and repeat the assessments of the clinical examination for early diagnosis of this disease.

[Infant botulism in France, 1991-2009]. / Le botulisme infantile en France, 1991-2009.

Infant botulism is caused by the ingestion of spores of Clostridium botulinum and affects newborns and infants under 12 months of age. Ingested spores multiply and produce botulinum toxin in the digestive tract, which then induces clinical symptoms. A single French case was described in the literature prior to 1991. We describe the cases of infant botulism identified in France between 1991 and 2009. All clinical suspicions of botulism must be declared in France. Biological confirmation of the disease is provided by the National reference laboratory for anaerobic bacteria and botulism at the Pasteur Institute. During this period, 7 cases of infant botulism were identified, 1 per year from 2004 to 2008 and 2 in 2009. The median age of affected infants was 119 days and all were female. All infants presented with constipation and oculomotor symptoms. All were hospitalized and required mechanical ventilation. The infants recovered from their botulism. The diagnosis of infant botulism was biologically confirmed for all patients. One 4-month-old infant was treated with a single dose of the human-derived botulism antitoxin specific for infant botulism types A and B (BabyBIG®). The infants all had different feeding habits ranging from exclusive breast feeding to a mix of formula feeding and solid food consumption. The consumption of honey, the only documented risk food for this disease, was reported for 3 of the infants. The honey had been placed on the pacifier of 2 infants and directly in the mouth of the 3rd by the mother. Infant botulism, a form of botulism that was previously rarely recognized in France, has been reported more frequently during the last 6 years. This disease remains rare but nonetheless severe. In light of recent epidemiological data, efforts to raise awareness among parents of infants and health professionals on the danger of infant botulism and particularly, its association with honey consumption seems necessary.