phenylephrine-hydrochloride and Muscle-Weakness

Facioscapulohumeral muscular dystrophy (FSHD) has been associated with the genetic and epigenetic molecular features of the CpG-rich D4Z4 repeat tandem array at 4q35. Reduced DNA methylation of D4Z4 repeats is considered part of the FSHD mechanism and has been proposed as a reliable marker in the FSHD diagnostic procedure. We considered the assessment of D4Z4 DNA methylation status conducted on distinct cohorts using different methodologies. On the basis of the reported results we conclude that the percentage of DNA methylation detected at D4Z4 does not correlate with the disease status. Overall, data suggest that in the case of FSHD1, D4Z4 hypomethylation is a consequence of the chromatin structure present in the contracted allele, rather than a proxy of its function. Besides, CpG methylation at D4Z4 DNA is reduced in patients presenting diseases unrelated to muscle progressive wasting, like Bosma Arhinia and Microphthalmia syndrome, a developmental disorder, as well as ICF syndrome. Consistent with these observations, the analysis of epigenetic reprogramming at the D4Z4 locus in human embryonic and induced pluripotent stem cells indicate that other mechanisms, independent from the repeat number, are involved in the control of the epigenetic structure at D4Z4.

Topics: Choanal Atresia; CpG Islands; DNA Methylation; Epigenesis, Genetic; Face; Homeodomain Proteins; Humans; Microphthalmos; Muscle Weakness; Muscular Dystrophy, Facioscapulohumeral; Nose; Primary Immunodeficiency Diseases; Protein Processing, Post-Translational; Tandem Repeat Sequences

A 64-year-old man was referred to our hospital, for a second opinion, with fever, skin lesions and general muscle pain. He has been treated in another hospital with antibiotics on suspicion of erysipelas. A week later skin lesions developed on the metacarpophalangeal and proximal carpophalangeal joints of the hands and nose. His mobility was impaired due to muscle pain and muscle weakness. He also showed proximal muscle atrophy and most importantly a typical heliotrope rash in the eyes. Based on these clinical observations, the most likely diagnosis was dermatomyositis. The diagnosis was confirmed by the presence of increased serum creatine kinase levels and abnormalities in skin and muscle biopsy. Prednisone (70 mg/kg) was initiated, but after 19 days the patient developed a Pneumocystis jiroveci pneumonia. He died of respiratory failure a few days later.

Topics: Dermatomyositis; Exanthema; Fatal Outcome; Hand; Humans; Male; Middle Aged; Muscle Weakness; Muscle, Skeletal; Muscular Atrophy; Myalgia; Nose; Pneumocystis carinii; Pneumonia, Pneumocystis

Inspiratory muscle weakness is a recognised cause of unexplained dyspnoea. It may be suggested by the finding of a low static inspiratory mouth pressure (MIP), but MIP is a difficult test to perform, with a wide normal range; a low MIP may also occur if the patient has not properly performed the manoeuvre. Further investigation conventionally requires balloon catheters to obtain oesophageal (Poes) and transdiaphragmatic pressure (Pdi) during sniffs or phrenic nerve stimulation. Two non-invasive tests of inspiratory muscle strength have recently been described--nasal pressure during a maximal sniff (Sn Pnas) and mouth pressure during magnetic stimulation of the phrenic nerves (Tw Pmo). The use of these two tests in combination might identify patients without inspiratory muscle weakness who are unable to produce a satisfactory MIP< therefore avoiding the need for investigation with balloon catheters.. Thirty consecutive patients with clinically suspected inspiratory muscle weakness and a low MIP underwent both conventional (Sn Poes and Tw Pdi) and non-invasive testing (Sn Pnas and Tw Pmo). Weakness was considered to be excluded by a Sn Poes of > or = 80 cm H20 or a Tw Pdi of > or = 20 cm H20. The limit values used to test the hypothesis were Sn Pnas > or = 70 cm H20 or Tw Pmo > or = 12 cm H20.. Inspiratory muscle weakness was excluded in 17 of the 30 patients. Fifteen of these would have been identified using Sn Pnas and Tw Pmo, with better results when the two tests were combined. The cut off values selected for Sn Pnas and Tw Pmo were shown by ROC plots to indicate normal strength conservatively, avoiding failure to detect mild degrees of weakness. No patient with global weakness was considered normal by Sn Pnas or Tw Pmo.. In most patients with normal inspiratory strength and a low MIP, Tw Pmo and Sn Pnas used in combination can reliably exclude global inspiratory muscle weakness, reducing the number of patients who need testing with balloon catheters.

Topics: Adult; Aged; Diaphragm; Dyspnea; Female; Humans; Magnetics; Male; Middle Aged; Mouth; Muscle Weakness; Nose; Phrenic Nerve; Pressure; Respiration; Respiratory Muscles