ECG abnormalities in polymyositis.

Electrocardiographic abnormalities were found in 25 (32.5%) of 77 patients with polymyositis. Left anterior hemiblock (13.0%) and right bundle-branch block (9.1%) were the most common abnormalities. No association could be found between these defects and clinical activity of polymyositis, severity of duration of disease, or degree of creatine kinase level elevation. Similarly, there was no association with age or the presence of certain clinical conditions such as rash or arthritis. In only two patients, both children, did an ECG abnormality improve with corticosteroid therapy. Three patients with heart block died suddenly. This study points up the need for continual close observation of patients with inflammatory muscle disease, even after apparent remission.

Depletion of serum hemopexin in fulminant rhabdomyolysis. Evidence for an interaction of hemopexin with myoglobin-derived heme.

Hemopexin is a normal serum glycoprotein that functions as a carrier for intravascularly liberated free heme. Although its role is well established in the reutilization of hemoglobin-derived heme, there have been no previous clinical data to support its suspected interaction with heme released in the degradation of myoglobin. In a patient with fulminant rhabdomyolysis, we found depletion of serum hemopexin in the presence of high serum levels of myoglobin with normal levels of haptoglobin and hemoglobin. This combination of laboratory findings is evidence for an interaction between myoglobin-derived heme and hemopexin and implies a role for hemopexin in the catabolism of myoglobin. These findings support the proposed induction mechanism for observed increases of serum hemopexin in Duchenne muscular dystrophy and in polymyositis.

Serum myoglobin in myocardial infarction: the "staccato phenomenon." Is acute myocardial infarction in man an intermittent event?

When serum was sampled frequently and soon after acute myocardial infarction, myoglobinemia was extremely common, occurring in 12 of 13 selected patients. Myoglobin first appeared in the serum within a few hours after infarction, but not consistently earlier than creatine phosphokinase. The peak level of serum myoglobin was reached appreciably earlier than the peak values of serum creatine phosphokinase activity. Time of earliest myoglobin appearance in the serum, peak level of myoglobin measured, and duration of detectable myoglobin release all correlated poorly with clinical and biochemical estimates of severity of myocardial infarction. There was no correlation between myoglobin levels and infarct size as estimated from creatine phosphokinase kinetics. Myoglobin appeared in the serum in multiple short "staccato" bursts, or episodes, often lasting only one to two hours. The hypothesis is suggested that the pattern of myoglobin appearance is a reflection of the episodic nature of acute myocardial infarction. Although isolated myoglobin determination may not be useful at present, for quantification of total myocardial damage, its pattern of release may be a sensitive marker for studying the time course of infarction, and may be useful to evaluate therapeutic interventions designed to interrupt an ongoing syndrome of myocardial necrosis.

Serologic evidence for acute toxoplasmosis in polymyositis-dermatomyositis. Increased frequency of specific anti-toxoplasma IgM antibodies.

Several case reports have suggested an association between acquired toxoplasmosis and polymyositis-dermatomyositis. Because the presence of anti-Toxoplasma IgM antibodies suggests recent infection, 58 patients with polymyositis-dermatomyositis (from two medical centers) were examined for the presence of IgM antibodies using a specific indirect immunofluorescent technique. Serum samples were also examined for antibodies using the Sabin-Feldman dye test and complement fixation methods. Of 58 patients with polymyositis-dermatomyositis, 29 (50 percent) had positive Sabin-Feldman dye test results and 14 (24 percent) had positive IgM immunofluorescent findings. This is higher than the expected frequency. None of the patients with negative Sabin-Feldman dye test results had IgM immunofluorescent antibodies. Furthermore, IgM immunofluorescent antibodies were associated with the presence and titer of both Sabin-Feldman dye test and complement fixation antibodies. Evidence that the presence of antinuclear antibody and rheumatoid factor did not influence these results is presented. Patients with muscular dystrophy and systemic lupus erythematosus (with or without myositis) did not have an increased frequency of anti-Toxoplasma IgM immunofluorescent antibodies.

Elevated levels of cerebrospinal fluid guanosine 3',5'-cyclic monophosphate (C-GMP) in systemic lupus erythematosus.

Cerebrospinal fluid samples from patients with systemic lupus erythematosus (SLE) and neurologic involvement were evaluated for guanosine 3',5'-cyclic monophosphate (C-GMP) and cyclic adenosine monophosphate (C-GMP) content by radioimmunoassay and radioassay, respectively. Twenty-five samples from 15 patients with SLE had an average C-GMP level of 2.4 nM +/- 0.44 (average +/- SE) compared with 0.68 nM +/- 0.14 in a control group with lumbosacral pain (p less than 0.0002). No significant difference was noted in C-AMP content between patients with SLE and control subjects. C-GMP levels in cerebrospinal fluid samples from patients with SLE who had changing neurologic disease were higher than in those with stable neurologic disease. Elevated C-GMP levels in cerebrospinal fluid correlated with the leukocyte number in cerebrospinal fluid (r = 0.53 p less than 0.01), but not with the initial pressure, protein concentration or daily prednisone dosage. Experimental results suggested that leukocytes in the cerebrospinal fluid were not the source of elevated C-GMP levels. Thus, elevated C-GMP levels in cerebrospinal fluid of patients with SLE appeared to reflect neurologic involvement. C-GMP levels were alos found to be elevated in five patients with other active neurologic diseases; thus, measurement of C-GMP in cerebrospinal fluid may have more general diagnostic value.

Myoglobinemia following acute myocardial infarction.

Myoglobin was identified in the serum of 11 of 21 patients after myocardial infarction by a sensitive specific complement fixation technic. This method allowed detection of as little as 0.03 mug of myoglobin. The assay tended to underestimate small concentrations of myoglobin due to serum interference. Myoglobinuria occurred with myoglobinemia but did not reflect the level of myoglobinemia or the duration of elevated serum levels. Larger amounts of myoglobin, 0.4 mug/ml or greater, were found in patients with severe infarctions, three of four of whom died as a result of this illness.

Growth regulator from spinal cord: produced in cultures of glial cells.

Spinal cord cultures produced a regulatory factor which inhibited myogenesis. After serial passage (x 3) production of this factor continued as neuronal cells disappeared and large, pale polygonal cells rich in cytoplasmic microfilaments with morphology of astrocyte precursors became predominant. These glial cells responded to dibutyryl cyclic AMP by assuming a star-shaped appearance with multiple, radiating cytoplasmic processes. Cultures active in production of the growth regulator also produced nonneuronal-type enolase and glutamine synthetase. It is suggested that the growth regulator is produced by astrocytic glia in culture.

Possible role for tumour necrosis factor inhibitors in the treatment of resistant dermatomyositis and polymyositis: a retrospective study of eight patients.

OBJECTIVE: To understand the use of tumour necrosis factor (TNF)alpha inhibitors in refractory dermatomyositis and polymyositis in an academic centre. METHODS: A retrospective study of eight patients with dermatomyositis or polymyositis refractory to corticosteroids and immunosuppressives who were treated with TNF inhibitors between 1998 and 2004. RESULTS: 8 patients with dermatomyositis or polymyositis who were treated with TNF inhibitors as adjunct treatment were identified. The mean (SD) duration of disease before initiation of TNF inhibitors was 8.5 (4.4) years. The patients failed to respond to treatment with corticosteroids (oral and intravenous); intravenous immunoglobulin and immunosuppressants (methotrexate, azathioprine, mycophenolate mofetil and leflunomide); 4.5 (1.4) immunosuppressants had been used before TNF treatment. Six patients were treated with etanercept alone, one with infliximab and one sequentially with both agents. Of the eight patients, six showed a favourable response with improved motor strength and decreased fatigue after 15.2 (6.5) months. Two of the patients did not respond after 4 (1.4) months and TNF inhibitors were discontinued. Responders showed a 54.4% (27.7%) decrease in serum concentration of creatine kinase, which was grossly abnormal (4463.5 (4036.4) U/l). Non-responders had similar reductions in creatine kinase concentration (56.1% (20.4%)), but their pre-treatment concentrations were in the normal range (118.5 (19.1) U/l). CONCLUSION: Anti-TNF agents may be useful in some patients with refractory dermatomyositis or polymyositis.

Interlaboratory comparison of red-cell ATP, 2,3-diphosphoglycerate and haemolysis measurements.

BACKGROUND AND OBJECTIVES: Red blood cell (RBC) storage systems are licensed based on their ability to prevent haemolysis and maintain RBC 24-h in vivo recovery. Preclinical testing includes measurement of RBC ATP as a surrogate for recovery, 2,3-diphosphoglycerate (DPG) as a surrogate for oxygen affinity, and free haemoglobin, which is indicative of red cell lysis. The reproducibility of RBC ATP, DPG and haemolysis measurements between centres was investigated. MATERIALS AND METHODS: Five, 4-day-old leucoreduced AS-1 RBC units were pooled, aliquotted and shipped on ice to 14 laboratories in the USA and European Union (EU). Each laboratory was to sample the bag twice on day 7 and measure RBC ATP, DPG, haemoglobin and haemolysis levels in triplicate on each sample. The variability of results was assessed by using coefficients of variation (CV) and analysis of variance. RESULTS: Measurements were highly reproducible at the individual sites. Between sites, the CV was 16% for ATP, 35% for DPG, 2% for total haemoglobin and 54% for haemolysis. For ATP and total haemoglobin, 94 and 80% of the variance in measurements was contributed by differences between sites, and more than 80% of the variance for DPG and haemolysis measurements came from markedly discordant results from three sites and one site, respectively. In descending order, mathematical errors, unvalidated analytical methods, a lack of shared standards and fluid handling errors contributed to the variability in measurements from different sites. CONCLUSIONS: While the methods used by laboratories engaged in RBC storage system clinical trials demonstrated good precision, differences in results between laboratories may hinder comparative analysis. Efforts to improve performance should focus on developing robust methods, especially for measuring RBC ATP.