Polimiosite : investigação clínica em duas irmãs

We present an investigation of a case of polymyositis affecting two sisters of one same parenthood. Their cases have been documented for almost two decades, being investigated by means of a diagnostic protocol which combined clinical findings as well as laboratorial, histopathological and image tests. In both cases, clinical manifestations started in childhood, without signs of involvement of the central and peripheral nervous system. Both patients proved to respond to a therapeutics based on corticosteroids. The degree of relatedness between their parents corroborate the notion that genetic factors may contribute to the development of the disease. ___________________________________________________________________________________________________ RESUMOApresentamos a investigação de dois casos de polimiosite, ocorridos entre irmãs de uma mesma filiação. Seus casos foram documentados ao longo de quase duas décadas, tendo sido diagnosticados utilizando- se de protocolo diagnóstico que combinou achados clínicos, exames laboratoriais, histopatológicos e por imagem. Em ambos os casos, as manifestações clínicas se iniciaram ainda na infância, sendo constatada ausência de acometimento do sistema nervoso central ou periférico. Ambas as pacientes responderam satisfatoriamente a terapia baseada em corticosteróide. O grau de parentesco entre os genitores das pacientes sugere que fatores genéticos podem predispor ao desenvolvimento da doença

A Low Area, Switched-Resistor Based Fractional-N Synthesizer Applied to a MEMS-Based Programmable Oscillator

Abstract-MEMS-based oscillators have recently become a topic of interest as integrated alternatives are sought for quartz-based frequency references. When seeking a programmable solution, a key component of such systems is a low power, low area fractional-N synthesizer, which also provides a convenient path for compensating changes in the MEMS resonant frequency with temperature and process. We present several techniques enabling efficient implementation of this synthesizer, including a switched-resistor loop filter topology that avoids a charge pump and boosts effective resistance to save area, a high gain phase detector that lowers the impact of loop filter noise, and a switched capacitor frequency detector that provides initial frequency acquisition. The entire synthesizer with LC VCO occupies less than 0.36 sq. mm in 0.18 m CMOS. Chip power consumption is 3.7 mA at 3.3 V supply (20 MHz output, no load). Index Terms-MEMS, fractional-N synthesizer, reference frequency, phase-locked loop (PLL), loop filter, high gain phase detector, switched resistor, switched capacitor, frequency acquisition, frequency detection, phase detection, oscillator, temperature stable

Inclusion body myositis: new insights into pathogenesis

Purpose of review: The pathogenesis of sporadic inclusion body myositis is complex and the disease has a relentless course. Recent observations regarding possible mechanisms of disease may provide targets for therapy. Recent findings: Evidence is strengthening that specific T-cell and B-cell responses are ongoing in skeletal muscle in sporadic inclusion body myositis and that cytokines and chemokines generated by an autoimmune response are likely to influence antigen presentation by intramuscular dendritic cells and muscle cells, expression of amyloid precursor protein and the endoplasmic reticulum stress response. Early β-amyloid expression and perhaps aberrant expression of protein processing enzymes, such as E3 ligases, seem to be involved in the myopathic process. NF-κB activation by endoplasmic reticulum stress and cytokine action further stimulates amyloid precursor protein production, exacerbates endoplasmic reticulum stress and increases myostatin content in muscle contributing to muscle atrophy. Summary: Understanding the paradoxes in sporadic inclusion body myositis is important in determining rational therapy for the disease. Amyloid precursor protein is expressed in muscle in other inflammatory muscle diseases but the cellular distribution differs and inclusions do not form so that other metabolic defects seem to be important. Intramuscular immune cells influence muscle function and viability in inclusion body myositis but immunotherapy is ineffective. A useful target for therapy may be restoration of muscle regenerating capacity