Widespread pulmonary invasion by malignant pleural mesothelioma: an important diagnostic consideration.

We report a rare case of early and extensive pulmonary invasion of malignant pleural mesothelioma (MPM) in a 70-year-old woman. She first presented with a hydropneumothorax and subsequent workup, including video-assisted thoracoscopy (VAT), confirmed MPM. After VAT, she developed dyspnoea, cough, and widespread pulmonary infiltrates of uncertain aetiology. These infiltrates progressed over the following months, failed to respond to antibiotics, and were strongly fluorodeoxyglucose (FDG)-avid on positron emission tomography (PET). Bronchoalveolar lavage (BAL) yielded extremely viscous fluid containing mesothelioma cells. These cells were also found in the sputum when nebulized deoxyribonuclease (DNase) was trialled to enhance clearance of the pulmonary fluid. The patient deteriorated rapidly with progressive mediastinal and contralateral MPM involvement and died one month later. This case highlights the importance of including tumour invasion as a differential diagnosis of non-resolving pulmonary infiltrates in patients with MPM.

Systemic metabolism in frontotemporal dementia.

OBJECTIVE: To document the metabolic changes in frontotemporal dementia, including serum cholesterol and insulin levels, and compare and contrast these changes to motor neuron disease, where metabolism is proposed to affect disease progression. METHODS: A cohort of 90 patients with dementia (31 behavioral-variant frontotemporal dementia [bvFTD], 30 semantic dementia [SD], and 29 Alzheimer disease [AD]) underwent fasting blood cholesterol, glucose, and peripheral insulin level analysis. Insulin resistance was calculated using the homeostasis model assessment of insulin resistance (HOMA-IR). These results were compared with a cohort of 19 control subjects. RESULTS: The bvFTD cohort had lower high-density lipoprotein (HDL) cholesterol levels compared with control and AD groups, and increased total cholesterol/HDL ratio and triglyceride levels compared with the control group. The SD cohort had increased triglyceride levels compared with control subjects. Both FTD groups had increased fasting insulin levels and HOMA-IR index compared with the control group, and this remained increased in the subjects with bvFTD compared to subjects with AD. CONCLUSION: Both patients with bvFTD and those with SD have increased triglyceride and insulin levels and lower HDL cholesterol levels compared with controls, suggesting a state of peripheral insulin resistance. These factors have been found to affect prognosis in motor neuron disease favorably, although insulin resistance has been proposed as a mechanism promoting neurodegeneration. We discuss the potential role of metabolism in FTD pathophysiology and progression.

Effect of maternal steroid on developing diaphragm integrity.

Antenatal steroids reduce the severity of initial respiratory distress of premature newborn babies but may have an adverse impact on other body organs. The study aimed to examine the effect of maternal steroids on postnatal respiratory muscle function during development and elucidate the mechanisms underlying the potential myopathy in newborn rats. Pregnant rats were treated with intramuscular injections of 0.5 mg/kg betamethasone 7 d and 3 d before birth. Newborn diaphragms were dissected for assessment of contractile function at 2 d, 7 d or 21 d postnatal age (PNA), compared with age-matched controls. The expression of myosin heavy chain (MHC) isoforms and atrophy-related genes and activity of intracellular molecular signalling were measured using quantitative PCR and/or Western blot. With advancing PNA, neonatal MHC gene expression decreased progressively while MHC IIb and IIx isoforms increased. Protein metabolic signalling showed high baseline activity at 2 d PNA, and significantly declined at 7 d and 21 d. Antenatal administration of betamethasone significantly decreased diaphragm force production, fatigue resistance, total fast fibre content and anabolic signalling activity (Akt and 4E-BP1) in 21 d diaphragm. These responses were not observed in 2 d or 7 d postnatal diaphragm. Results demonstrate that maternal betamethasone treatment causes postnatal diaphragmatic dysfunction at 21 d PNA, which is attributed to MHC II protein loss and impairment of the anabolic signalling pathway. Developmental modifications in MHC fibre composition and protein signalling account for the age-specific diaphragm dysfunction.