Small-airways dysfunction in never smoking asbestos exposed Danish plumbers

Summary Among 701 Copenhagen plumbers we examined the lung function of 23 never smokers, who had removed asbestos insulation and intermittently been exposed to high levels of asbestos for about 25 years without being exposed to welding fume. The plumbers had significantly lower TLC, MEF₂₅, MEF₅₀, closing volume and closing capacity in comparison to 23 never smoking electricians without asbestos exposure. There was no reduction in TL_CO. Pulmonary clearance of aerosolized ^99mTc-DTPA was normal indicating that the asbestos had not induced increases in pulmonary epithelial permeability. However, in 11 of the 23 plumbers the ^99m-Tc-DTPA ventilation scintigrams had a slightly irregular and spotty appearance, which together with the results of the lung function tests are suggestive of small airways' dysfunction. None of the subjects had symptoms or clinical signs of lung disease.     

Calciphylaxis – a topical overview

'Calciphylaxis', a calcification syndrome associated with ischaemic cutaneous necrosis, is acquired naturally in humans in disease states. It is a life and limb-threatening complication, usually observed in patients with renal disease and secondary hyperparathyroidism, but known to occur in the absence of renal or parathyroid disease. The reported mortality rate, which ranges from 60-80%, relates to wound infection, sepsis and organ failure. It is a small-vessel vasculopathy, which is estimated to occur in about 4% of haemodialysis patients. Clinically, violaceous, reticulate areas of cutaneous necrosis and eschar may be evident, particularly in the extremities. In addition to the clinical picture, a raised calcium phosphorous product, an elevated parathyroid hormone level, radiographic evidence of vessel and soft-tissue calcification and the finding of mural calcification affecting small arteries and arterioles on histopathology help to confirm the diagnosis of this entity which generally has a poor prognosis. A high index of suspicion and an active multidisciplinary management approach, with rigorous attention to wound care and prevention of sepsis, are vital in the management of these patients. In this overview, we discuss the pathophysiology, clinical features and associations, risk factors, diagnosis and management issues relating to calciphylaxis.     

Toxicology of FK506 in the cynomolgus monkey: a clinical,biochemical, and histopathological study

We investigated clinical, biochemical, and histopathological parameters in FK506-treated cynomolgus monkeys. Eight monkeys given oral FK506, 1 (n = 4) or 10 (n = 4) mg/kg daily, survived the 90 days of treatment apparently in good health and without significant changes in biochemical and histopathological parameters, as did 2 control monkeys except one monkey on 10 mg/kg/day FK506 orally, who was found to have a malignant lymphoma. In contrast, monkeys given intramuscular FK506 1 mg/kg daily (n = 4) had to be sacrificed at day 20, 25, 32, and 47 because of severe illness. They showed abnormal biochemical parameters (increased serum urea and aspartate aminotransferase activity) and major histopathological changes in the kidney (mesangial cell proliferation and acute tubular necrosis), pancreas (depletion of beta cells), liver (steatosis), and heart (cardiomyopathy). Intramuscular administration of 1 mg/kg daily resulted in serum levels ranging from 10 to 15 ng/ml, while oral administration at a dose of 1 or 10 mg/kg daily resulted in equal or even higher serum levels (range 2–70 ng/ml). Thus, the height of the serum trough level of FK506 using the enzyme immunoassay is not related to the toxicity of FK506 in cynomolgus monkeys.     

Determination of the mean transit time for the transport of aerosolized 99mTc-DTPA across the pulmonary epithelial membrane. A plasma sample method

Summary. During the last decade it has been customary to estimate pulmonary epithelial permeability (P-P) as the pulmonary clearance of inhaled nebulized ^99mTc-DTPA from a time-activity (t-a) curve registered externally by monitoring over the chest. The t-a curve, however, is not defined by the degree of P-P alone but also by factors such as the deposition of the ^99mTc-DTPA in the lungs. To avoid these problems a plasma sample method was derived. It describes P-P by the mean transit time (t?) for the transport of ^99mTc-DTPA across the pulmonary epithelial membrane, t? (L). The calculation of t? (L) involves two steps. Following the inhalation of Tc-DTPA the plasma t-a curve is defined and used to calculate t? for the transport for ^99mTc-DTPA across the pulmonary epithelial membrane, through the E?V and until elimination by the kidneys, t? (L+ECV). Subsequently, ^99mTc-DTPA is injected as a bolus i.v. and the new t-a curve is used to calculate t? for the transport of ^99mTc-DTPA through ECV to the kidneys, t? (ECV). Finally t? (L) is calculated as t? (L) = -t? (L+ECV) t? (ECV). We applied the method in nine non-smoking individuals (median age 25–5 years, range 20–28) and compared the results to t? as calculated from the initial slope of an externally derived t-a curve. The individual t? (L) values were systematically greater than those of the external detection method (P<0·05). It is concluded that the initial slope method overestimates total PCI as measured by the plasma sample method. When choosing between the two methods, special interest should be paid to the inherent problems of the methods.