Demonstration of reversible priming of human neutrophils using platelet- activating factor

Exposure of neutrophils to agents such as lipopolysaccharide, tumor necrosis factor-alpha (TNF-alpha), and the granulocyte-macrophage colony-stimulating factor causes a major upregulation of subsequent agonist-induced NADPH oxidase activation. This priming effect is a prerequisite for neutrophil-mediated tissue damage and has been widely considered to be an irreversible process. We have investigated the potential for neutrophils to recover from a priming stimulus by studying the effects of platelet-activating factor (PAF). PAF did not stimulate respiratory burst activity directly, but caused a rapid (maximal at 10 minutes) and concentration-dependent (EC50 50.2 nmol/L) increase in N-formyl-methionyl-leucyl-phenylalanine (fMLP)-stimulated superoxide anion release. At time-points > 10 minutes, this priming effect spontaneously declined, with return to basal levels of fMLP- stimulated superoxide anion generation by 120 minutes. An identical priming time-course was observed with N-methyl carbamyl PAF, a nonmetabolizable analogue of PAF, indicating that the transient nature of PAF-induced priming was not secondary to PAF metabolism. Two structurally diverse PAF receptor antagonists (UK-74,505 and WEB 2086), added 10 minutes after PAF addition, increased the rate of decay of the priming effect. In contrast, TNF-alpha-induced priming, which was of a similar magnitude to that observed for PAF, was slower to evolve (maximal at 30 minutes) and remained constant for at least 120 minutes. The reversible nature of PAF-induced priming was confirmed by demonstrating that PAF-, but not TNF-alpha-, induced cell polarization (shape change) and CD11b-dependent neutrophil binding of albumin-coated latex beads was also transient, with return to basal, unstimulated levels by 120 minutes. Furthermore, cells that had spontaneously deprimed following PAF exposure retained their capacity to be fully reprimed by a subsequent addition of either PAF or TNF-alpha. These data imply that neutrophil priming is not an irreversible event: the demonstration of a cycle of complete priming, depriming, and repriming offers the potential for functional recycling of neutrophils at sites of inflammation.     

Biochemical markers of bone turnover in seronegative spondylarthropathy: relationship to disease activity

To investigate bone turnover in patients with seronegative spondylarthropathy, a bone formation marker, type 1 procollagen carboxy- terminal propeptide (P1CP), and resorption markers, the pyridinium cross-links of collagen [urinary free (f) PYR and DPYR], were measured. The median f-PYR, f-DPYR and P1CP (+/-interquartile range) were 15.8 (6.00) nmol/mmol creatinine, 3.8 (2.2) nmol/mmol creatinine and 101.5 (38) micrograms/1, respectively. There was a positive correlation between resorption markers and acute-phase reactants such as C-reactive protein (r = 0.42 for PYR, r = 0.42 for DPYR, P < 0.05), and a negative correlation observed between P1CP and the erythrocyte sedimentation rate (r = -0.64, P < 0.05). In the subgroup of patients with an elevated CRP concentration, the concentration of PYR and DPYR was significantly increased (f-PYR 25.7 vs 15.8 and f-DPYR 6.6 vs 3.8, P < 0.01 for f-PYR, P < 0.05 for f-DPYR). This study suggests than an elevation in acute-phase response in patients with seronegative spondylarthropathy is associated with increased concentration of bone resorption markers with a tendency for reduction in bone formation markers. This may represent uncoupling of bone formation and resorption, leading to bone loss in such patients.      

Postappendectomy fluid collections in children: incidence, nature, and evolution evaluated using US

At the authors' medical center, most patients with postappendectomy fluid collections are treated conservatively. Thirty-two (15%) of 216 children underwent postoperative sonography following appendectomies. In ten patients (31%), a total of 16 fluid collections were found on the initial postoperative sonogram. In the seven patients (70%) whose fluid collections were confined to the pelvis, the condition was treated conservatively and it resolved in 2-9 weeks. In three patients, fluid collections required surgical drainage and proved to be abscesses. In two of the three patients, abscesses were multiple and widely distributed in the abdomen, and the patients were clinically ill. The authors conclude that clinically symptomatic fluid collections develop postoperatively in approximately 5% of children who have undergone appendectomy for acute appendicitis and that the size and course of the fluid collection can be objectively monitored using sonography. Such fluid collections confined to the pelvis ultimately resolve with conservative, nonoperative therapy, although resolution may take up to 2 months.     

Therapeutic implications of thymic uptake of radioiodine in thyroid carcinoma

The management of 38 consecutive patients with differentiated thyroid carcinoma in the period 1991–1996, who each received at least one therapy dose of iodine-131, was reviewed, looking in particular at those in whom anterior mediastinal uptake was demonstrated on scans taken 3 and 7 days post-therapy. Such activity was noted in ten patients. On the basis of clinical follow-up, thyroglobulin measurement and radiological and other scintigraphic imaging, in nine of the ten patients the anterior mediastinal activity was attributed to physiological thymic uptake. Of those nine, all were under 50 years of age; seven were considered disease free, one had residual disease in the neck and one had distant metastases. Physiological uptake by the thymus was more prominent on the 7-day scans and in patients with low tumour volumes. For appropriate patient management it is essential to recognise that physiological uptake of ¹³¹I by the thymus in patients under 50 years of age is a potential cause of false-positive therapy scans. Received 14 November 1997 and in revised form 14 February 1998     

Honorarzahlungspflicht bei Nichterscheinen des Patienten

Ohne Zusammenfassung     

Adult-onset Still''s disease with atypical cutaneous features

INTRODUCTION: The diagnosis of adult-onset Still's disease (AOSD) can be very difficult. There are no specific tests and reliance is usually placed on a symptom complex and the well described typical rash seen in most patients. In recent years, however, other cutaneous manifestations of AOSD have been reported but these are not so well known. OBSERVATIONS: We report a patient with urticaria and fixed plaques and review the other 'atypical' cutaneous findings associated with AOSD. CONCLUSIONS: The diagnosis of AOSD can be made in the absence of the typical Still's rash but in the presence of other atypical cutaneous features.