Exercise with stepwise increasing work loads until exhaustion leads to a curvilinear increase of lactate in blood and typical lactate kinetics in the post-exercise period. Lactate kinetics in blood during exercise and recovery results from diffusion along gradients between muscle and blood and simultaneous elimination. Therefore, a general diffusion-elimination model is presented from which maximal rate of elimination (Em), individual anaerobic threshold (IAT), gradient between muscle and blood (deltaC-deltaCEm), muscle volume working above the IAT (Vm), individual membrane constant (Mc), quantity of lactate accounting for lactate gradient (Agrad), and whole body lactate (Anet) can be obtained. For demonstration purpose, this model was applied to a highly trained athlete. In this example, all constants and variables mentioned above as well as an equation reflecting individual lactate kinetics were calculated. Furthermore, the IAT was determined in 61 athletes participating in different events. In general, it can be demonstrated that with increasing aerobic capacity the lactate concentration at the IAT decreases. The lactate concentration at the IAT varies interindividually within broad limits, thus emphasizing the need for individual assessment.

To elucidate whether the fraction of CD28(-) T cells within the CD4(+) T-cell population is a major source of Th1-like and proinflammatory cytokine production driving Wegener's granulomatosis (WG) granuloma formation, we analyzed the phenotype and functional characteristics of peripheral blood CD4(+)CD28(-) T cells and of T cells in granulomatous lesions of 12 patients with active WG. Surface markers and intracytoplasmic cytokine and perforin expression were assessed by flow cytometry. Cytokine secretion was measured by enzyme-linked immunosorbent assay. Immunohistological studies demonstrated interferon-gamma and tumor necrosis factor-alpha cytokine positivity attributable to CD4(+)CD28(-) T cells in granulomatous lesions. Peripheral blood CD4(+)CD28(-) T cells expressed CD57, also found on natural killer cells, and intracytoplasmic perforin. They were generally CD25 (interleukin-2 receptor)-negative. CD18 (adhesion molecule beta(2)-integrin) was strongly up-regulated on CD4(+)CD28(-) T cells, whereas only a minority of CD4(+)CD28(+) T cells expressed CD18. CD4(+)CD28(-) T cells appeared as a major source of interferon-gamma and tumor necrosis factor-alpha. In contrast, CD4(+)CD28(+) T cells were able to produce and secrete a wider variety of cytokines including interleukin-2. One-quarter of CD4(+)CD28(+) T cells expressed the activation marker CD25, but they lacked perforin. Thus, CD4(+)CD28(-) T cells appeared more differentiated than CD4(+)CD28(+) T cells. They displayed Th1-like cytokine production and features suggestive of the capability of CD4(+) T-cell-mediated cytotoxicity. CD4(+)CD28(-) T cells may be recruited into granulomatous lesions from the blood via CD18 interaction, and may subsequently promote monocyte accumulation and granuloma formation through their cytokine secretion in WG.

No abstract

Seventeen male physical education students performed three types of treadmill exercise: (1) progressive exercise to exhaustion, (2) prolonged exercise of 50 min duration at the anaerobic threshold of 4 mmol . l-1 blood lactate (AE), (3) a single bout of short-term high-intensity exercise at 156% of maximal exercise capacity in the progressive test, leading to exhaustion within 1.5 min (ANE). Immediately before and after ANE and before, during, and after AE adrenaline, noradrenaline, growth hormone, cortisol, insulin, testosterone, and oestradiol were determined in venous blood, and glucose and lactate were determined in arterialized blood from the earlobe. Adrenaline and noradrenaline increased 15 fold during ANE and 3--4 fold and 6--9 fold respectively during AE. The adrenaline/noradrenaline ratio was 1 : 3 during ANE and 1 : 10 during AE. Cortisol increased by 35% in ANE (12% of which appeared in the postexercise period) and 54% in AE. Insulin increased during ANE but decreased during AE. Testosterone and oestradiol increased by 14% and 16% during ANE and by 22% and 28% during AE. The results point to a markedly higher emotional stress and higher sympatho-adrenal activity in anaerobic exercise. Growth hormone and cortisol appear to be the more affected by intense prolonged exercise. Taking plasma volume changes and changes of metabolic clearance rates into consideration, neither of the exercise tests appeared to affect secretion of testosterone and oestradiol.

Objective. To assess the effectiveness of pulse cyclophosphamide (CYC) in the treatment of Wegener's granulomatosis (WG) and to identify the patients who are responsive to the treatment.Methods. The prospective study included 43 patients with biopsy-proven WG. Clinical, radiographic, laboratory, and immunologic data were evaluated for predicitive values regarding the outcome of pulse CYC therapy.Results. Only 42% of the patients showed complete or partial remission that lasted at least 6 months after cessation of pulse CYC therapy. These responders had a higher frequency of disease activity limited to the upper and lower respiratory tract (39%, versus 8% in the nonresponder group; P < 0.05) and had lower titers of classic antineutrophil cytoplasmic antibody (cANCA) prior to treatment (<1:64 42%, versus 6% in the nonresponder group; P < 0.05). In the 58% of patients who did not respond to pulse CYC treatment, there was both systemic disease involving more than 4 organ systems (mainly, the heart, nervous system, eye, and

The absence of cANCA, anti-PR3, and anti-MPO shows that with appropriate assay conditions, ANCA testing assists in the differentiation between SLE and the ANCA-associated vasculitides. The lack of a correlation between pANCA or any ANCA subspecificity and clinical manifestations suggests that ANCA do not identify particular clinical subsets among SLE patients, including those with lupus vasculitis.

A prospective study correlating high-resolution computed tomography (HRCT), lung function tests (PFT) and bronchoalveolar lavage (BAL) cytology in patients with interstitial lung disease (ILD) associated with rheumatoid arthritis (RA). Fifty-three RA patients with suspected ILD (19 men, 34 women) underwent 71 HRCT (14 of 53 with sequential HRCT, mean follow-up 24.3 months). The HRCT evaluation by two observers on consensus included a semi-quantitative characterisation of lesion pattern and profusion on representative anatomical levels. Fifty-two HRCT were followed by PFT and BAL. Agreement or discordance of HRCT-, PFT- and BAL findings were analysed with Pearson's correlation, kappa score and McNemar's test. Tobacco-fume exposure was estimated in pack years. Smoking/non-smoking groups were compared with Student's t test. In 49 of 53 patients, HRCT was suggestive of ILD associated with RA (66 of 71 HRCT). Reticular lesions were found in 40 of 53 patients, in 15 of 40 presenting as mixed pattern with ground-glass opacities (GGO). Pure reticular patterns predominated in patients with long duration of ILD (p>0.01). Pure GGO were not observed. Lesion profusion was highly variable and correlated moderately negative with diffusion capacity (mean 88.2% (SD +/- 20.9%); r=-0.54; p<0.001) and very weak with vital capacity and FEV1 (mean values 92.2% (SD +/- 18.3%); r=-0.27; p<0.05 and 89.8% (SD +/- 17.5%); r=-0.31; p<0.01). In patients with GGO, BAL differentials tended towards neutrophilia (kappa=0.39; p=0.04; McNemar test p>0.2), but not towards lymphocytosis (kappa=0.10; p=0.23; McNemar test p>0.2). Differences in smoking history were not significant (p>0.1). The HRCT appears most appropriate for the detection and follow-up of ILD associated with RA. The PFT and BAL correlate only partially with lesion profusion or grading on HRCT, but they contribute valuable information about dynamic lung function and differential diagnoses (pneumonia, medication side effects).

(Thorax 2001;56:751-757)