The role of androgens or growth factors in the bone resorption process in recent spinal cord injured patients: a cross-sectional study.

STUDY DESIGN: This cross-sectional study compared the androgen and growth factor profiles and the bone turnover of patients with spinal cord injury (SCI) versus able-bodied controls (AB). OBJECTIVE: Determine whether androgens, GH, or either IGF-I or IGFBP-3, are implicated in bone turnover alteration in patients with recent SCI. SETTING: Propara Center, Montpellier, France. METHODS: In all, 16 men (31.3 years) with complete SCI, seven paraplegics and nine tetraplegics, who had sustained injury an average of 3 months earlier, and 12 AB who served as controls (27.5 years) participated. Androgens, growth hormone and its mediators were investigated. The bone resorption process was evaluated by urinary and plasma type I collagen C-telopeptide (CTXu, CTXp), while bone formation was evaluated by osteocalcin (OC) and bone alkaline phosphatase. RESULTS: Total testosterone (TT) and the free androgen index (FAI) were significantly lower in the SCI patients, whereas FSH was significantly higher (P<0.05). These hormonal variations were not related to the level of neurological lesion. There was no significant difference in GH, IGF-I, or IGFBP-3 levels. CTXu and CTXp indicated high bone resorption activity in the SCI patients (P<0.05). Regarding bone formation markers, only OC was affected by neurological lesion (P<0.05). Basal hormone levels did not correlate with markers of bone turnover. CONCLUSION: The high bone resorption process observed in SCI patients did not seem directly related to testicular endocrine abnormalities or an altered growth factor profile. Nevertheless, the reduced TT and FAI levels could be aggravating factors in the development of acute bone loss.

The intensity level of physical exercise and the bone metabolism response.

This study investigated the short-term effects of the intensity level of physical exercise on bone metabolism and related hormones. The responses of calciotropic hormones and bone biochemical markers were evaluated in seven male cyclists (mean age 24.4 years, range 20-39) during two 50-min cycling tests performed 15% below (-VT) and 15% above (+VT) the ventilatory threshold. In each test, venous blood samples were drawn at rest, at the 30th and 50th min of exercise, and after 15 min of recovery. For both intensity levels, no significant variation in calcium, 25-hydroxyvitamin D, 1.25-dihydroxyvitamin D, or cortisol level was observed. Intact parathyroid hormone (iPTH) level increased significantly after the last minute of the test (41%, p < 0.05) and peaked during the recovery (80%, p < 0.05) only in response to exercise performed at +VT. Serum phosphorus concentration rose during both tests, while albumin levels increased only at +VT. Concerning bone cell activity, osteocalcin, and type I-C telopeptide breakdown products transiently increased only in response to exercise performed at +VT (11% and 16.8%, respectively; p < 0.05). Bone alkaline phosphatase increased similarly for both intensity levels after 30 min (12%, p < 0.05) and 50 min (12% for -VT vs. 14% for +VT, p < 0.05). All markers of bone turnover returned to initial values during the recovery. In conclusion, a no-impact but intense and sustained exercise performed at +VT transiently stimulated bone turnover and iPTH secretion, suggesting the existence of a bone stimulation threshold. In addition to the well known effect of mechanical constraints, both the duration and intensity of exercise may induce changes in bone turnover.

Response of bone metabolism related hormones to a single session of strenuous exercise in active elderly subjects.

OBJECTIVE: To evaluate the effect of strenuous exercise on bone metabolism and related hormones in elderly subjects. METHODS: Twenty one active elderly subjects (11 men and 10 women; mean age 73.3 years) showing a mean theoretical Vo2max of 151.4% participated. Concentrations of plasma ionised calcium (iCa), serum intact parathyroid hormone (iPTH), 25-hydroxyvitamin D (25(OH)D), and 1.25-dihydroxy-vitamin D3 (1.25(OH)2D3), as well as the bone biochemical markers type I collagen C-telopeptide for bone resorption and osteocalcin and bone alkaline phosphatase for bone formation, were analysed before and after a maximal incremental exercise test. RESULTS: At basal level, iPTH was positively correlated with age (r = 0.56, p < 0.01) and negatively correlated with 25(OH)D (r = -0.50; p < 0.01) and 1.25(OH)2D3 (r = -0.47; p < 0.05). Moreover, 25(OH)D and 1.25(OH)2D3 levels were negatively correlated with age (r = -0.50, p < 0.01 and r = -0.53, p < 0.01, respectively). After exercise, iCa and 25(OH)D decreased (p < 0.001 and p = 0.01, respectively) while iPTH increased (p < 0.001). The levels of 1.25(OH)2D3, bone biochemical markers, haematocrit, and haemoglobin were unchanged. The variations in iCa and 25(OH)D were not related to age and/or sex. The iPTH variation was directly related to basal iPTH levels (p < 0.01) and indirectly related to age. CONCLUSIONS: In active elderly subjects, strenuous exercise disturbed calcium homeostasis and bone related hormones without immediate measurable effect on bone turnover. Although an increase in iPTH could have an anabolic action on bone tissue, our findings from our short term study did not allow us to conclude that such action occurred.

Changes in osteoprotegerin/RANKL system, bone mineral density, and bone biochemicals markers in patients with recent spinal cord injury.

This study analyzed the temporal and regional variations in bone loss and explored bone cell activities via biochemical markers during an extended follow-up in patients with spinal cord injury (SCI). In parallel, the possible role of the osteoprotegerin (OPG)/RANKL system in disuse osteoporosis was investigated. Seven male patients with acute and complete SCI (31.3 +/- 9.5 years) and 12 able-bodied (AB) men (26.9 +/- 4.2 years) participated in the study. Measurements were performed 16, 24, 36, 48, and 71 weeks after injury. At week 16, marked calcium homeostasis disturbance and a concomitant increase in bone resorption markers were observed, reflecting an intense bone degradation process. Resorption activity decreased continuously with time. Contrasting with the great rise in the resorption markers, the bone formation markers showed little variation. During the period of investigation, a loss in bone mineral density (BMD) was demonstrated for the total body (-4.3%), pelvis (-15.7%) and lower limbs (-15.2%), whereas BMD did not change at the lumbar spine, upper limbs, or skull. At all stages, SCI patients had lower serum RANKL levels and higher serum OPG levels than did AB controls, but no significant variation with time was observed for either cytokine. These findings suggest that bone resorption persisted long after SCI and specifically affected BMD at sublesional sites. The marked modification of serum OPG/RANKL levels in SCI patients suggests that this system is affected, in disuse osteoporosis. However, the precise biologic role of the OPG/RANKL system in the bone tissue of SCI patients has yet to be determined.

Effects of physical activities that induce moderate external loading on bone metabolism in male athletes.

Sports characterized by little or moderate weight bearing or impact have a low osteogenic effect. However, the action of such sports on bone turnover remains unclear. The objective of this study was to determine the effect on bone remodelling of physical activities that induce moderate external loading on the skeleton. Thirty-eight male athletes aged 18-39 years (cyclists, n = 11; swimmers, n = 13; triathletes, n = 14) and 10 age-matched sedentary controls aged 22-35 years participated in the study. The study combined measurement of bone mineral density by dual-energy X-ray absorptiometry and bone turnover assessment from specific biochemical markers: serum bone-specific alkaline phosphatase, osteocalcin, urinary type I collagen C-telopeptide and calcium. Compared with the controls and swimmers, adjusted bone mineral density was higher (P < 0.05) in triathletes at the total proximal femur and lower limbs. No differences in bone mineral density were found between cyclists, swimmers and controls. Compared with controls, osteocalcin was higher (P < 0.05) in triathletes and swimmers and urinary type I collagen C-telopeptide was higher in swimmers only. Serum bone-specific alkaline phosphatase was lower (P < 0.05) in cyclists than in all other groups. In conclusion, an osteogenic effect was found only in triathletes, mainly at bone sites under high mechanical stress. Bone turnover differed in athletes compared with controls, suggesting that bone turnover may be sport-practice dependent. Despite some encouraging observations, it was not possible to show that changes in the bone remodelling process were sport-discipline dependent.

Effects of successive running and cycling on the release of atrial natriuretic factor in highly trained triathletes.

AIM: To evaluate the influence of successive running and cycling on both exercise-induced arterial hypoxemia (EIAH) and atrial natriuretic factor (ANF) release, 5 triathletes performed 2 separate exercise trials. METHODS: One trial consisted of a 20-min+20-min successive cycle-run exercise (C(1)-R(2)) and the other consisted of a 20-min+20-min successive run-cycle exercise (R(1)-C(2)). Arterial oxygenation (PaO(2)) and ANF were determined at pre-exercise, at the end of each 20-min segment of exercise and after 10 min of recovery. RESULTS: EIAH was noted during C(1)-R(2) and R(1)-C(2) trials. A higher EIAH was observed during running compared with cycling performed in the 1(st) position (R(1) vs C(1)) in the succession. In contrast, no difference was observed between successive running and successive cycling (R(2) vs C(2)), (-10.6+/-7.0 vs -15.6+/-4.0 mmHg for C(1)-R(2) and -20.9+/-6.0 vs -16.2+/-2.4 mmHg for R(1)-C(2)). ANF showed no difference between cycling and running performed in first position, whereas a significantly lower ANF was observed during successive cycling compared with successive running (C(2) vs R(2)) (19.9+/-3.72 vs 36.2+/-6.4 pmol.L(-1)). During recovery, neither PaO(2) nor ANF plasma returned to baseline level after either trial. CONCLUSION: This study provides new information on some of the physiological modifications that occur during multi-sports. Specifically, the impact of the modality of the successive exercise on ANF release and body fluid regulation was observed. Cycling as the successive exercise seems to cause lower ANF release than does running.

Attenuated ANF response to exercise in athletes with exercise-induced hypoxemia.

Some highly trained endurance athletes develop an exercise-induced hypoxemia (EIH) at least partially due to a hemodynamic factor with a potential stress failure on pulmonary capillaries. Atrial natriuretic factor (ANF) is a pulmonary vasodilatator and its release during exercise could be reduced with endurance training. We hypothesized that athletes exhibiting EIH, who have a greater training volume than non-EIH athletes, have a reduced ANF release during exercise explaining the pathophysiology of EIH. Ten highly trained EIH-athletes (HT-EIH), ten without EIH (HT-nEIH), and nine untrained (UT) males performed incremental exercise to exhaustion. No between group differences occurred in resting ANF plasma levels. In contrast to HT-nEIH and UT (p < 0.05), HT-EIH showed a smaller increase in ANF concentration between rest and maximal exercise (HT-EIH: 8.12 +/- 0.69 vs. 14.1 +/- 1.86 pmol x l (-1); HT-nEIH: 10.46 +/- 1 vs. 18.7 +/- 1.8 pmol x l (-1); UT: 6.23 +/- 0.95 vs. 20.38 +/- 2.79 pmol x l (-1)). During the recovery, ANF levels decreased significantly in HT-nEIH and UT groups (p < 0.05). Electrolyte values increased in all groups during exercise but were higher in both trained groups. In conclusion, this study suggested that ANF response to exercise may be important for exercise-induced hypoxemia.

Competitive season of triathlon does not alter bone metabolism and bone mineral status in male triathletes.

This longitudinal study evaluated the effects of a triathlon season on bone metabolism and hormonal status. Seven male competitive triathletes (mean age 19.3 years, range 18 - 20) with 5.0 +/- 0.3 years of competition experience were tested twice during the season: at the beginning of training and 32 weeks later. Total and regional bone mineral density (BMD) was determined by dual-energy X-ray absorptiometry, while bone turnover was evaluated by specific biochemical markers: bone-specific alkaline phosphatase (B-ALP), osteocalcin, and urinary type I collagen C-telopeptide. In addition, sexual, calciotropic and somatotropic hormones were also analyzed. After 32 weeks, a BMD increase was found at the lumbar spine (1.9 %; p = 0.031) and skull (3.1 %; p = 0.048), while no variation was observed for total body or at the proximal femur. The B-ALP level decreased (-23.2 %; p = 0.031), but no variation was found for the other bone markers. 1.25 (OH) (2)D3, IGF-1 and the bioavailability IGF-1 index (IGF-1/IGFBP-3) increased by 18.3 % (p = 0.047), 29 % (p = 0.048), 33 % (p = 0.011), respectively, while PTH, testosterone, IGFBP-3 and cortisol concentrations were unchanged. In conclusion, the triathlon season had a moderately favourable effect on BMD, although a slowing down of bone formation activity was observed. No variation in hormonal levels was observed that could have limited the effects of exercise on bone tissue.

Basophil releasability in young highly trained and older athletes.

PURPOSE: Exercise-induced hypoxemia in highly trained athletes is associated with an increase in histamine release during exercise. The cells most implicated in blood histamine release are basophils. The aim of this study was to determine whether high-level endurance training induces modifications in histamine releasability from human basophils. METHODS: Seven young highly trained athletes (YA) [aged 26.1+/-1.3 yr (mean +/- SEM)] and seven master athletes (MA) (64.4+/-4.1 yr), all known to develop exercise-induced hypoxemia, were respectively compared with seven young untrained men (YC) (23.0+/-1.5 yr) and seven older untrained men (OC) (61.6+/-1.3 yr). During an incremental exhaustive exercise, blood samples for measurement of anti-IgE-induced histamine release from leukocytes were drawn at rest, VO2max, and recovery. RESULTS: Basophils from "leukocyte-rich" supernatant in YA and MA showed significantly higher histamine release induced by anti-IgE (1 microg x mL(-1) than, respectively, YC (P<0.01) and OC (P<0.05) at rest, VO2ax (P<0.01), and recovery (P<0.01). Basophils in YA and MA also showed a histamine release induced by anti-IgE that was higher at VO2max than at rest (respectively. P<0.01 and P<0.05), but this change was not found in the control groups. CONCLUSION: In conclusion, the basophils in highly trained endurance athletes, both young and older, showed higher anti-IgE-induced histamine release than those of untrained men. This effect of high-level training seemed to be potentiated by exercise.

Interleukin-4 and interleukin-10 are chondroprotective and decrease mononuclear cell recruitment in human rheumatoid synovium in vivo.

We used the severe combined immunodeficient (SCID) mouse model to assess the effect of interleukin-4 (IL-4) or IL-10 injection on cartilage degradation and mononuclear cell (MNC) recruitment to human rheumatoid synovium in vivo. Human rheumatoid synovium and cartilage from five rheumatoid arthritis patients, obtained after joint replacement surgery, were engrafted subcutaneously to 6-8-week-old SCID CB17 mice. Synovial tissues were injected with recombinant human IL-4 (rhIL-4, 100 ng; rhIL-10, 100 ng), both cytokines, or tumour necrosis factor-alpha (TNF-alpha) (1000 U), or phosphate-buffered saline twice a week for 4 weeks. The graft was removed and immunochemical analysis was carried out to assess intracellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin expression. Moreover, cartilage degradation was assessed through the quantification of the erosion surface on a computerized image of the engrafted cartilage at high power view. MNC recruitment in the synovial tissue was determined by labelling blood MNC with indium-111 before their intraperitoneal injection. The activity obtained in the region of the graft were determined with a gamma camera 72 hr postinjection. The results are expressed as a percentage of initial injected activity. After 4 weeks we observed a decrease of cartilage area in controls (77 +/- 8%), inhibited after injection of IL-4, IL-10, or both cytokines (90 +/- 3%, 89.1 +/- 4%, 89.2 +/- 5% respectively), and 57 +/- 17% after TNF-alpha injection. The % MNC activity in the graft decreased to 77 +/- 81% (NS), 9 +/- 4% (P < 0.003) and 19 +/- 6% (P < 0.007) compared with untreated synovial tissue after treatment with IL-4, IL-10, or both cytokines, respectively. Moreover, IL-10 but not IL-4 decreased the expression of ICAM-1 but not VCAM-1 or E-selectin by synovial cells. These results suggest that IL-10 and IL-4 could have chondroprotective properties, and that IL-10 but not IL-4 inhibits MNC traffic towards the synovial tissue efficiently.

Mononuclear cell retention in rheumatoid synovial tissue engrafted in severe combined immunodeficient (SCID) mice is up-regulated by tumour necrosis factor-alpha (TNF-alpha) and mediated through intercellular adhesion molecule-1 (ICAM-1).

The aim of this study was to assess regulation of mononuclear cell (MNC) traffic to human synovial tissue by TNF-alpha and IL-1 and the involvement of ICAM-1 in MNC retention in rheumatoid synovial tissue. Human rheumatoid arthritis synovium was engrafted subcutaneously in 6-8 week-old SCID/CB17 mice. Three weeks later, we injected 20 x 10(6) human peripheral blood mononuclear cells (PBMC) previously labelled with 111indium intraperitoneally into mice containing control or cytokine-injected grafts. Total body scintigraphy was performed 72 h postinjection. The graft was removed and immunochemical analysis carried out to assess ICAM-1, vascular cell adhesion molecule-1 (VCAM-1) and E-selectin expression. In some experiments, mice were treated intravenously with 500 micrograms MoAb anti-ICAM-1 (BIRR-1) or an isotype-matched control MoAb before introduction of MNC. TNF-alpha, but not IL-1 alpha, enhanced MNC retention in the rheumatoid synovial graft 72 h post-injection (graft activity 989 +/- 1227 ct/min per 200 pixels or 3.36 +/- 4.16% of initial injected activity versus 411 +/- 157 ct/min per 200 pixels or 1.13 +/- 0.45% in controls; P < 0.03). TNF-alpha enhanced ICAM-1 expression by synovial cells and endothelial cells, whereas VCAM-1 or E-selectin expression was not enhanced on either cell type. After MoAb treatment of ICAM-1, synovial lymphocyte recruitment of TNF-alpha-treated mice decreased significantly to levels below that of control mice (160 +/- 97 ct/min per 200 pixels, 0.54 +/- 0.33%; P < 0.01). Mononuclear cell retention in rheumatoid synovial tissue engrafted into SCID mice was up-regulated by TNF-alpha and blocked by MoAb to ICAM-1. These results suggest that ICAM-1 is involved in mononuclear cell retention in rheumatoid synovium.

In vivo migration of radiolabelled lymphocytes in rheumatoid synovial tissue engrafted in SCID mice: implication of beta 2 and beta 7-integrin.

OBJECTIVE: Integrin-adressin binding is a critical step in lymphocyte attachment to target tissues. The lymphocyte function associated antigen (LFA-1)/intercellular adhesion molecule-1 (ICAM-1) pathway has been shown to be involved in the homing of lymphocytes to arthritic joints in animal models. The mucosal recognition system [alpha E beta 7/E-cadherin, alpha 4 beta 7/mucosal vascular adressin cellular adhesion molecule 1 (MADCAM-1)] has been implicated in the autoimmune process of nonobese diabetic mice and in rheumatoid arthritis (RA). We developed a model for in vivo study of radiolabelled lymphocyte circulation and attachment to human engrafted rheumatoid synovium, and studied the involvement of LFA-1 and alpha E beta 7 integrin. METHODS: We engrafted human RA or osteoarthritis (OA) synovium subcutaneously in 6-week-old SCID/CB17 mice. Three weeks later, we injected intraperitoneally 20 x 10(6) human peripheral blood lymphocytes (PBL) labelled with 3 mCi 99mtechnetium hexamethyl propylenamine oxime. A mouse total body scintigraphy was obtained 20 h postinjection. The same protocol was performed after pretreatment of the PBL with monoclonal antibodies (Mab) against CD11a (25-3) or against alpha E beta 7 human mucosyl lymphocyte marker 1. RESULTS: PBL migrated in the rheumatoid synovial graft 20 h postinjection (activity in the region of interest of the graft: 7699 +/- 4383 cpm/200 pixel or 4.43 +/- 2.65% of initial activity) versus OA engrafted synovial tissue (1453 +/- 1137 or 0.74 +/- 0.6% of initial activity), p = 0.007. The homing to the engrafted rheumatoid synovial tissue of PBL from healthy subjects was not significantly different from the migration of PBL from patients with RA. A Mab against alpha E beta 7 significantly decreased lymphocyte attachment to rheumatoid synovial tissue (3094 +/- 3808 cpm/200 pixel or 2.65 +/- 2.4% of injected activity), p < 0.03. The same results were obtained with Mab against CD11a (5007 +/- 4190 cpm/200 pixel or 2.27 +/- 1.2%), p < 0.01. Our results show increased blood lymphocytes homing to rheumatoid synovial tissue engrafted in SCID mice versus OA tissue. CONCLUSION: The data suggest that both LFA-1 and mucosal recognition integrin alpha E beta 7 are involved in lymphocyte binding to target tissues in RA.

In vivo migration of tonsil lymphocytes in rheumatoid synovial tissue engrafted in SCID mice: involvement of LFA-1.

Integrin-adressin binding is a critical step in lymphocte attachment to target tissues. The mucosal recognition systems (alpha E beta 7, alpha 4 beta 7, MADcam-1) have been implicated in the autoimmune process in rheumatoid arthritis. We developed a model for in vivo study of radio-labelled lymphocyte circulation and their attachment to human rheumatoid synovium. We studied the homing of tonsil lymphocytes, considered as mucosal lymphocytes, and the involvement of alpha E beta 7 integrin and LFA1 in the homing of tonsil lymphocytes. We engrafted human rheumatoid synovium subcutaneously in 6 week old SCID CB17 mice. Three weeks later, we injected intraperitoneally 20 IO6 human peripheral blood or tonsil mononuclear cells, previously labelled with 3 mCFi HMPAO-99mTc. A mouse total body scintigram was obtained 20 h postinjection. The same protocol was performed after treatment of the MNC and mAb against LFA-1 (CD11a) or alpha E beta 7 (CD103). Tonsil MNC retention in the rheumatoid synovial graft 20 h post-injection was enhanced compared to blood MNC (12731 +/- 8297cpm/200 pixel) versus 5982 +/- 4713cpm/200 pixel, p < 0.05). A monoclonal antibody against LFA 1 decreased the activity in the graft (4152 +/- 1287 cpm/200 pixel), p < 0.05. No significant difference in tonsil MNC attachment to rheumatoid synovial tissue was observed with a mAb against alpha E beta 7 (8057 +/- 5009 cpm/200 pixel). Our results showed an increase in radiolabelled mucosal MNC migration in synovial tissue engrafted in SCID mice compared with blood MNC. Moreover, the date suggest that LFA-1 but not the alpha E beta 7 integrin is involved in tonsil MNC binding to synovial tissue in RA.

The use of technetium-99m hexamethylpropylene amine oxime labelled granulocytes with single-photon emission tomography imaging in the detection and follow-up of recurrence of infective endocarditis complicating transvenous endocardial pacemaker.

In this case report we present a patient with a recurrence of subacute bacterial infectious endocarditis (IE) complicating a transvenous endocardial pacemaker. Technetium-99m hexamethylpropylene amine oxime (99mTc-HMPAO) labelled granulocytes were used for diagnosis and follow-up under medical treatment only, since surgical removal of the pacemaker lead was ruled out because of the general condition of the patient. Single-photon emission tomography (SPET) imaging displayed the active lesion previously suspected on echography. At the end of antibiotic therapy, SPET indicated a favourable disease outcome whereas echocardiographic abnormalities remained nearly unchanged. The medical treatment had eradicated the IE, and the patient did well for more than 1 year thereafter.

Radiolabelled lymphocyte migration in rheumatoid synovitis.

OBJECTIVES: To study the ability of technetium-99m hexamethyl propylene amineoxime (HMPAO) labelled lymphocyte scintigraphy to quantify synovial inflammation, and to analyse the kinetics of lymphocyte retention in the joints of patients with rheumatoid arthritis (RA). METHODS: After isolation of the lymphocytes, the cells were radiolabelled in vitro with 250 MBq 99mTc-HMPAO. The scans were performed 30 minutes, three hours and 20 hours after injection. RESULTS: An increase of the scintigram signal obtained at 20 hours was associated with a high joint swelling and joint pain score (F test = 3.07, p < 0.002), but not with the radiological score. A positive joint scintigram was predictive of active synovitis. Although the scintigram variation over time did not reach statistical significance, the kinetics of the scintigram signal tended to differ according to the disease duration: in early RA, active arthritis could be clearly imaged as early as 30 minutes, increased at three hours and the signal intensity persisted at 20 hours. In contrast, in long standing disease, the affected joints were imaged at 30 minutes, persisted unchanged at three hours, and the scintigram score decreased significantly at 20 hours. CONCLUSIONS: The study shows that 99mTc-HMPAO joint scintigraphy may be used to detect and to localise active rheumatoid arthritis.

Histamine and exercise-induced hypoxemia in highly trained athletes.

To determine whether exercise-induced hypoxemia in extreme athletes results from an increase in histamine level during maximal incremental exercise, seven young athletes [YA; age 22.2 +/- 1.23 (SE) yr] and seven master athletes (MA; age 66.2 +/- 2.94 yr), all of whom were known to develop exercise-induced hypoxemia, were compared with age-matched control groups (young controls and older controls, respectively). During maximal incremental exercise, blood samples for arterial blood gas analysis and for plasma and total histamine were drawn at rest and at 50, 75, and 100% of maximal O2 uptake. The percentage of histamine released (%H) was calculated from plasma and total histamine samples. In all athletes (MA and YA groups), exercise induced an increase in %H with a concomitant decrease in arterial PO2 (PaO2); in control groups there was no change in either histamine levels or PaO2. When the data for the YA and MA groups were combined, a correlation was observed between the increase in %H and the drop in PaO2. Nevertheless, further studies are required to establish whether histamine plays a causative role in hypoxemia or is a response to injury.

[Scintigraphy with radiolabeled granulocytes for the detection of peripheral septic osteoarticular sites]. / Scintigraphie aux polynucléaires marqués dans la détection des foyers septiques ostéoarticulaires de siège périphérique.

Radiolabeled granulocyte scintigraphy is a recently introduced technique for detecting osteoarticular infections. Technetium-99m-labeled hexamethylpropylamineoxime (HMPAO), in use since 1986, provides excellent resolution with less radiation exposure than indium-111. Elimination of lymphocytes provides further improvements in image quality and safety, making the technique suitable for use in children. The authors prospectively studied 30 scintigraphies performed with isolated autologous 99mTc-HMPAO-labeled granulocytes to evaluate suspected osteoarticular infection. Image quality was outstanding. In peripheral sites, infection manifested as a focus of increased uptake visible in all three phases (30 min, 3 hours and 18 hours after the injection). Performance was excellent, with 11 true-positive scans, 14 true negative scans, 4 false-positive scans (including two ascribable to recent surgery), and one false-negative scan. Among the 28 evaluable cases, positive predictive value was 85%, negative predictive value was 90%, and sensitivity, specificity, and accuracy were 92%, 88%, and 89%, respectively. The only limitation to routine use of this technique is the need for in vitro granulocyte separation which is time-consuming and requires special precautions to preserve granulocyte function. Nevertheless, these data demonstrate that 99mTc-HMPAO-labeled granulocyte scintigraphy is of value for the detection of osteoarticular infections in patients without chronic inflammatory joint disease.

Functional characteristics of bronchial epithelium obtained by brushing from asthmatic and normal subjects.

Airways epithelial cells may be involved in the pathogenesis of asthma, but their role remains to be determined. Epithelial cells can release large amounts of 15-hydroxy-eicosatetranoic acid (15-HETE) and smaller amounts of prostaglandin E2 (PGE2) as well as fibronectin, a mediator involved in epithelial repair after injury. Epithelial cells obtained after bronchial brushing of 16 asthmatic (age 38 +/- 5 yr) and 11 normal subjects (age 36 +/- 5 yr) were studied. The percentage of epithelial cells was assessed by immunocytochemistry using an anti-cytokeratin antibody. The viability of the cells was assessed by trypan blue exclusion. The release of 15-HETE PGE2 and fibronectin was studied in resting cells and after A23187 calcium ionophore stimulation. Epithelial cells always comprised more than 86% of cells recovered, and the viability of epithelial cells was significantly (p < 0.001, Mann-Whitney U test) greater in normal subjects (54 +/- 5%) compared with asthmatic subjects (13 +/- 1%). The release of 15-HETE and fibronectin by resting epithelial cells was significantly greater in asthmatics (p < 0.05, Mann-Whitney U test) than in normal subjects. A23187 significantly (p < 0.05, Wilcoxon W test) increased the release of 15-HETE and fibronectin. There was no significant difference in the release of PGE2 by resting cells from either asthmatics or normal subjects, but challenge with A23187 induced a significant (p < 0.03, Wilcoxon W test) increase in PGE2 from cells of asthmatics but not from cells of normal subjects. This study shows that epithelial cells are activated and less viable in asthma and suggests a role for these cells in asthma.