RES phagocytosis in children with homozygous beta-thalassemia in relation to blood transfusion

In order to investigate the effect of blood transfusion on the RE cell function in thalassemia major, 14 children with homozygous beta thalassemia were studied prior to and 7 to 10 d following blood transfusion, when, according to previous studies, spleen reaches its minimum size. The denatured human albumin (DHA) low and large dose clearance techniques were used in order to estimate the maximum RES phagocytic capacity. It is shown that, despite the confirmed post-transfusion high hepatosplenic circulation, the RE cell phagocytic capacity is not significantly affected. Furthermore the RES phagocytic capacity of beta-thalassemics is shown to be significantly higher than that of normal controls, and this can probably be attributed to the RES hyperplasia accompanying the disease.     

Growth deceleration of children on inhaled corticosteroids is compensated for after the first 12 months of treatment

Timing and duration of linear growth suppression in children on long-term inhaled corticosteroids (ICS) are not entirely clear; we undertook a "pragmatic" study to determine growth of asthmatic children on long-term ICS managed by a flexible dosing step-down approach. Standard deviation scores of height (HSDS), height velocity (HVSDS), and body mass index (BMISDS) of pre-pubertal asthmatic children on maintenance therapy with either budesonide (BUD) or fluticasone propionate (FP) were calculated in a prospective open-label non-randomized study. Outcomes were recorded at initiation of ICS, 6, 12, 24, and 36 months, as applicable, and 6 months after ICS treatment discontinuation. Three hundred twenty-two children on BUD and 319 on FP were enrolled after the completion of 6-month treatment. The median (range) daily dose at initiation was 400 mcg (400-1,200) and 200 mcg (200-500), the final maintenance 200 mcg (200-400) and 100 mcg (100-200), respectively. In the first 6-12 months, a decrease in HSDS of approximately 18% below baseline values was noted (P < 0.01) that was restored to almost baseline average levels by 24 months, and slightly increased to above baseline during the third year. HVSDS showed a linear increase in both treatment arms (P < 0.01). No differences were found between the two treatment arms regarding HSDS, HVSDS, and BMISDS at any time point over the course of the study. In conclusion, growth deceleration of asthmatic children on maintenance ICS is compensated for after the first 12 months of treatment. This effect does not differ between BUD and FP treatment, despite some variation in the pattern of linear growth.     

Growth hormone (GH) responses to GH-releasing hormone-arginine testing in human immunodeficiency virus lipodystrophy

Prior studies suggest reduced overnight GH secretion in association with excess visceral adiposity among patients with HIV lipodystrophy (LIPO, i.e. with fat redistribution). We now investigate GH responses to standardized GHRH-arginine in LIPO patients (n = 39) in comparison with body mass index- and age-matched control groups [HIV patients without fat distribution (NONLIPO, n = 17)] and healthy subjects (C, n = 16). IGF-I [242 +/- 17; 345 +/- 38; 291 +/- 27 ng/ml (P < 0.05 vs. NONLIPO)] was lowest in the LIPO group. Our data demonstrate failure rates of 18% for the LIPO group vs. 5.9% for the NONLIPO group and 0% for the C group, using a stringent criterion of 3.3 ng/ml for peak GH response to GHRH-arginine (P < 0.05 LIPO vs. C). Using less stringent cutoffs, the failure rate in the LIPO group rises to 38.5% at 7.5 ng/ml. Among the LIPO patients, the peak GH response to GHRH-arginine was significantly predicted by visceral adipose tissue (P = 0.008), free fatty acid (P = 0.04), and insulin level (P = 0.007) in regression modeling controlling for age, body mass index, sc fat area, and triglyceride level. These data demonstrate increased failure rates to standardized stimulation testing with GHRH-arginine in LIPO patients, in association with increased visceral adiposity. The effects of low-dose GH should be assessed in the large subset of LIPO patients with abnormal GH stimulation testing.     

Antithrombin III treatment improves parameters of acute inflammation in a highly histoincompatible model of rat lung allograft rejection

BACKGROUND: Antithrombin III (AT-III) is an antithrombotic agent with known anti-inflammatory properties that is also known to attenuate acute inflammation, prevent ischemia-reperfusion injury, and disseminated intravascular coagulation (DIC) associated with sepsis and endotoxemia. Here, we examined the ability of AT-III to modify parameters of acute inflammation in a highly histoincompatible model of rat lung allograft rejection (AR). METHODS: After left single lung transplantations (BN-->Lew), recipient animals were treated i.v. with 50 U/kg of human AT-III (low dose group), 500 U/kg of human AT-III (high dose group), or normal saline (control group) on days 2 and 4 posttransplant. All animals were sacrificed on day 6, and several pathological categories of acute inflammation related to AR were scored (0-4). The effect of AT-III on concanavalin A (Con A)-stimulated rat spleen cell proliferation was also examined. RESULTS: The stage of AR, and the degrees of edema, hemorrhage, and necrosis were significantly reduced in the high dose group compared with the control group. AT-III significantly inhibited rat spleen cell proliferation in response to Con A, in a dose-dependent manner. Maximal inhibition was seen at 15 U/ml in culture. Identical inhibition of Con-A-stimulated cultures occurred in both serum free and serum-containing media, indicating that AT-III inhibition of Con-A-stimulated rat spleen cell proliferation is independent of its actions on thrombin. CONCLUSIONS: 1) AT-III treatment significantly improves parameters of acute inflammation seen in a highly histoincompatible model of rat lung AR. 2) AT-III inhibits in vitro T cell proliferation to the potent mitogen Con A, suggesting that protease inhibition may inhibit T cell activation in vitro. 3). The beneficial effects of AT-III on parameters of lung AR relate to the anti-coagulant, anti-inflammatory, and possibly immunoregulatory actions of AT-III.