Alveolar Macrophage Release of Tumor Necrosis Factor-α in Chronic Alcoholics without Liver Disease

Alcohol is an immunosuppressive drug, and chronic abuse has been associated with increased susceptibility to a variety of infections, including bacterial pneumonia and tuberculosis. Alveolar macrophages are the resident phagocytes of the lung and play a central role in lung host defenses against infection ranging from direct antibacterial activity to the release of proinflammatory cytokines such as tumor necrosis factor-α (TNFα). TNFα, in particular, plays a key role in the development of the early inflammatory response. In this study, we investigated the effects of chronic alcohol consumption on alveolar macrophage release of TNFα in vitro. We prospectively studied lipopolysaccharide (LPS)-stimulated release of TNFα from alveolar macrophages obtained from bronchoalveolar lavage fluid (BALF) in 22 alcoholic (18 smokers, 4 nonsmokers) and 7 nondrinking healthy volunteers (3 smokers, 4 nonsmokers). The total number of cells recovered by bronchoalveolar lavage (BAL) and their differential distribution were not significantly different in alcoholics versus controls (43 ± 8 × 10⁶ and 39 ± 13 × 10⁶, respectively). However, the total number of cells recovered from BALF was significantly higher in smokers (51 ± 8 × 10⁶) than in nonsmokers (19 ± 5 × 10⁸). Spontaneous (basal) release of TNFα by alveolar macrophages was the same in alcoholics and controls. In contrast, LPS-stimulated release of TNFα was significantly suppressed in alcoholics compared with that of controls (1343 ± 271 vs. 3806 ± 926 U TNF/ml/10⁶ cells, respectively, p < 0.015). When controlled for smoking, LPS-stimulated TNFα production was suppressed in alcoholic nonsmokers (563 ± 413 U TNF/ml/10⁶) compared with control nonsmokers (5113 ± 1264 U TNF/ml/10⁶). LPS-stimulated TNFα production was also less in control smokers (2063 ± 386 U TNF/ml/10⁶ cells) than in control nonsmokers (5113 ± 1264 U TNF/ml/10⁶ cells). There was no difference in TNFα production between smoking alcoholics and smoking control subjects. We conclude that chronic alcohol consumption significantly suppresses LPS-stimulated alveolar macrophage production of TNFα. This effect is obscured if the subject also smokes. Because TNFα production is an important element in host defense, this may explain, in part, the susceptibility of chronic alcohol abusers to a variety of infections.     

Hyaluronan (hyaluronic acid) in lung lavage of asbestos-exposed humans and sheep

The concentration of hyaluronan was measured in the bronchoalveolar lavage fluid (BALF) of 18 control subjects and 27 workers from the asbestos mills and mines of Québec, 9 without asbestosis and 18 with asbestosis. Hyaluronan was also measured in the BALF of 9 control sheep exposed to 100 ml phosphate-buffered saline (PBS) at 10 day intervals for 39 months, and 13 sheep exposed at the same intervals to 100 mg chrysotile in 100 ml PBS for 24 months. At month 24, the asbestos-exposed sheep were classified into 3 groups: (A) 4 sheep exposed to PBS alone, (B) 4 sheep exposed to 10 mg chrysotile asbestos every 10 days, and (C) 5 sheep exposed to 100 mg chrysotile asbestos every 10 days for 15 months. The BALF hyaluronan averaged 53.9 ± 7.4 ng/ml in human controls, 67.5 ± 10.3 ng/ml in asbestos-exposed workers without asbestosis, and 206 ± 83 ng/ml in workers with asbestosis (p < 0.05 vs. normal). In the control sheep, BALF hyaluronan was 34.7 ± 6.9 ng/ml, and it was 31.5 ± 17.8 ng/ml in the low-dosage asbestos-exposed group (A), 83.0 ± 27.7 ng/ml in the intermediate-dose group (B), and 248.0 ± 134.7 ng/ml in the high-dosage group (C) (p < 0.05 vs. controls). In contrast, the release of plasminogen activator, a protease that may play a role in limiting the fibrotic process, was increased in group A, but not in groups B and C. In conclusion, BALF hyaluronan constitutes an indicator of lung interstitial tissue changes that may reflect the activity of the fibrosing alveolitis associated with chronic asbestos exposure. Offprint requests to: A. M. Cantin     

Blockade of neutrophil responses in aspiration pneumonia via ELR-CXC chemokine antagonism does not predispose to airway bacterial outgrowth

Pneumonia associated with aspiration of bacterial-laden gastric contents is characterized by Glu-Leu-Arg (ELR)-CXC chemokine (e.g., CXC2L1, CXCL8) expression leading to local neutrophil sequestration. This neutrophil response is designed to be protective, but overly aggressive responses can be pathogenic in themselves. Herein we assessed whether blocking neutrophil responses in a guinea pig model of aspiration pneumonia would foster airway bacterial growth. Guinea pigs (n = 5) were challenged intranasally with saline, acidified saline or acidified gastric contents (35 mg/kg body weight, pH 2.0) and treated subcutaneously with 250 μg/kg of the human ELR-CXC chemokine antagonist CXCL8_(3–72)K11R/G31P (G31P) or saline. After 20 h the animals' airway inflammatory responses and bacterial burdens were assessed. A loss of vascular integrity was apparent in the lungs of the saline-treated aspiration pneumonia animals (12.07+/?1.3% of the pleural surfaces exhibited hemorrhagic consolidation, 4.6 × 10⁶ RBC/ml bronchoalveolar lavage fluid [BALF]), as was a pulmonary neutrophilia. The BAL fluids contained gram-negative and -positive bacteria (total load, 6.3+/?3.2 × 10⁷ CFU/ml BALF) that are associated with nosocomial infections in humans. The G31P-treatments attenuated the pulmonary vascular complications (2.27+/?0.5% pleural surface hemorrhagic consolidation, 0.46 × 10⁶ RBC/ml BALF), and reduced the pulmonary neutrophilia by ≥86%. The G31P-treatments did not lead to significant changes in the airway bacterial loads (total load, 3.46+/?1.8 × 10⁷ CFU/ml BALF). This data indicates that attenuation of the pulmonary neutrophil response in aspiration pneumonia reduces pathology very significantly but does not reduce the efficiency of pulmonary bacterial clearance.     

Effects of acetazolamide on kidney function in Type 1 (insulin-dependent) diabetic patients with diabetic nephropathy

Summary We investigated the effects of 3 days treatment with acetazolamide 250 mg three times daily on kidney function in 8 Type 1 (insulin-dependent) diabetic patients with nephropathy, and in 7 healthy subjects in a double-blind placebo controlled cross-over study. Glomerular filtration rate and extracellular fluid volume were measured with the single injection ⁵¹Cr-EDTA technique and fluid flow rate from the proximal tubules was determined by measurement of the renal lithium clearance. A 24% decline in glomerular filtration rate was observed in both groups during acetazolamide treatment (control subjects: 108±11 vs 82±9 ml/min, p<0.02, diabetic patients: 71±19 vs 54±14 ml/min, p<0.01). The renal lithium clearance (ml/min) remained about the same (control subjects: 22±6 vs 27±8, NS, diabetic patients: 14±5 vs 15±4, NS). Absolute proximal tubular reabsorption of water (ml/min) was reduced by about one-third (control subjects: 85±11 vs 56±7, p<0.02, diabetic patients: 55±17 vs 37±6, p<0.02), and fractional proximal reabsorption of water and sodium (%) declined (control subjects: 79±5 vs 67±8, p<0.02, diabetic patients: 79±5 vs 72±6, p<0.02). Renal sodium clearance and distal fractional reabsorption of sodium was unchanged. Extracellular fluid volume declined by 10% in both groups (p<0.02). Albuminuria and fractional albumin clearance decreased significantly in the nephropathic patients (p<0.02). Our study suggests that the effects of acetazolamide on kidney function are similar in healthy subjects and patients with diabetic nephropathy.     

Efficacy of serum procalcitonin in evaluating severity of community-acquired pneumonia in childhood

Microbe-specific diagnosis of community-acquired pneumonia (CAP) in childhood is difficult in clinical practice. Chest radiographs and non-specific inflammatory markers have been used to separate presumably bacterial from viral infection but the results have been inconsistent. The aim of the present study was to evaluate the usefulness of procalcitonin (PCT) in assessing the severity as well as the bacterial or viral aetiology of CAP. Serum PCT was measured by an immunoluminometric assay in 100 patients with CAP; 26 were treated as inpatients and 74 as outpatients. The pulmonary infiltrate was considered to be alveolar in 62 and interstitial in 38 cases, according to the radiological diagnosis. The bacterial and viral aetiology of pneumonia was studied by an extensive serological test panel. No differences were found in PCT concentrations between the 4 aetiological (pneumococcal, atypical bacterial, viral, unknown) and the 3 age (< 2, 2-4 and > or = 5 y) groups. Serum PCT was >0.5 ng/ml in 69%, >1.0 ng/ml in 54% and >2.0 ng/ml in 47% of all patients. PCT was higher in patients that were admitted than as outpatients (medians 17.81 vs 0.72 ng/ml, respectively, p<0.01) and higher in alveolar than in interstitial pneumonia (medians 9.43 vs 0.53 ng/ml, respectively, p<0.01). In conclusion, serum PCT values were found to be related to the severity of CAP in children even though they were not capable, at any level of serum concentration, to differentiate between bacterial and viral aetiology.     

Serum levels of soluble CD44 variant isoforms are elevated in rheumatoid arthritis

Serum levels of soluble CD44 variant proteins including sequences encoded by exon v5 and exon v6 (sCD44v5, sCD44v6) were determined in patients with inflammatory rheumatic diseases: 56 with rheumatoid arthritis (RA⁺) and 31 with miscellaneous inflammatory rheumatic diseases (MIRD). There were very significantly higher serum levels of sCD44v5 and sCD44v6 in patients with RA' than in those with MIRD (RA⁺ to MIRD: sCD44v5: 81 ± 54 ng/ml to 33 ± 13 ng/ml; sCD44v6: 237 ± 124 ng/ml to 166 ± 53 ng/ml; bothP0.001). In RA⁺ elevated serum levels of sCD44v5 were correlated with the inflammatory activity of disease. In 17 patients with RA⁺ three or four follow-up measurements of sCD44v5 were performed within 6 months. The development of sCD44v5 serum levels reflected the clinical course of disease in the patients investigated.     

Angiotensin Converting Enzyme in Sarcoidosis and in Silicosis

Angiotensin converting enzyme(ACE) activities of broncho-alveolar lavage fluid(BALF) and serum in patients with sarcoidosis and with silicosis were measured. Serum ACE was measured by enzymic assay and radioimmunoassay. There was a close relationship between ACE activity and content (r=0.78). Serum ACE activities in patients with active sarcoidosis (37.5 ± 11.1 nmol/min/ml, mean ± SD) and with silicosis (25.5 ± 9.3) were significantly elevated from the control (18.6 ± 6.0). BALF ACE activities in the control, patients with active sarcoidosis and with silicosis were 0.23 ± 0.19 nmol/min/ml, 0.94 ± 0.97 and 0.38 ± 0.05, respectively. BALF ACE in patients with active sarcoidosis and with silicosis were significantly different from the control. When BALF ACE was corrected by the cell count of alveolar macrophage (per 10⁶ cells), activity was significantly different from control only in the patients with sarcoidosis. Moreover, only the alveolar macrophages in sarcoidosis were stained by immunofluorescence and immunocytochemistry using rabbit anti-human ACE antibody. Induction of ACE in alveolar macrophage might have an important role for the activity or progression of sarcoidosis.     

Increased Levels of Circulating ICAM-1, E-Selectin, and IL-2 Receptors in Celiac Disease

Adhesive interactions between endothelium and circulating cells are crucial for the development of inflammatory reactions. We found significantly higher serum levels of soluble intracellular adhesion molecule-1 (sICAM-1, 492.5 ± 22.1 ng/ml) in patients with active celiac disease (including IgA-deficient patients) than in patients on a gluten-free diet (335.7 ± 20.0 ng/ml) (P < 0.001) and healthy controls (207.4 ± 11.2 ng/ml) (P < 0.001). The concentration of soluble E-selectin in sera from celiac patients (37.2 ± 3.4 ng/ml) was also higher (P < 0.001) than in sera from healthy controls (15.5 ± 0.7 ng/ml) but, in contrast to sICAM-1, it remained high in the patients after treatment (30.2 ± 2.7 ng/ml). Interestingly, the concentration of circulating soluble interleukin-2 receptors, molecules indicating lymphocyte activation, was only increased in sera from patients with active celiac disease (2943.0 ± 214.1 pg/ml), and the level in sera from treated patients and healthy controls was comparable (1936 ± 349 and 1416 ± 111.7 pg/ml). The elevated serum level of soluble cell adhesion molecules could be used as a supplementary, noninvasive procedure for monitoring intestinal immune reactions.     

Bronchoalveolar lavage fluid alteration in antioxidant and inflammatory status in lung cancer patients

Background

Increased oxidative and inflammatory markers have been reported in lung cancer patients, but relatively few studies have investigated the presence of antioxidants both in the local lung environment and in the systemic circulation. Furthermore, it is hypothesized that the immune system activation in vivo is regulated by the redox environment.

Objectives

To investigate local and systemically circulating antioxidant and inflammatory mediators in lung cancer patients and potential correlations between them.

Methods

Forty two male patients (mean age 65 ± 8 years) with primary lung cancer were studied. Sixteen age and smoking history matched male subjects without any evidence of malignancy served as controls. Total antioxidant status (TAS) and glutathione (GSH), as well as interleukin-1a (IL-1a), interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) were measured in bronchoalveolar lavage fluid (BALF) and serum samples.

Results

A statistically significant increase of TAS and GSH in BALF was observed in lung cancer patients compared to healthy subjects (0.27 ± 0.24 vs. 0.12 ± 0.02 mmol/L, p = 0.02 and 7.56 ± 4.29 vs. 4.62 ± 2.23 μmol/L, p = 0.01 respectively). Statistically significant correlations in cancer patients were observed in BALF between TAS and a. IL-1α (r = 0.87, p < 0.001), b. IL-6 (r = 0.52, p = 0.001) and c. TNF-α (r = 0.67, p < 0.001).

Conclusions

Alteration in antioxidant and inflammatory mediator status was found in lung cancer patients both in serum and in BALF compared to healthy subjects matched for smoking history. Moreover, a positive correlation was observed between antioxidants and pro-inflammatory cytokines, but only locally and not systematically.     

Increased Plasma Levels of Corticosterone and Prolactin and Decreased T3 and T4 Levels in Short-Term Prehepatic Portal Hypertension in Rats

Corticosterone, T₃, T₄, and prolactin serum concentrations at 24 hr (N = 10), 15 days (N = 10), and 45 days (N = 10) of postoperative (postop) evolution were assayed to study the neuroendocrine response to portal hypertension. A triple stenosing ligature of the portal vein was used as the surgical technique of portal hypertension. This technique does not produce mortality and causes a decrease in the serum concentrations of T₃ (0.043 ± 0.009 vs 0.55 ± 0.08 ng/ml) and T₄ (3.93 ± 0.55 vs 4.65 ± 0.67 g/ml) and an increase in those of prolactin (28.61 ± 20.20 vs 12.84 ± 3.96 ng/ml) and corticosterone (397.50 ± 64.17 vs 311.53 ± 57.41 ng/ml) at 45 days postop. The T₃, T₄, prolactin, and corticosterone alterations are associated with a persistent increase of TNF- and NO, whose serum concentrations at 45 days postop are, respectively, 1838.33 ± 247.07 vs 48.89 ± 8.75 pg/ml and 0.43 ± 0.13 vs 0.19 ± 0.01 mmol/ml. TNF- and NO could mediate these hormonal alterations in the evolution of short-term portal hypertension in the rat; thus they are involved in the systemic neuroendocrine response that is induced by this injury.     

Reduced production of immunoreactive interleukin-1 by peripheral blood monocytes of patients with acute and chronic viral hepatitis

The in vitro production of interleukin-1 by peripheral blood monocytes derived from patients with various liver diseases was studied. An impaired production of immunoreactive interleukin-1 (IL-1) (mean±sem) by monocytes stimulated, with an optimal dose (100 ng/ml) of lipopolysaccharide was observed in patients with chronic hepatitis B (N= 13; 32±6 pg/ml) or chronic hepatitis C (N= 13; 61±12pg/ml) as compared to those of healthy control individuals (N=35; 166±24 pg/ml;P=0.0003 andP=0.015, respectively), whereas an unaltered, IL-1 production was seen in patients with alcoholic cirrhosis (N=23; 125±28 pg/ml) and primary biliary cirrhosis (N=6; 111±33pg/ml) Similar to the situation seen in chronic viral hepatitis, lipopolysaccharide-stimulated monocytes from patients with acute hepatitis also showed a decreased IL-1 production in the first week after onset of jaundice (N=17; 55±20 pg/ml;P=0.001) and a return to normal in the second and third week. An impaired production of IL-1 in chronic as well as acute viral hepatitis is a further example of the known disturbed immunoregulation in this disease.     

Studies of phagocytic and killing activities of alveolar macrophages in patients with sarcoidosis

Phagocytosis and killing activities of alveolar macrophages were compared in 17 patients with stage 1 sarcoidosis and 6 healthy controls. The average total cell count of bronchoalveolar lavage fluid from patients with sarcoidosis was 7.8 ± 7.5 × 10⁶ cells; 70.4 ± 15% of these cells were alveolar macrophages and 25.9 ± 16.2% lymphocytes. Average total cell count from controls was 8.33 ± 8.6 × 10⁶ cells, with 92.7 ± 5.9% alveolar macrophages and 6.6 ± 4.4% lymphocytes. Purified alveolar macrophages were tested in in vitro antibacterial assays using S. aureus as a test microbe. Moderate decreases in the kinetics of staphylococcal ingestion were detected in the sarcoidosis group. The intracellular killing activity of macrophages was much lower in the patients with sarcoid than in control subjects. In a pilot study, intracellular killing activity of macrophages from 1 patient: with sarcoidosis was greatly enhanced by 24 hr treatment with transfer factor. In summary, alveolar macrophages from patients with radiographic stage 1 sarcoidosis have decreased bacterial ingestion and intracellular killing activities. These results suggest that macrophages undergo complex functional changes in sarcoidosis that may influence both disease development and host defenses. Offprint requests to: P. Orosi     

Impact of left atrial volume in prediction of outcome after cardiac resynchronization therapy

Left atrial volume index (LAVI) as a predictor of mortality has not been well investigated in patients with cardiac resynchronization therapy (CRT). The purpose of this study is to evaluate the impact of LAVI in predicting mortality in CRT patients.

Methods

We studied 100 consecutive patients who received CRT (male 73, age 69.9 ± 9.6 years). The follow-up duration of all echocardiographic measurements was 14.4 ± 10.5 months after CRT. LAVI was measured from apical views on two-dimensional echocardiography by bi-plane rule. A decrease of left ventricular end systolic volume ≥ 15% after CRT was defined as a positive response to CRT.

Results

The mean LAVI at baseline was 59.9 ± 22.7 ml/m². LAVI in patients who died (78.2 ± 27.5 ml/m²) was significantly greater than those who survived (55.9 ± 19.5 ml/m², p < 0.0001) during follow-up of 17 ± 10.6 months. The area under ROC curve (AUC) for LAVI predicting death was 0.77 (p = 0.0001). The cutoff point for LAVI predicting death was LAVI > 59.4 ml/m². LAVI > 59.4 ml/m² was related to mortality by Cox proportional univariate regression [hazard ratio (HR) = 5.15, 95% CI = 1.48-17.93, p = 0.01]. After adjustment for the variables with significant difference by univariate regression, LAVI > 59.4 ml/m² was continuously related to mortality by multivariate regression (HR = 4.56, 95% CI, 1.30-15.97, p = 0.02). LAVI > 59.4 ml/m² was associated with a near 5-fold increase in mortality during follow-up of 17 ± 10.6 months.

Conclusion

Patients who have LAVI > 59.4 ml/m² continue to have increased mortality despite CRT.     

Clinical Outcomes and Improved Survival in Patients With Protein-Losing Enteropathy After the Fontan Operation

Background

Patients with protein-losing enteropathy (PLE) following the Fontan operation have a reported 50% mortality at 5 years after diagnosis.

Objectives

The aim of this study was to review outcomes in patients with PLE following the Fontan operation.

Methods

From 1992 to 2010, 42 patients (55% male) with PLE following the Fontan operation were identified from clinical databases at the Mayo Clinic. Data were collected retrospectively.

Results

Mean age at PLE diagnosis was 18.9 ± 11.0 years. Initial Fontan operation was performed at 10.1 ± 10.8 years of age. Mean time from Fontan operation to PLE diagnosis was 8.4 ± 14.2 years. Survival was 88% at 5 years. Decreased survival was seen in patients with high Fontan pressure (mean >15 mm Hg; p = 0.04), decreased ventricular function (ejection fraction <55%; p = 0.03), and New York Heart Association functional class >2 at diagnosis (p = 0.04). Patients who died had higher pulmonary vascular resistance (3.8 ± 1.6 Wood units [WU] vs. 2.1 ± 1.1 WU; p = 0.017), lower cardiac index (1.6 ± 0.4 l/min/m² vs. 2.7 ± 0.7 l/min/m²; p < 0.0001), and lower mixed venous saturation (53% vs. 66%; p = 0.01), compared with survivors. Factors were assessed at the time of PLE diagnosis. Treatments used more frequently in survivors with PLE included spironolactone (21 [68%]), octreotide (7 [21%]), sildenafil (6 [19%]), fenestration creation (15 [48%]), and relief of Fontan obstruction (7 [23%]).

Conclusions

PLE remains difficult to treat; however, in the current era, survival has improved with advances in treatment. Further study is needed to better understand the mechanism of disease and ideal treatment strategy.     

Soluble intercellular adhesion molecule-1 (sICAM-1) in patients with systemic lupus erythematosus

Summary Circulating sICAM-1 is known to be elevated in various inflammatory disorders. It is further suggested that elevated levels correlate well with disease activity in several autoimmune disorders. The objectives of this study are to determine the serum sICAM-1 levels in patients with systemic lupus erythematosus (SLE) and correlate sICAM-1 levels with clinical and laboratory (ESR, CRP, anti-dsDNA) measures of disease activity. Forty-one patients (34 female, 7 male) all fulfilling 1982 ARA classification criteria for SLE and 16 healthy controls (8 female, 8 male) were included in the study. Disease activity was measured according to SLEDAI. sICAM-1 was determined by ELISA. Mean sICAM-1 in SLE patients (339±161 ng/ml) were significantly higher than in the controls (216±85 ng/ml) (p<0.005). Although slightly elevated in active patients, there was no statistically significant difference between mean sICAM-1 levels of active and inactive SLE patients (349±183 ng/ml and 316±103 ng/ml respectively) (p>0.05). We could not find a correlation between sICAM-1 levels and any organ involvements. Similarly, no significant correlation was found between ESR, CRP, anti-ds-DNA and sICAM-1. These results suggest that although higher than normal, sICAM-1 levels in SLE do not provide additional information over conventional activity markers.     

Release of interleukin-1 by alveolar macrophages of patients with active pulmonary sarcoidosis

Activated T-lymphocytes play a central role in the alveolitis of pulmonary sarcoidosis by recruiting monocytes, the building blocks of granulomata, to the alveolar structures. The present study suggests that the lung mononuclear phagocyte population, which is derived from blood monocytes, may play a critical role in the pathogenesis of sarcoidosis by modulating local T-cell activation. In this regard, alveolar macrophages from sarcoid patients with high-intensity alveolitis released significantly greater amounts of lymphocyte-activating factor (interleukin-1), in vitro, than did macrophages from sarcoid patients with low-intensity alveolitis, patients with idiopathic pulmonary fibrosis, or normal control subjects (p less than 0.001, each comparison). Consistent with the concept that the lungs of sarcoid patients with low-intensity alveolitis may have a low level of inflammation present, alveolar macrophages from this group released more interleukin-1 than did macrophages from the normal group (p less than 0.05). These observations suggest that in pulmonary sarcoidosis: (1) mononuclear phagocytes are activated, and this state of activation correlates with the activity of the lung disease; (2) activated lung mononuclear phagocytes may modulate lung lymphocyte function, and thus play a critical role in the pathogenesis of this disease.     

Daily production and metabolic clearance of growth hormone in juvenile diabetes mellitus

Summary Daily production (PR) of human growth hormone (HGH) was calculated in patients with juvenile diabetes and control subjects by determining metabolic clearance rate (MCR) of¹³¹I HGH, at equilibrium, and mean endogenous HGH levels throughout a 24 h day. Half hourly sampling or a constant withdrawal pump were used to obtain an integrated mean endogenous HGH level. MCR (liters/day) was significantly reduced in all diabetic subjects both in absolute terms (96 ± 15 vs 274 ± 37) and relative to surface area (62 ± 8 vs 171 ± 21) (p < 0.01). Mean HGH levels were 8.4 ng/ml in the diabetics and 5.5 ng/ml in age matched controls. Daily HGH PR in the diabetic subjects (339 to 1365 g/day) did not exceed values in the control subjects (1005–1426 g/day). The results indicate that the elevated plasma HGH levels and increased HGH response to stimuli observed in diabetes, reflect reduced metabolic clearance, rather than increased pituitary secretion.     

Eosinophilic granulocytes and interleukin-6 level in bronchoalveolar lavage fluid are associated with the development of obliterative bronchiolitis after lung transplantation

In a prospective cohort study, we assessed whether changes in total cell counts and differentiation and interleukin-6 (IL-6), IL-8, and monocyte chemoattractant protein-1 (MCP-1) concentrations in bronchoalveolar lavage fluid (BALF) are associated with a higher risk to develop obliterative bronchiolitis (OB). We investigated 60 lung transplant patients (follow-up of 2 to 8 yr) with either histologic evidence of OB within 1 yr after lung transplantation (n = 19) or no pathology, good outcome (GO) for at least 24 mo and well-preserved lung function, i.e., FEV > or = 80% of baseline (n = 41). Median time between lung transplantation and the first BAL was 42 d for the GO group and 41 d for the OB group (p > 0.05). In the bronchial fraction, median total cell counts (0.06 x 10(3)/ml versus 0.04 x 10(3)/ml), lymphocyte (9 x 10(3)/ml versus 2 x 10(3)/ml), and eosinophilic granulocyte counts (1 x 10(3)/ml versus 0) were significantly higher in the OB group than in the GO group (p < 0.05). In the alveolar fraction, this was the case for the median value of neutrophilic granulocyte counts (19 x 10(3)/ml versus 4 x 10(3)/ml), respectively. Median values of IL-6 and IL-8 concentrations in both bronchial (IL-6: 23 versus 6 pg/ml, IL-8: 744 versus 102 pg/ml) and alveolar fractions (IL-6: 13 versus 3 pg/ml, IL-8: 110 versus 30 pg/ml) of the BALF were significantly higher in the OB group than in the GO group. By means of logistic regression, we showed that higher total cell, neutrophilic granulocyte, and lymphocyte counts, the presence of eosinophilic granulocytes, and higher concentrations of IL-6 and IL-8 were significantly associated with an increased risk to develop OB. We conclude that monitoring cell counts, neutrophilic and eosinophilic granulocytes, IL-6, and IL-8 in BALF within 2 mo after lung transplantation in addition to the transbronchial lung biopsy (TBB) pathology will contribute to a better identification and management of the group of patients at risk for developing OB within a year.     

Evaluation of phagocytes in atopic dermatitis

BackgroundPatients with atopic dermatitis frequently present recurrent infections by pyogenic bacteria or by intracellular microorganisms, suggesting an immune disorder.ObjectiveLaboratorial investigation of phagocyte activity and chemotactic response by neutrophilic polymorphonuclear and mononuclear phagocytes in the peripheral blood of patients with atopic dermatitis from moderate to severe.MethodsThrough a transversal study, patients with atopic dermatitis from moderate to severe were selected. The neutrophilic and mononuclear phagocytes were separated and the phagocytic ingestion of zymosan particles was analysed, in addition to migration distance to the bacterial lipopolysaccharide chemotactic factor, comparing the results to the values obtained from healthy individuals within the same age group.ResultsNineteen patients were selected, 11 female and 8 male. The mean age was 6.47 years (±4.65). Among the 19 patients studied, 14 (73.68%) presented a reduction in the neutrophilic and mononuclear phagocyte activity, with two (1.53%) patients presenting a reduction in the activity of both phagocytes.ConclusionOur results demonstrated a reduction in chemotactic response and phagocytic activity by neutrophilic and/or mononuclear phagocytes in the majority of patients with atopic dermatitis from moderate to severe. Our results were coherent with the clinical data concerning the higher incidence of infections by pyogenic bacteria and fungi in patients with atopic dermatitis, which are microorganisms that require defence by the phagocytes researched in the present study.     

Counterregulation in Type 2 (non-insulin-dependent) diabetes mellitus. Normal endocrine and glycaemic responses,up to ten years after diagnosis

Summary We have examined hormonal and metabolic responses to insulin-induced hypoglycaemia in 10 Type 2 (non-insulin-dependent) diabetic patients treated with tablets and 10 age, sex and weight matched control subjects. Diabetic patients were under 110% ideal body weight, had no autonomie neuropathy and were well controlled (HbA₁, 7.1±0.2%). After the diabetic patients were kept euglycaemic by an overnight insulin infusion, hypoglycaemia was induced in both groups by intravenous insulin at 30 mU·m^–2·min^–1 for 60 min and counterregulatory responses measured for 150 min. There were no significant differences between diabetic patients and control subjects in the rate of fall (3.3±0.3 vs 4.0±0.3 mmol·1^–1·h^–1), nadir (2.4±0.2 vs 2.3±0.1 mmol/l) and rate of recovery (0.027±0.002 vs 0.030±0.003 mmol·1^–1·min^–1) of blood glucose. Increments of glucagon (60.5±5.7 vs 70±9.2 ng/l) and adrenaline (1.22±0.31 vs 1.45±0.31 nmol/l) were similar in both groups. When tested using this model, patients with Type 2 diabetes, without microvascular complications and taking oral hypoglycaemic agents show no impairment of the endocrine response and blood glucose recovery following hypoglycaemia.