Variant eotaxin: Its effects on the asthma phenotype

BACKGROUND: Eotaxin, a CC chemokine expressed in the asthmatic lung, has been associated with impaired lung function. The role of its variant form is unknown. OBJECTIVE: The purpose of this study was to detect the population frequency and effects of a known single-nucleotide polymorphism in the eotaxin gene in which a threonine residue (THR(23)) is substituted for the wild-type alanine (ALA(23)) at the 23rd amino acid at the terminus of the peptide leader sequence. METHODS: We measured eotaxin protein secretion in 293 cells transfected with expression vectors and in PBMCs obtained from individuals bearing the alternative forms of the gene. A case-control study of plasma eotaxin levels and eosinophil counts, a comparison of baseline lung function by genotype in a population of 806 subjects with asthma, and a comparison of the allele frequency with a nonasthmatic population were performed. RESULTS: Human 293 cells and PBMCs with THR(23) variant eotaxin secreted significantly less eotaxin protein than did ALA(23)-bearing cells. In the case-control study, THR(23)-THR(23) individuals had lower plasma levels of eotaxin (310 [240-350] vs 420 [270-700] pg/mL; P < .05) and eosinophil counts (120 [5-220] vs 190 [110-470] cells/microL; P < .05) than ALA(23)-ALA(23) subjects; heterozygous subjects had intermediate levels. Higher levels of lung function were associated with THR(23) eotaxin (percent of predicted FEV(1), 65% +/- 3.5% [THR(23)-THR(23)] vs 58% +/- 0.9% [THR(23)-ALA(23)] and 56% +/- 0.5% [ALA(23)-ALA(23)]; P < .05). CONCLUSION: The THR(23) variant is associated with both decreased eosinophil counts and higher levels of lung function in subjects with asthma.     

Current status of anticoagulant therapy

Anticoagulant therapy has stood the test of time. Full-dose heparin and warfarin prevent recurring pulmonary embolism and deep venous thrombosis. Their use is indicated in patients who have experienced venous thromboembolism unless contraindications are compelling. Low-dose heparin is successful in preventing the initial episode of venous thrombosis in most patients at high risk for the development of thrombophlebitis. Warfarin reduces the incidence of systemic embolization in patients with heart disease and atrial fibrillation and in patients with artificial heart valves. Evidence is accumulating to suggest that warfarin may still retain an important role in the management of patients with myocardial infarction. However, bleeding remains an inevitable risk in patients receiving anticoagulant therapy. The risk, however, can be diminished when both the physician and patient understand the mechanism of action of the drugs and the factors that predispose to bleeding.     

Safety of aerosolized liposomal versus deoxycholate amphotericin B formulations for prevention of invasive fungal infections following lung transplantation: a retrospective study

BACKGROUND: Nebulized amphotericin B deoxycholate (AmBd) has been used to prevent invasive pulmonary aspergillosis after lung transplantation. METHODS: In this retrospective study we compared the safety and tolerability of nebulized AmBd and nebulized liposomal amphotericin B (L-AmB) in 38 consecutive lung transplant recipients. Progress notes, medication administration records, microbiology, and pulmonary function reports were reviewed. Histologic sections from lung tissue were examined. Plasma amphotericin B levels were measured. RESULTS: A total of 1206 doses of AmBd and 1149 doses of L-AmB were administered. Eighteen patients received AmBd only, 11 received L-AmB only, and 9 received the medications sequentially. The total number of complaints vs. the number of doses administered was 1.0% for AmBd-treated patients and 1.2% for L-AmB-treated patients. No differences were observed between the treatment groups on lung biopsy specimens. Plasma amphotericin B levels were <0.2-0.9 microg/mL in AmBd-treated patients and <0.2 microg/mL in L-AmB-treated patients. CONCLUSIONS: In lung transplant recipients, both inhaled AmBd and L-AmB were safe and well tolerated over a large number of medication exposures.     

Sputum eosinophil counts predict asthma control after discontinuation of inhaled corticosteroids

BACKGROUND: Although inhaled corticosteroids (ICSs) are effective in preventing deterioration in asthma control, at least half of subjects with mild-to-moderate asthma will remain stable when these agents are discontinued. OBJECTIVE: We sought to determine whether noninvasive markers of inflammation predict which individuals maintain asthma control after discontinuation of ICSs. METHODS: We analyzed data obtained from 164 subjects with mild-to-moderate asthma who participated in a 16-week trial comparing the effects of continued ICS use with the effects of a switch to salmeterol or placebo. RESULTS: In comparison with continued ICS use, a switch to salmeterol or placebo was associated with increased rates of asthma deterioration over 16 weeks (9.3% vs 24.1% and 37.5%, respectively; P = .04 and P < .001, respectively). We found that neither exhaled nitric oxide nor methacholine PC 20 , when measured at randomization or 2 weeks after randomization, were significant predictors of subsequent asthma control in subjects who discontinued ICSs. However, both induced sputum eosinophil counts measured 2 weeks after a switch from ICS to placebo and changes in sputum eosinophil counts from before cessation of ICSs to after a switch to placebo predicted subsequent asthma deterioration (area under the receiver-operating characteristic curve, 0.771 [ P < .001] and 0.825 [ P < .001], respectively). CONCLUSION: On the basis of a model treatment strategy, we estimate that allocating subjects to ICS therapy on the basis of changes in sputum eosinophil counts after a trial discontinuation could allow 48% of subjects with mild-to-moderate asthma to discontinue ICS therapy without an increased risk of asthma deterioration over a period of at least 14 weeks.     

Psychiatric Morbidity and Depressive Symptomatology in Patients with Permanent Pacemakers

Implantation of a permanent pacemaker requires a psychological effort on the patient's part for adaptation in the acute term, and chronically, it restricts activities of the patient and may cause some psychiatric disturbances. To investigate psychiatric morbidity and depressive symptomatology of the patients with permanent pacemakers, 84 pacemaker patients were diagnosed using the DSM-III-R criteria and depressive symptoms were determined by modified Hamilton Depression Rating Scale (mHDRS). Sixteen (19.1 %) patients had been given a psychiatric diagnosis. The most frequent diagnoses were adjustment disorder (5.9%) and major depressive episode (4.7%). Nine patients (10.7%) were diagnosed as having clinical depression (mHDRS ≥ 17). The mean score of mHDRS was 7.57 ± 7.46, and the severity of depression was significantly higher in females. The most frequent symptoms are difficulties in work and activities (53.6%), psychic anxiety (48.8%), loss of energy (42.9%), and hypochondriasis and insomnia (39.3%). Depressed mood, psychic anxiety, loss of energy, loss of interest, insomnia, and hypochondriasis were significantly more frequent in females. Uneducated patients had a more significant loss of energy than educated patients. Depressed mood, psychic anxiety, and somatic concerns and symptoms were more frequent in patients with permanent pacemakers than in the general population. These symptoms, resembling mixed anxiety-depression disorder, were related to fears of having a permanent pacemaker, since our series were composed of uneducated patients who did not have enough knowledge about the device.