Serum mucin antigen (CASA) as a marker of amiodarone-induced pulmonary toxicity.
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Amiodarone is used to treat life-threatening cardiac arrhythmias. Amiodarone-induced pulmonary toxicity (APT) can be difficult to diagnose. APT may result in increased mucus production and mucin expression. Thus, serum mucin-1 was evaluated as a marker for amiodarone-induced pulmonary toxicity. Concentrations of mucin-1 in peripheral blood were determined using cancer-associated serum antigen (CASA) assay in patients taking amiodarone. Eight of ten patients who developed major amiodarone toxicity had high serum CASA levels. Patients with toxicity had a significantly higher mean rank CASA concentration compared with those without major toxicity. CASA shows potential as a marker for amiodarone-induced toxicity, particularly pulmonary toxicity. (+info)
Elimination of cholesterol as cholestenoic acid in human lung by sterol 27-hydroxylase: evidence that most of this steroid in the circulation is of pulmonary origin.
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Human alveolar macrophages have exceptionally high capacity to convert cholesterol into 27-hydroxycholesterol and cholestenoic acid by the sterol 27-hydroxylase mechanism. It is shown here that the human lung has a higher content of 27-hydroxycholesterol relative to cholesterol than any other organ. In order to evaluate the importance of the sterol 27-hydroxylase mechanism for cholesterol homeostasis in the lung, the production of cholestenoic acid by human lung was investigated. Removal of one lung reduced the level of cholestenoic acid in the circulation by 48 +/- 4% (P < 0.005). The levels of cholestenoic acid in the pulmonary artery and in the pulmonary vein showed significant differences (P < 0.002) with higher levels in the pulmonary vein (108 +/- 16 and 104 +/- 16 ng/mL, respectively). This corresponds to a net flux of cholestenoic acid from the lung of about 14 mg/day, which is more than 80% of the reported removal of this oxysterol and its metabolites from the circulation by the liver per day. Bypassing the lung for 60 min led to a reduction in circulating cholestenoic acid (30%) that fits with a pulmonary origin when taking into account the half-life of cholestenoic acid. The level of circulating cholestenoic acid was found to be less in patients with different lung diseases. It is evident that most of the cholestenoic acid in the circulation is of pulmonary origin. The present results suggest that the sterol 27-hydroxylase in the lung is responsible for at least half of the total flux of 27-oxygenated cholesterol metabolites to the liver and that this enzyme system may be of importance for cholesterol homeostasis in the lung. (+info)
The effect of passive smoking on pulmonary function during childhood.
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Passive smoking, especially of maternal origin, is known to influence adversely the development of children's pulmonary function. In this study, the effect of parental smoking on the pulmonary function of 360 primary school children aged 9-13 (mean 10.8 +/- 0.7) years was investigated. Information on parental smoking history was collected using a questionnaire, and spirometric measurements were performed on the children. All spirometric indices were lower in children who had been passively exposed to parental tobacco smoke than those not exposed. The percentage of households in which at least one parent smoked was 81.5%. This figure was significantly lower for mothers (27.5%) than for fathers (79%). Paternal smoking was associated with reduced levels of forced expiratory flow between 25-75% of vital capacity, peak expiratory flow, and flow rates after 50% and 75% of vital capacity expired (p < 0.05). Maternal smoking did not have statistically significant adverse effects on children's pulmonary function. This result might be due to the low occurrence of either pre- or post-natal smoking among mothers and confirms that, in our population, the main target group for antitobacco campaigns should be fathers. (+info)
The safety and usefulness of routine bronchoscopy before stem cell transplantation and during neutropenia.
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Fibreoptic bronchoscopy with bronchoalveolar lavage (BAL) is used for clinical investigation and research into pulmonary complications of stem cell transplantation. Adverse effects of BAL are common in neutropenic patients with lung disease; there are few data on its safety when used routinely in transplant recipients without lung impairment. We describe the complications and usefulness for infection surveillance of routine BAL pre-transplantation and during neutropenia. Thirty-three patients before autologous or allogeneic BMT or PBSCT (B1) and 24 during post-transplant neutropenia (B2) underwent BAL; patients with pulmonary disease were excluded. Subjects were monitored for adverse effects, and BAL fluid was examined for pathogens. Complications of B2 were compared with events seen in 35 neutropenic patients who did not undergo BAL (C). Eighteen percent B1 and 33% B2 subjects showed complications of BAL. Fever occurred in 12% B1 and 26% previously afebrile B2 subjects, compared to 11% of C (P = 0.3). Epistaxis occurred in one B2 subject and two C. Potentially pathogenic organisms were isolated from 18% B1 and 13% B2 BAL fluids; none caused later respiratory infection. Bronchoscopy and BAL pre- and post-transplant had acceptable safety for a research procedure, but were not clinically helpful for infection surveillance. (+info)
Respiratory syncytial virus G and/or SH protein alters Th1 cytokines, natural killer cells, and neutrophils responding to pulmonary infection in BALB/c mice.
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BALB/c mice sensitized to vaccinia virus expressed G protein of respiratory syncytial virus (RSV) develop a Th2-type cytokine response and pulmonary eosinophilia when challenged with live RSV. In this study, BALB/c mice were immunized or challenged with an RSV mutant lacking the G and SH proteins or with DNA vaccines coding for RSV G or F protein. F or G protein DNA vaccines were capable of sensitizing for pulmonary eosinophilia. The absence of the G and/or SH protein in the infecting virus resulted in a consistent increase both in pulmonary natural killer cells and in gamma interferon and tumor necrosis factor expression, as well as, with primary infection, a variable increase in neutrophils and CD11b(+) cells. The development of pulmonary eosinophilia in formalin-inactivated RSV-vaccinated mice required the presence of the G and/or SH protein in the challenge virus. These data show that G and/or SH protein has a marked impact on the inflammatory and innate immune response to RSV infection. (+info)
Atypical Wegener's granulomatosis with positive cytoplasmic antineutrophil cytoplasmic antibodies, ophthalmologic manifestations, and slowly progressive renal failure without respiratory tract involvement.
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A 68-year-old woman had microscopic hematuria and proteinuria since the age of 50. She also had hearing impairment, arthralgia, retinal embolism, peripheral arterial occlusion of the right foot and chronic renal failure during the course. At the age of 68, she had progressive renal failure and nephrotic syndrome with high titers of serum cytoplasmic antineutrophil cytoplasmic antibodies (c-ANCA). No evidence of respiratory tract involvement was found. Methylprednisolone pulse therapy and low dose cyclophosphamide therapy ameliorated the renal failure and reduced the serum c-ANCA level. She, however, died on July 19, 1998 due to pulmonary fungal and pneumocystis carinii infection. (+info)
Clinical and serological associations with anti-RNA polymerase antibodies in systemic sclerosis.
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There are three classes of RNA polymerase enzyme (RNAPs I, II and III). In systemic sclerosis (SSc), three main groups of anti-RNAP sera have been characterized by radioimmunoprecipitation techniques: anti-RNAP I/III sera, anti-RNAP I/II/III sera, and a group precipitating both RNAP II and topoisomerase I (topo I). Some sera in this third group precipitate the phosphorylated (IIO) form of RNAP II in the absence of the unphosphorylated (IIA) form. Certain other antinuclear antibodies (ANA) have also been detected in anti-RNAP IIO/IIA/topo I and anti-RNAP IIO/topo I sera. In the present study of 155 SSc patients, clinical features of individuals from each of these antibody groups were assessed and compared with those of patients from other autoantibody-defined groups. The anti-RNAP I/II/III antibody specificity was closely associated with the presence of diffuse cutaneous SSc (dc-SSc) (77.8%; cf. remaining group, 12.4%; P < 0.001; relative risk (RR) 6.3). Patients with anti-RNAP I/III antibodies also had an increased incidence of dc-SSc, but this was not significant (42.9%; cf. remainder, 15.7%). Anti-RNAP+ patients had a significantly increased incidence of renal involvement (29.0%, cf. remainder, 11.3%; P < 0.05; RR 2.6), with 40% of anti-RNAP I/II/III patients having renal disease. Meanwhile, the presence of anti-centromere antibodies (ACA) was associated with limited cutaneous SSc (lc-SSc) (100.0%; cf. remainder, 75.3%; P < 0. 005), together with reduced incidences of both renal disease (2.4%, cf. remainder, 22.1%: P < 0.01) and pulmonary fibrosis (21.4%, cf. remainder, 52.3%; P < 0.005; RR 1.9). Anti-topo I antibodies were associated with the presence of pulmonary fibrosis (69.7%; cf. remainder, 32.6%; P < 0.001; RR 2.1). A majority of anti-topo I sera were from lc-SSc patients, regardless of whether anti-topo I antibodies occurred alone (75.0%) or together with anti-RNAP IIO + IIA antibodies (75.0%), and this was similar to the remainder (86. 5%; NS). However, when anti-topo I+ patients were compared with the ACA group, and then with all anti-RNAP I+ patients (37.5% lc-SSc), significant differences were found in the occurrence of dc- versus lc-SSc (P < 0.005 and P < 0.05, respectively). In conclusion, these results confirm that there are three main groups of SSc sera, each characterized by the presence of a mutually exclusive SSc-specific autoantibody (ACA, anti-topo I or anti-RNAP I), and distinguished by patterns of cutaneous involvement and specific clinical features. It appears that, in each of the three groups of SSc patients, distinct pathological processes are occurring, which are responsible for the characteristic symptoms, for the modification of particular autoantigens and, consequently, for the production of particular autoantibodies. Based on these data, together with our previous results, it is further hypothesized that anti-RNAP II antibodies may be produced in the context of two different immune response pathways. (+info)
P-selectin and ICAM-1 mediate endotoxin-induced neutrophil recruitment and injury to the lung and liver.
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The role of leukocyte adhesion molecules in endotoxin-induced organ injury was evaluated by administering intraperitoneal Salmonella enteritidis lipopolysaccharide (LPS) to wild-type (WT) mice, P-selectin-deficient mice, intercellular adhesion molecule (ICAM)-1-deficient mice, and P-selectin-ICAM-1 double-mutant mice. In WT mice, there was a sevenfold increase in the number of neutrophils present in the pulmonary vascular lavage fluid, and there were sevenfold more intracapillary neutrophils by electron-microscopic (EM) morphometry at 4 h after intraperitoneal LPS compared with that in control mice. Extravascular albumin accumulation increased approximately twofold in the lungs and liver of WT mice treated with LPS. In the double-mutant mice, although overall mortality after intraperitoneal LPS was not attenuated, there was a significant delay in mortality in the P-selectin-ICAM-1-deficient mutants compared with that in WT mice after intraperitoneal LPS (P < 0.01). Moreover, compared with LPS-treated WT mice, lung and liver extravascular albumin accumulation was significantly lower in LPS-treated P-selectin-ICAM-1 double-mutant mice. Lung myeloperoxidase activity, normalized per 1,000 circulating neutrophils, increased after endotoxin in WT and P-selectin-deficient mice but not in P-selectin-ICAM-1 double-mutant mice. In addition, lung and liver myeloperoxidase activity per 1,000 circulating neutrophils in endotoxin-treated ICAM-1-deficient mice and P-selectin-ICAM-1 double mutants was significantly lower compared with that in endotoxin-treated WT mice. These data suggest that P-selectin and ICAM-1 significantly contribute to lung and liver injury after systemic endotoxemia. (+info)