Biomedical subjects

A P Perruchoud

Publications and source records attributed to A P Perruchoud.

At least 19 recordsLinked to original sources

PubMed1999

Calcium channel blockers activate the interleukin-6 gene via the transcription factors NF-IL6 and NF-kappaB in primary human vascular smooth muscle cells.

BACKGROUND: Calcium channel blockers (CCB) of all subclasses: the dihydropyridines, benzothiazepines, and phenylalkylamines, at nanomolar concentrations, have been shown to up-regulate interleukin-6 (IL-6) mRNA. We investigated the underlying molecular mechanism responsible for IL-6 induction in response to the CCB amlodipine, diltiazem, and verapamil in primary human vascular smooth muscle cells (VSMC). METHODS AND RESULTS: All 3 CCB directly activated transcription of the human IL-6 gene in primary human VSMC in a time- and dose-dependent manner, as demonstrated by luciferase reporter gene assays using a 651-bp fragment of the human IL-6 gene promoter. Deletion analysis of the IL-6 promoter revealed that CCB inducible promoter activity was localized to a 160-bp fragment directly upstream of the transcriptional start site of the IL-6 gene. Known transcription factor consensus sequences within this fragment include a NF-IL6 and a NF-kappaB site. Site-directed mutagenesis suggested that both transcription factors had positive regulatory activity and cooperatively transmitted induction of the IL-6 gene by CCB. The data are confirmed by electrophoretic mobility shift analyses using nuclear extracts from CCB-stimulated and control primary VSMC. CCB of all subclasses increased DNA binding of NF-IL6 and NF-kappaB as early as 30 minutes after stimulation with the drugs. This effect was independent of intracellular calcium concentrations because calcium-free medium did not increase NF-IL6 or NF-kappaB activity. CONCLUSIONS: The results demonstrate that CCB of all 3 subclasses are capable of activating NF-IL6 and NF-kappaB. CCB may thus directly regulate cellular functions by affecting the activity of transcription factors independent of changes of intracellular calcium concentrations, an observation that is of interest considering the biological effects induced by CCB.

CCAAT-Enhancer-Binding Proteins↗

PubMed1999

Transforming growth factor-beta1 induces interleukin-6 expression via activating protein-1 consisting of JunD homodimers in primary human lung fibroblasts.

Transforming growth factor (TGF)-beta1 induces extracellular matrix deposition and proliferation of mesenchymal cells. We recently reported that interleukin (IL)-6 is an essential mediator of growth factor-induced proliferation of lung fibroblasts. Here, we demonstrate by reverse transcriptase polymerase chain reaction and enzyme-linked immunoassay that TGF-beta1 is a potent inducer of IL-6 mRNA and protein in primary human lung fibroblasts. Transient transfections of fibroblasts with a luciferase reporter gene construct containing nucleotides -651 to +1 of the human IL-6 promoter revealed that TGF-beta1 also potently activated IL-6 promoter activity. Progressive 5'-deletions and site-directed mutagenesis of the parental construct located the TGF-beta1-responsive cis-regulatory element to a known activating protein-1 (AP-1) sequence (nucleotides -284 to -276). Gel shift analyses revealed that AP-1 DNA binding activity in nuclear extracts was increased 30 min after stimulation with TGF-beta1. In contrast, neither CCAAT enhancer-binding protein-beta, NF-kappaB, nor Sp1 were activated by TGF-beta1. Supershift analyses demonstrated that the AP-1 complex induced by TGF-beta1 was composed of Jun isoforms and absent of Fos isoforms. Moreover, this complex was found to be a JunD homodimer. Our data thus demonstrate that TGF-beta1 is a potent inducer of IL-6 in primary human lung fibroblasts. The TGF-beta1-activated JunD homodimer may be essential for a majority of the biological effects induced by TGF-beta1 in this cell type, such as proliferation and extracellular matrix synthesis.

Base Sequence↗

PubMed1999

[Is self-management practical in bronchial asthma?].

The threat and uncertainty involved in an asthma attack reduce the quality of life for the patient. Life quality can be improved if the patient learns self-management principles. This is easy to learn and involves a simple procedure requiring the patient to refer to written instructions in the event of an asthma exacerbation. As a basis for treatment the patient needs to measure maximum peak flow, which can be done with an easy-to-use peak flow meter. A value above 80% of the personal best indicates that the treatment has been successful. By means of printed instructions in credit card format, the appropriate treatment for particular peak flow values and/or symptoms can be looked up and administered. So far there have been no self-management studies providing a definite answer on what interventions are effective and cost-effective. One clear result is that inhaled steroid therapy must be initiated early. Learning self-management patently leads to improvement in the patient's life quality and safety. In the long run this concept appears to be cost-saving with regard to days lost through sickness and hospitalization.

Anti-Asthmatic Agents↗

PubMed1999

[Etiology, diagnosis and therapy of COPD].

COPD is a disorder characterized by chronic exspiratory airflow limitation in patients with chronic bronchitis and/or emphysema. The obstruction is generally progressive, but may be partially reversible and may be accompanied by airway hyperreactivity. In this review we discuss the epidemiology, Pathophysiology, clinical features, diagnostic approaches and therapeutic management in patients with COPD. Cigarette smoking is the main risk factor for the development and progression of COPD; environmental or occupational exposure to dust or fumes and genetic factors are further contributing factors. Therefore, smoking cessation is the most important therapeutic approach. Better knowledge of neutrophilic inflammation led to the development of new drugs for the treatment of COPD. The new long-acting inhaled beta 2-agonists fundamentally improved antiobstructive therapy. They are useful to control night-time or early morning symptoms. The role of steroids and theophylline is still unclear. Their value and efficient use are discussed.

Administration, Inhalation↗

PubMed1999

Extracellular matrix deposition by primary human lung fibroblasts in response to TGF-beta1 and TGF-beta3.

Increased collagen and extracellular matrix (ECM) deposition within the lung is a characteristic feature of lung fibrosis. Transforming growth factor (TGF)-beta isoforms play a pivotal role in the production of collagen and ECM. In this study, we investigated the effects of TGF-beta1 and TGF-beta3 on the main processes controlling ECM deposition using primary human lung fibroblasts. We analyzed 1) collagen metabolism by [3H]proline incorporation, 2) matrix metalloproteinase (MMP) expression by substrate gel zymography, and 3) tissue inhibitor of metalloproteinases (TIMP) expression by Western blot analysis. TGF-beta1 and TGF-beta3 increased the percentage of secreted collagens in supernatants of primary fibroblasts from 8.0 +/- 1.2 (control) to 23.6 +/- 4.6 and 22.3 +/- 1.3%, respectively. The collagen percentage in deposited ECM was increased from 5.8 +/- 0.3 (control) to 9.0 +/- 0.5 and 8.8 +/- 0.5% by TGF-beta1 and TGF-beta3, respectively. Secretion of MMP-1 (interstitial collagenase) by fibroblasts was reduced by both TGF-beta isoforms, whereas secretion of MMP-2 (gelatinase A) was unaffected by either of the two isoforms. Both TGF-beta isoforms increased TIMP-1 protein expression, whereas TIMP-2 protein was decreased. We thus conclude that TGF-beta1 and TGF-beta3 are equally potent in increasing ECM deposition. Their fibrotic effect in lung fibroblasts results from 1) an increase in the secretion and deposition of total ECM and collagens, 2) a decrease in MMP-1 secretion, and 3) an increase of TIMP-1 expression.

Blotting, Western↗

PubMed1999

Long-term ambient air pollution and respiratory symptoms in adults (SAPALDIA study). The SAPALDIA Team.

The association between long-term exposure to ambient air pollution and respiratory symptoms was investigated in a cross-sectional study in random population samples of adults (aged 18 to 60 yr, n = 9,651) at eight study sites in Switzerland. Information on respiratory symptoms was obtained with an extended version of the European Community Respiratory Health Survey questionnaire. The impact of annual mean concentrations of air pollutants was analyzed separately for never-, former, and current smokers. After controlling for age, body mass index, gender, parental asthma, parental atopy, low education, and foreign citizenship, we found positive associations between annual mean concentrations of NO2, total suspended particulates, and particulates of less than 10 micrometers in aerodynamic diameter (PM10) and reported prevalences of chronic phlegm production, chronic cough or phlegm production, breathlessness at rest during the day, breathlessness during the day or at night, and dyspnea on exertion. We found no associations with wheezing without cold, current asthma, chest tightness, or chronic cough. Among never-smokers, the odds ratio (95% confidence interval) for a 10 micrograms/ m3 increase in the annual mean concentration of PM10 was 1. 35 (1.11 to 1.65) for chronic phlegm production, 1.27 (1.08 to 1.50) for chronic cough or phlegm production, 1.48 (1.23 to 1.78) for breathlessness during the day, 1.33 (1.14 to 1.55) for breathlessness during the day or at night, and 1.32 (1.18 to 1.46) for dyspnea on exertion. No associations were found with annual mean concentrations of O3. Similar associations were also found for former and current smokers, except for chronic phlegm production. The observed associations remained stable when further control was applied for environmental tobacco smoke exposure, past and current occupational exposures, atopy, and early childhood respiratory infections when restricting the analysis to long-term residents and to non- alpine areas, and when excluding subjects with physician-diagnosed asthma. The high correlation between the pollutants makes it difficult to sort out the effect of one single pollutant. This study provides further evidence that long-term exposure to air pollution of rather low levels is associated with higher prevalences of respiratory symptoms in adults.

Adolescent↗

PubMed1999

Prospective evaluation of an algorithm for the functional assessment of lung resection candidates.

Patients with impaired pulmonary function are at increased risk for the development of postoperative complications. Recently exercise testing and predicted postoperative (ppo) function have gained increasing importance in the evaluation of lung resection candidates. We prospectively evaluated an algorithm for the preoperative functional evaluation that was developed at our institution. This algorithm incorporated the cardiac history including an electrocardiogram (ECG), and the three parameters FEV1, diffusing capacity of the lungs for carbon monoxide (DLCO), and maximal oxygen uptake (VO2max), as well as their respective ppo values (FEV1-ppo, DLCO-ppo, and VO2max-ppo) calculated based on radionuclide perfusion scans. A consecutive group of 137 patients (mean age 62 yr; range 23 to 81; 102 males, 35 females) with clinically resectable lesions underwent assessment according to our algorithm. Five patients were deemed functionally inoperable, 132 passed the algorithm and underwent pulmonary resections with standard thoracotomy: 9 segmental or wedge resections, 85 lobectomies (inclusive 3 bilobectomies), and 38 pneumonectomies. All patients were extubated within 24 h. The mean stay in the ICU was 1.4 (+/- 1.8) d, and the mean hospital stay was 14.6 (+/- 5) d. Postoperative complications (within 30 d) occurred in 15 patients (11%), of whom two died (overall mortality rate 1.5%). In comparison to our previous series this meant a 50% reduction in complications whereas the percentage of inoperable patients remained unchanged (4% now, 5% before). We conclude that adherence to our algorithm resulted in a very low complication rate (morbidity and mortality), and excluded more rigorous patient selection as a bias for the improved results.

Aged↗

PubMed1999

Peak flow variability in the SAPALDIA study and its validity in screening for asthma-related conditions. The SPALDIA Team.

We used 3-wk peak expiratory flow (PEF) measurements (twice daily) made in the diary study of the population-based Swiss Study on Air Pollution and Lung Disease in Adults to describe PEF-variability (PEF(var)) (amplitude as a percent of the mean, PEF [i.e., difference between morning and evening values divided by the mean]) in the study population and in five subgroups (physician-diagnosed asthma; current asthma, or physician-diagnosed asthma plus asthma attacks and/or medication; history of wheezing without a cold; hyperreactive; and nonsymptomatic). We assessed the performance of PEF(var) as a potential tool with which to screen for asthma. Alternatively, subjects with a PEF(var) of >/= 20%, >/= 30%, and >/= 50% on at least 2 d were considered to have high variability. The analyses were conducted for subgroups with different pretest probabilities for asthma-related conditions. The median PEF(var) was 4.5%. Among asthmatic subjects, women had nonsignificantly higher PEF(var) values than did men. In all other groups, women had significantly lower PEF(var). Both in the entire population and in subgroups with a higher pretest probability for asthma-related conditions, screening performance of PEF was limited. A PEF(var) of >/= 20% on at least 2 d detected current asthma with a sensitivity of 36% (specificity = 90%; positive predictive value = 16.4%). Results were better among subjects with a history of wheezing without colds (sensitivity = 40.4%; specificity = 83.6%; positive predictive value = 45.2%). PEF(var), a useful measure both clinically and in epidemiology, is of limited value when unselected populations are screened for asthma-related conditions, since the overlap of PEF(var) distributions across subgroups is large.

Adolescent↗

PubMed1999

Evaluation of a new self-expandable silicone stent in an experimental tracheal stenosis.

STUDY OBJECTIVES: To assess the usefulness of an animal model for testing new tracheobronchial stents. SETTING: Animal laboratory of a university hospital. ANIMALS AND INTERVENTIONS: In a series with 12 mini-pigs, we induced a stable fibromalacic tracheal stenosis that was 50% to 70% of the normal tracheal diameter. After dilation we inserted a 16 x 40-mm self-expandable silicone stent into the stenotic part of the trachea in 10 of the mini-pigs. Five of the stents had a smooth outer surface, and five had additional silicone retaining spikes. Because of a long stenosis in two of the mini-pigs, two overlapping stents (one smooth and one with spikes) were inserted. MEASUREMENTS AND RESULTS: Stent deployment was successful and resulted in the disappearance of the slight to moderate stridor in all of the mini-pigs. Over a mean (+/- SD) observation period of 24 days (range, 10 to 41 days), all of the mini-pigs redeveloped stridor. Three of them died unexpectedly of suffocation: in all three a smooth stent had migrated, leading to total obstruction of the stenosis. In total, five of the six smooth stents migrated, and only one of the six spiked stents migrated. There was considerable granulation tissue formation at the ends of all of the stents. In the two control mini-pigs, a 12 x 35-mm Dumon stent was inserted. Both Dumon stents migrated, and one of them had considerable granuloma formation at its ends. At the end of the observation period, all stents were removed endoscopically and were found not to have deteriorated over time. CONCLUSIONS: Our model proved to be suitable for the evaluation of the technical aspects of the Polyflex stent. Spikes on the outer stent surface are more effective in preventing migration than smooth-surface stents. Long-term compatibility, however, seems to be difficult to test with our model because both the Polyflex and the Dumon stents had excessive granulation tissue formation at both ends, a factor which--in the case of the Dumon stent--does not occur to such a degree in benign human airway stenoses. Our results indicate a need for prospective long-term studies in benign human airway stenoses.

Animals↗

PubMed1998

[Dealing with errors in medicine].

Iatrogenic disease is probably more commonly than assumed the consequence of errors and mistakes committed by physicians and other medical personnel. Traditionally, strategies to prevent errors in medicine focus on inspection and rely on the professional ethos of health care personnel. The increasingly complex nature of medical practise and the multitude of interventions that each patient receives increases the likelihood of error. More efficient approaches to deal with errors have been developed. The methods include routine identification of errors (critical incidence report), systematic monitoring of multiple-step processes in medical practice, system analysis, and system redesign. A search for underlying causes of errors (rather than distal causes) will enable organizations to collectively learn without denying the inevitable occurrence of human error. Errors and mistakes may become precious chances to increase the quality of medical care.

Cross-Cultural Comparison↗

PubMed1998

A phase I study of adenovirus-mediated wild-type p53 gene transfer in patients with advanced non-small cell lung cancer.

Mutations of the tumor suppressor gene p53 are the most common genetic alterations observed in human cancer. Loss of wild-type p53 function impairs cell cycle arrest as well as repair mechanisms involved in response to DNA damage. Further, apoptotic pathways as induced by radio- or chemotherapy are also abrogated. Gene transfer of wild-type p53 was shown to reverse these deficiencies and to induce apoptosis in vitro and in preclinical in vivo tumor models. A phase I dose escalation study of a single intratumoral injection of a replication-defective adenoviral expression vector encoding wild-type p53 was carried out in patients with incurable non-small cell lung cancer. All patients enrolled had p53 protein overexpression as a marker of mutant p53 status in pretreatment tumor biopsies. Treatment was performed either by bronchoscopic intratumoral injection or by CT-guided percutaneous intratumoral injection of the vector solution. Fifteen patients were enrolled in two centers, and were treated at four different dose levels ranging from 10(7) to 10(10) PFU (7.5 x 10(9) to 7.5 x 10(12) particles). No clinically significant toxicity was observed. Successful transfer of wild-type p53 was achieved only with higher vector doses. Vector-specific wild-type p53 RNA sequences could be demonstrated in posttreatment biopsies of six patients. Transient local disease control by a single intratumoral injection of the vector solution was observed in four of those six successfully transduced patients. There was no evidence of clinical responses at untreated tumor sites. Wild-type p53 gene therapy by intratumoral injection of a replication-defective adenoviral expression vector is safe, feasible, and biologically effective in patients with advanced non-small cell lung cancer.

Adenoviridae↗

PubMed1998

[Chylothorax as the initial manifestation of malignant Hodgkin lymphoma].

A 22 year-old man complaining of slight thoracic pain, was found to have a right pleural effusion in his chest X-ray. The pleural aspiration yielded chylous fluid and radiological examination and biopsy of a mediastinal mass led to the diagnosis of Hodgkin's disease of the nodular sclerosis type with supra- and radiologically infradiaphragmatic disease and a pathological fracture of the sternum. After complete initial aspiration of the pleural effusion the chylothorax did not recur following initiation of a combination chemotherapy, and a clear regression of the lymphoma was found after the first 3 cycles. This case provides an example of an oligosymptomatic, right sided chylothorax as the first manifestation of Hodgkin's disease in a young immuno-competent patient.

Adult↗

PubMed1998

[Swiss Study on Air Pollution and Lung Diseases in Adults (SAPALDIA)].

Long-term health effects of moderate ambient air pollution are rarely investigated. In Switzerland, no large-scale study has addressed this issue so far. Important results of the Swiss Study on Air Pollution and Lung Disease in Adults (SAPALDIA) are presented. During the period 1991-1993, SAPALDIA investigated a random population sample (18-60 years) in eight Swiss areas with different environmental characteristics (Aarau, Basel, Davos, Geneva, Lugano, Montana, Payerne, Wald). In total, 9651 adults (60%) participated in the cross-sectional investigation (part 1, 1991), consisting of the following standardized procedures: questionnaire (interview), forced expiratory lung function test, bronchial challenge with methacholine, atopy assessment (Phadiatop, unspecific total IgE), allergy skin tests, and endexpiratory CO-measurements. Subjects with a history of respiratory symptoms, increased bronchial reactivity, reduced lung function (FEV1/FVC < 80% predicted) and 150 healthy never-smokers were included in the subsequent diary study (part 2; n = 3281, 1992/93). Peak flow (morning and evening), symptoms, medication, personal activity and visits to the doctor were monitored. Across regions, annual mean values ranged from 9 to 52 mg/m3 (NO2) and 10 to 33 mg/m3 (PM10) respectively. Air pollution had effects on prevalence of dyspnea (+41% per 10 mg/m3 increment of the annual mean PM10, 95% CI 20-65%), on symptoms of chronic bronchitis (+31%, 10-55%), on FVC (-3.1%; -3.7 to -2.6%), and FEV1 (-1.1%; -1.7% to -0.5%), on the incidence of respiratory symptoms and the length of symptomfree intervals (11% change per 10 mg/m3 PM10), but not on the prevalence of asthma. Environmental tobacco smoke (ETS) showed impact on wheezing (OR 1.94; 1.39-2.70), asthma (1.39; 1.04-1.86), bronchitis (1.60; 1.24-2.08) and chronic bronchitis (1.50; 1.11-2.02). Health effects of moderate air pollution were confirmed in Switzerland. Although for the individual the relative risks are small, the public health impact may be considerable. An ongoing follow-up will investigate the mortality profile of the SAPALDIA cohort.

Adolescent↗

PubMed1998

Corticosteroids inhibit the expression of the vascular endothelial growth factor gene in human vascular smooth muscle cells.

The vascular endothelial growth factor (VEGF) is a specific mitogen for vascular endothelial cells and enhances vascular permeability and edemagenesis. VEGF is also a major regulator of angiogenesis and may be a key target for inhibiting angiogenesis in angiogenesis-associated diseases. Among the extensively studied angiostatic compounds are several corticosteroids when used alone or in combination with heparin. In this study we present evidence for an additional mechanism of action of hydrocortisone, cortisone and dexamethasone in inhibiting edemagenesis or angiogenesis. In cultures of aortic human vascular smooth muscle cells these corticosteroids (1 x 10(-8) to 1 x 10(-12) M) abolished the platelet-derived growth factor-induced (PDGF) expression of the VEGF gene in a dose-dependent manner. In contrast, two precursors of corticosteroids, desoxycorticosterone or pregnenolone, did not affect PDGF-induced VEGF expression. Our findings indicate that the capacity of corticosteroids to reduce edema or to prevent new blood vessel formation may be attributed, at least in part to the ability of these agents to abolish the expression of VEGF.

Anti-Inflammatory Agents↗

PubMed1998

Compartmentalization of pro-inflammatory cytokines in tuberculous pleurisy.

Increased levels of interleukin-6 (IL-6) and IL-8 are found in various immunologically mediated inflammatory disorders. Concentrations of IL-6, IL-8 and the soluble form of the IL-6 receptor (sIL-6R) were determined in serum and effusion fluid of 25 patients with tuberculous pleurisy utilizing enzyme linked immunosorbent assays (EIA). Serum IL-6 levels were only slightly increased in patients with tuberculous pleurisy in comparison to controls (11.1 +/- 2.1 vs 7.3 +/- 1.0 pg ml-1). IL-8 could not be detected in the serum of tuberculosis patients, but it was detected in the serum of healthy controls (8.0 +/- 1.5 pg ml-1). In comparison to serum, IL-6 and IL-8 were found in high concentrations in pleural effusions (IL-6: 932 +/- 70 vs 11.1 +/- 2.1 pg ml-1, P < 0.0001; IL-8: 450 +/- 85 vs 0 +/- 0 pg ml-1). In contrast, sIL-6R concentrations were much higher in serum compared to pleural effusion levels [30,477 +/- 1905 vs 9881 +/- 1177 pg ml-1, P < 0.0001 (mean +/- SEM)]. The authors conclude that elevated levels of IL-6 and IL-8 in pleural effusions are compartmentalized at the site of active disease. The low levels of sIL-6R in the presence of high levels of IL-6 in pleural effusions, and the high levels of sIL-6R in the presence of low levels of IL-6 in serum suggest that the expression or shedding of sIL-6R may be downregulated in the presence of excessive amounts of IL-6.

Adult↗

PubMed1998

A 340 kDa hyaluronic acid secreted by human vascular smooth muscle cells regulates their proliferation and migration.

The formation of atherosclerotic lesions is characterized by invasion of vascular smooth muscle cells (VSMC) into the tunica intima of the arterial wall and subsequently by increased proliferation of VSMC, a process apparently restricted to the intimal layer of blood vessels. Both events are preceded by the pathological overexpression of several growth factors, such as platelet-derived growth factor (PDGF) which is a potent mitogen for VSMC and can induce their chemotaxis. PDGF is generally not expressed in the normal artery but it is upregulated in atherosclerotic lesions. We have previously shown that PDGF-BB specifically stimulates proliferating VSMC to secrete a 340 kDa hyaluronic acid (HA-340). Here, we present evidence regarding the biological functions of this glycan. We observed that HA-340 inhibited the PDGF-induced proliferation of human VSMC in a dose-dependent manner and enhanced the PDGF-dependent invasion of VSMC through a basement membrane barrier. These effects were abolished following treatment of HA-340 with hyaluronidase. The effect of HA-340 on the PDGF-dependent invasion of VSMC coincided with increased secretion of the 72-kDa type IV collagenase by VSMC and was completely blocked by GM6001, a hydroxamic acid inhibitor of matrix metalloproteinases. HA-340 did not exert any chemotactic potency, nor did it affect chemotaxis of VSMC along a PDGF gradient. In human atheromatic aortas, we found that HA-340 is expressed with a negative concentration gradient from the tunica media to the tunica intima and the atheromatic plaque. Our findings suggest that HA-340 may be linked to the pathogenesis of atherosclerosis, by modulating VSMC proliferation and invasion.

Aorta↗

PubMed1998

Current allergic asthma and rhinitis: diagnostic efficiency of three commonly used atopic markers (IgE, skin prick tests, and Phadiatop). Results from 8329 randomized adults from the SAPALDIA Study. Swiss Study on Air Pollution and Lung Diseases in Adults.

Total serum IgE, Phadiatop, and the skin prick test (SPT) are commonly used to diagnose atopic diseases. However, no large study has ever been done to test their diagnostic efficiency. We studied the diagnostic value of these three atopic markers in 8329 well-randomized adults from the Swiss Population Registry. The prevalence of current allergic asthma (CAA) was 1.8% and of current allergic rhinitis (CAR) 16.3%. The prevalences of positive Phadiatop, positive SPT (at least, one out of eight SPT to common aeroallergens with a wheal of > or = 3 mm), and positive total IgE (IgE > or = 100 kU/l) were 29, 23, and 23%, respectively. To diagnose CAA and CAR, the sensitivity of Phadiatop was significantly higher than that of SPT (72.5% vs 65.4%, 77.1% vs 68.4% respectively; P < 0.01 and < 0.001) and IgE (72.5% vs 56.9%, 77.1% vs 43.9%, respectively; both P < 0.001). The sensitivity of SPT was significantly higher (68.4% vs 43.9% P < 0.001) than that of IgE to diagnose CAR. When CAA and CAR were excluded, the SPT specificity was significantly higher than that of Phadiatop (77.8% vs 71.9% and 85.9% vs 80.5%, respectively; both P < 0.001): when CAR was excluded, SPT was significantly higher than IgE (85.9 vs 81.4%; P < 0.001). SPT had significantly the best positive predictive value for CAA (5.2% for SPT vs 4.6% for both IgE and Phadiatop; both P < 0.001) and CAR (48.7% for SPT vs 43.5% for Phadiatop and 31.6% for IgE; both P < 0.001). The three markers of atopy had roughly the same negative predictive value (NPV) for CAA, but IgE had a significantly lower NPV for CAR than SPT and Phadiatop (88.1% vs 93.3% and 94.7%, respectively; both P < 0.001). The diagnostic efficiency of SPT was significantly higher than that of Phadiatop (83.1% vs 79.9% and 77.6 vs 71.9%, respectively; both P < 0.001) to diagnose CAR and CAA. IgE and SPT had equal efficiency (77.6%), which was significantly higher than that of Phadiatop, to diagnose CAA (71.9%; both P < 0.001). In conclusion, SPT have the best positive predictive value and the best efficiency to diagnose respiratory atopic diseases. Furthermore, SPT give information on sensitivity to individual allergens and should therefore be used primarily by clinicians to assess respiratory allergic diseases. Moreover, they are cheaper and provide immediate, educational information for both patient and physician.

Adolescent↗

PubMed1998

Proinflammatory cytokine levels in patients with lung cancer and carcinomatous pleurisy.

Increased levels of interleukin-6 (IL-6) and interleukin-8 (IL-8) have been reported in various diseases, including lung cancer. The role of the soluble form of the IL-6 receptor (sIL-6R) remains to be explored. We therefore measured IL-6, IL-8 and sIL-6R in effusion fluid and blood serum of 10 lung cancer patients with carcinomatous pleurisy (5 men, 5 women, age 64.3 +/- 4.4 years) by enzyme-linked immunosorbent assays. Serum levels of healthy individuals served as control. Concentrations of sIL-6R were much higher in serum compared to pleural effusion fluids of tumor patients (25,698 +/- 1,993 vs. 9,438 +/- 1,407 pg/ml: p < 0.0001). In contrast, IL-6 and IL-8 were found at high concentrations in carcinomatous pleural effusions in comparison to serum (IL-6: 964 +/- 176 vs. 10.2 +/- 1.3 pg/ml, p < 0.0001; IL-8: 319 +/- 85 vs. 9.6 +/- 9.6 pg/ml, p < 0.0001). The serum concentrations of IL-6 were not significantly increased in lung cancer patients (10.2 +/- 1.3 pg/ml) in comparison to controls (7.3 +/- 1.0 pg/ml). IL-8 was detected in the serum of only 1 patient and in low levels in the serum of controls (8.0 +/- 1.5 pg/ml; all values are mean +/- SEM). We conclude from this study that decreased levels of sIL-6R, but increased levels of IL-6 and IL-8, are found in pleural effusion fluid of patients with lung cancer and carcinomatous pleurisy. The low sIL-6R levels in the presence of high IL-6 levels in pleural effusions and the high sIL-6R levels in the presence of low IL-6 levels in serum may suggest a downregulation of sIL-6R expression of sIL-6R shedding in the presence of excessive amounts of IL-6.

Aged↗