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Background: Mild cognitive impairment (MCI) is a condition commonly associated with dementia. Therefore, early prediction of progression from MCI to dementia is essential for preventing or alleviating cognitive decline. Given that dementia affects cognitive functions like language and speech, detecting disease progression through speech analysis can provide a cost-effective solution for patients and caregivers. Design-Participants: In our study, we examined spontaneous speech (SS) and written Mini Mental Status Examination (MMSE) scores from a 60-patient dataset obtained from the Mugla University Dementia Outpatient Clinic (MUDC) and a 153-patient dataset from the Alzheimer's Dementia Recognition through Spontaneous Speech (ADRess) challenge. Our study, for the first time, analyzed the impact of audio features extracted from SS in distinguishing between different degrees of cognitive impairment using both an Indo-European language and a Turkic language, which exhibit distinct word order, agglutination, noun cases, and grammatical markers. Results: When each machine learning model was tested on its respective trained language, we attained a 95% accuracy using the random forest classifier on the ADRess dataset and a 94% accuracy on the MUDC dataset employing the multilayer perceptron (MLP) neural network algorithm. In our second experiment, we evaluated the effectiveness of each language-specific machine learning model on the dataset of the other language. We achieved accuracies of 72% for English and 76% for Turkish, respectively. Conclusion: These findings underscore the cross-language potential of audio features for automated tracking of cognitive impairment progression in MCI patients, offering a convenient and cost-effective option for clinicians or patients.

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OBJECTIVE: The female population with gestational diabetes mellitus (GDM) has a postpartum profile with increased cardiovascular (CV) risk factors and heightened prospective CV risk. Epicardial fat tissue was reported to be related to cardiometabolic diseases as metabolically active adipose tissue and natriuretic peptides (NPs) have been shown to have metabolic effects. This study's aim was to determine the relationship between epicardial fat thickness (EFT) and NPs in the female population diagnosed with GDM. PATIENTS AND METHODS: The study involved 161 pregnant women: 96 with GDM, and 65 healthy controls. GDM was diagnosed following the American Diabetes Association (2013) norms for diagnosing diabetes. All patients underwent echocardiography to measure EFT. N-terminal pro-brain natriuretic peptide (NT-proBNP) and other parameters were quantified in blood samples. The Independent Samples t-test, Pearson's correlation test, and a multivariable logistic regression analysis (LRA) were performed for statistical evaluation. A p-value <0.05 was considered statistically significant. RESULTS: Fasting (91.46±14.29 mg/dl vs. 82.18±8.21 mg/dl) (p<0.001), first-hour (202.30± 21.60 mg/dl vs. 161.57±16.21 mg/dl) (p<0.001), and second-hour (176.95±20.43 mg/dl vs. 130.93±16.95 mg/dl) glucose levels (p<0.001), fasting insulin level (14.54±3.50 mUL/mL vs. 11.51±2.04 mUL/mL; p<0.001), and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) value (3.28±0.99 vs. 2.31±0.45; p<0.0001) in GDM Group were significantly higher than Control Group. The GDM Group also had significantly increased EFT values compared to the Control Group (4.74±0.65 mm vs. 3.77±0.66 mm; p<0.0001), whereas NT-proBNP levels of diabetic women were considerably lower compared to controls (21.59±19.86 pg/ml vs. 39.74±33.96 pg/ml; p<0.0001). In addition, EFT thickness and the NT-proBNP level were determined to be significantly negatively correlated (r=-32, p<0.0001). CONCLUSIONS: EFT evaluation might play a prognostic role in detecting cardiometabolic risk associated with potential disorders such as GDM. This study showed a potential interplay between epicardial adipose tissue and NPs secreted by cardiomyocytes and practical effects on fat metabolism in GDM subjects.

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OBJECTIVE: To evaluate the effect of multiple daily injection (MDI) treatment replaced by Exenatide BID as compared with continuation of MDI. PATIENTS AND METHODS: A total of 140 patients with type 2 diabetes, taking metformin and multiple daily insulin injections, were randomized to exenatide or insulin group that continued their insulin treatment. Patients were followed-up for 16 weeks. Blood glucose profiles, BMI, waist circumference, HbA1C, serum lipids and side effects were assesssed at weeks 0,12 and 16. RESULTS: There were no significant differences between the two groups with respect to baseline parameters. Glycemic control was similar between the two groups. The mean changes in HbA1C in exenatide group were -0.66±0.63% and in insulin group -0.74±0.92 % (p=0.594). In exenatide group, 59.6 % of patients and in insulin group 85.71 % of patients had maintained or improved glycemic control at the end of the study. In insulin group, insulin requirement increased 5.86 ± 4.46 units/day. Body weight and waist circumference decreased significantly in exenatide treatment group with respect to insulin group (p<0.001). CONCLUSIONS: Substituting exenatide for insulin might be an option in insulin-treated, type 2 diabetic patients having obesity, and poor glycemic control. However, patients with longer duration of diabetes and insulin treatment and with lower C-peptide levels might not benefit from exenatide therapy.

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OBJECTIVE: To investigate the impact of body weight on the subclinical hypothyroidism observed in patients with PCOS. METHODS: The study included 95 normal weight (Group-1) and 122 overweight or obese women (Group-2) with PCOS. The control group consisted of age and BMI matched healthy individuals and grouped as normal weight (n: 66, Group-3) and overweight or obese (n: 65, Group-4. Women with chronic disease such as overt thyroid dysfunction, late-onset adrenal hyperplasia, and diabetes were excluded from the study. Plasma glucose and lipid profile, thyroid hormones, insulin, FSH, LH, total testosterone, estradiol, progesterone and DHEA-S were measured. RESULTS: While fasting glucose was similar, insulin and HOMA-IR were higher in Group-2 and Group-4 (p: 0.001). The groups were similar with respect to FSH, Estradiol, prolactine, DHEAS. While total testosterone and LH levels were higher (ptestosterone: 0,009), progesterone was lower in both PCOS groups (pprogesterone: 0.041). Free T3, free T4, thyroid antibodies were similar between the groups, but the prevalence of subclinical hypothyroidism was greater in Group-2 and -4 than in Group-1 and -3 (p: 0.044). TSH was only correlated with BMI (r: 0.122, p: 0.02). CONCLUSION: The increased prevalence of subclinical hypothyroidism in women with PCOS might be the result of increased BMI.

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OBJECTIVES: The objective of this paper is to describe some of the major healthcare information technology (IT) infrastructures in Turkey, namely, Saglik-Net (Turkish for "Health-Net"), the Centralized Hospital Appointment System, the Basic Health Statistics Module, the Core Resources Management System, and the e-prescription system of the Social Security Institution. International collaboration projects that are integrated with Saglik-Net are also briefly summarized. METHODS: The authors provide a survey of the some of the major healthcare IT infrastructures in Turkey. RESULTS: Saglik-Net has two main components: the National Health Information System (NHIS) and the Family Medicine Information System (FMIS). The NHIS is a nation-wide infrastructure for sharing patients' Electronic Health Records (EHRs). So far, EHRs of 78.9 million people have been created in the NHIS. Similarly, family medicine is operational in the whole country via FMIS. Centralized Hospital Appointment System enables the citizens to easily make appointments in healthcare providers. Basic Health Statistics Module is used for collecting information about the health status, risks and indicators across the country. Core Resources Management System speeds up the flow of information between the headquarters and Provincial Health Directorates. The e-prescription system is linked with Saglik-Net and seamlessly integrated with the healthcare provider information systems. Finally, Turkey is involved in several international projects for experience sharing and disseminating national developments. CONCLUSION: With the introduction of the "Health Transformation Program" in 2003, a number of successful healthcare IT infrastructures have been developed in Turkey. Currently, work is going on to enhance and further improve their functionality.

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OBJECTIVE: To investigate the relationship between development of laryngeal cancer and the presence of polymorphisms of the MnSOD Val16Ala, CAT-262 C < T and GPx1 Pro198Leu genes in a smoking population. PATIENTS AND METHODS: Single nucleotide polymorphisms were determined in DNA from the peripheral blood erythrocytes of 48 heavy smokers (25 patients with laryngeal cancer and 23 cancer-free controls), using polymerase chain reaction. RESULTS: There were no significant differences in age, smoking duration or smoking intensity, comparing the two groups. The homozygous AA genotype of MnSOD Val16Ala was significantly more prevalent in the cancer group than the control group (92 vs 13 per cent, respectively), while the heterozygous AV genotype of MnSOD Val16Ala was more prevalent in the control group than the cancer group (87 vs 8 per cent, respectively) (p < 0.001). There were no significant differences between the cancer and control groups regarding GPx1 Pro198Leu or CAT-262 C < T polymorphisms. CONCLUSION: Polymorphism of the MnSOD Val16Ala gene may contribute to susceptibility to laryngeal cancer among smokers.

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OBJECTIVES: The objective of this paper is to describe the techniques used in developing the National Health Information System of Turkey (NHIS-T), a nation-wide infrastructure for sharing electronic health records (EHRs). METHODS: The UN/CEFACT Core Components Technical Specification (CCTS) methodology was applied to design the logical EHR structure and to increase the reuse of common information blocks in EHRs. RESULTS: The NHIS-T became operational on January 15, 2009. By June 2010, 99% of the public hospitals and 71% of the private and university hospitals were connected to NHIS-T with daily feeds of their patients' EHRs. Out of the 72 million citizens of Turkey, electronic healthcare records of 43 million citizens have already been created in NHIS-T. Currently, only the general practitioners can access the EHRs of their patients. In the second phase of the implementation and once the legal framework is completed, the proper patient consent mechanisms will be available through the personal health record system that is under development. At this time authorized healthcare professionals in secondary and tertiary healthcare systems can access the patients' EHRs. CONCLUSIONS: A number of factors affected the successful implementation of NHIS-T. First, all stakeholders have to adopt the specified standards. Second, the UN/CEFACT CCTS approach was applied which facilitated the development and understanding of rather complex EHR schemas. Finally, the comprehensive testing of vendor-based hospital information systems for their conformance to and interoperability with NHIS-T through an automated testing platform enhanced substantially the fast integration of vendor-based solutions with the NHIS-T.

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Tuberculosis is seen with an increased frequency in cancer patients. Possible reasons of reactivation are thought to be related to chemotherapy and insufficient nutrition together with compromised immune system. The diagnosis of tuberculosis may be missed in cancer patients and may be diagnosed with newly developed radiological and clinical findings during treatment. In this case, tuberculosis should be considered and related diagnostic work up should be completed. Also, PPD test should be applied to cancer patients and if needed isoniazid prophylaxis should be initiated. We present herein 4 cancer patients diagnosed with pulmonary tuberculosis. Two patients suffered from solid malignancies (lung cancer) and 2 from non-solid malignancies (acute myeloid leukemia).

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BACKGROUND: There is consisting evidence that asthma is associated with airway inflammation. Originally IL-10 and IL-2 were described as lymphokines produced by T cells in mediating cellular infiltration into the airways and continue to be of interest in evaluating asthma pathogenesis. The aim of this study was to evaluate the serum and sputum levels of IL-2 and IL-10 in asthmatic subjects and healthy controls and to correlate disease activity and other clinical indices with concentrations of IL-2 and IL-10 in serum and sputum samples. METHODS: We evaluated cell profiles and IL-2 and IL-10 levels in induced sputum samples and in serum samples of 6 mild, 5 moderate, 7 severe asthmatic patients and 5 healthy controls by using ELISA. RESULTS: The mean IL-2 in sputum samples of asthmatics and controls were 35.3 +/- 13.2 pg/ml and 35.3 +/- 8.4 pg/ml, respectively. The mean IL-2 in serum samples of asthmatics and controls were 42.7 +/- 21.1 pg/ml and 30.3 +/- 2.4 pg/ml, respectively. Both levels did not result in any statistically significant difference between asthmatics and controls. There was no correlation between serum and sputum IL-2 levels, however sputum IL-2 levels correlated with percentage of sputum lymphocytes (p < 0.03, r = 0.51). The mean IL-10 levels in sputum samples of asthmatics and controls were 4.4 +/- 3.3 pg/ml and 3.9 +/- 5.9 pg/ml, respectively, the mean IL-10 level in serum of asthmatics and controls were 4.1 +/- 3.8 pg/ml and 2.3 +/- 2.5 pg/ml, respectively. We could not find statistically significant difference of serum or sputum IL-10 levels between asthmatics and controls. There was only correlation between serum and sputum IL-10 levels in asthmatics (p < 0.0008, r = 0.73). There was no difference between asthmatic subgroups regarding sputum and serum levels of IL-2 and IL-10. No correlation could be demonstrated between sputum or serum IL-2 and IL-10 levels and clinical severity. CONCLUSIONS: We have demonstrated the presence of detectable concentrations of the IL-2 and IL-10 in serums and induced sputum samples of asthmatics, however, they have no predictive value for asthma since their levels are not increased in asthmatic patients over controls. Moreover, IL-2 level positively correlated with lymphocyte percentage in induced sputum. The results suggest that measurement of IL-2 and IL-10 concentrations in serum and sputum will not be of diagnostic use in asthma and a reflection of the severity of asthmatic airway inflammation.

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Adrenomedullin (ADM) is a newly discovered endogenous vasorelaxing peptide isolated from pheochromocytoma. Some experimental studies suggest that ADM plays a role in asthma. The purposes of the present study were to assess the plasma ADM levels in adults with mild to severe asthma and controls and to correlate those with the findings on lung function test results and other clinical indices. We recruited 16 mild, 10 moderate, and 11 severely asthmatic patients and 12 healthy controls. We measured the plasma concentrations of ADM in patients with asthma and in healthy subjects using RIA. We assessed FEV1, FEV1 predicted %, FEV1/FVC, symptom score, IgE, ECP, and morning and evening peak expiratory flow measurements. There was no significant difference between the asthmatic and the control group ADM levels, which were 26.3 +/- 24.2 pg/mL and 22.9 +/- 17.6 pg/mL, respectively. Furthermore, plasma ADM levels increased as the severity of the disease increased in asthmatic patients (20.7 +/- 14.4 pg/mL in mild, 25.2 +/- 24.3 pg/mL in moderate, and 35.5 +/- 33.6 pg/mL in severe asthmatics), although they did not result in any statistical significance. However, the plasma ADM levels correlated negatively with the FEV1 levels in the asthmatic group (p < 0.02, r = -0.37). Peripheral blood eosinophilia, IgE, and ECP levels did not correlate with plasma ADM levels. These results suggest that the measurement of ADM concentration in plasma will not be of diagnostic use in asthma, but may be a reflection of the severity of asthma.

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OBJECTIVES: Recent studies have shown that inhaled standard heparin exhibits protection towards various bronchoconstrictor stimuli in asthma including methacholine. Low molecular weight heparins (LMWH) (4000-5000 daltons) have higher bioavailability than standard heparins (12,000-16,000 daltons). It is possible that the anti-asthmatic activity of heparin may be molecular weight-dependent. The purpose of the present investigation was to study the effect of LMWH on methacholine-induced bronchoconstriction and to compare the effect of LMWH with that of standard heparin. SUBJECTS: Fifteen subjects (7 male, 8 female, mean age: 33 +/- 13 years, range: 20-65) with mild asthma were studied. METHOD: Methacholine bronchial provocation tests were performed in a single-blind, crossover, randomized order and repeated 45 minutes after placebo or aerosolized standard heparin (1.000 U/kg) or aerosolized LMWH (Enoksaparin, Clexane, 0.8 mg/kg). RESULTS: There was no significant difference in baseline FEV1 values between study days. The standard heparin and enoksaparin inhibited bronchoconstriction induced by methacholine. The geometric mean log PD20 values after placebo, standard heparin, and enoksaparin were 0.24 +/- 0.57 (1.74) mg/ml, 0.79 +/- 0.59 (6.17 mg/ml), 0.76 +/- 0.57 (5.75 mg/ml), respectively (p < 0.0009). Three subjects in standard heparin group and two subjects in enoksaparin group showed increased hyperreactivity, the others showed decreased bronchial hyperreactivity. The degree of protection offered by standard heparin and enoksaparin did not show any statistical difference. CONCLUSIONS: These data suggest that both inhaled LMWH and inhaled standard heparin play inhibitory roles in methacholine-induced bronchoconstriction.

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Covalent DNA-streptavidin conjugates are versatile biomolecular coupling reagents, since they have binding capacity for both a complementary nucleic acid and four molecules of biotin. The DNA-streptavidin hybrid molecules have been investigated for their capabilities to bind two different types of biotinylated components. Thus, (i) a functional biomolecule, e.g., a single-stranded DNA fragment or an enzyme and (ii) low-molecular weight biotin derivatives ("modulators") were coupled stepwise with the hybrid molecules. Modulators were D-biotin, aminobiotin, and biotin-fluorescein conjugate as well as a lysine-rich 10mer peptide, containing a biotin and a fluorescein substituent. These modulators were chosen to affected the hybridization properties of the DNA-streptavidin conjugates. As investigated by surface-plasmon resonance and microplate solid-phase hybridization measurements, D-biotin, biotin-fluorescein, and aminobiotin decreased the efficiency of hybridization with complementary, surface-bound oligonucleotides to a varying extent. The basic peptide increased the conjugate's hybridization efficiency. Moreover, it was demonstrated in two examples how modulators can be utilized as additional functional domains of streptavidin-based conjugates. First, fluorescein-containing modulators were used as hapten groups, allowing a sensitive detection by means of specific antibodies directed against the modulator. Second, the biotinylated peptide was used as a carrier molecule to attach multiple fluorogenic lanthanide-chelate groups to the streptavidin conjugate, enabling its sensitive detection by time-resolved fluorometry. The applicability of this kind of bioconjugation strategy to generate sensor-probes for gene detection assays was demonstrated.

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Covalent DNA-streptavidin conjugates have been utilized for the reversible and site-selective immobilization of various biotinylated enzymes and antibodies by DNA-directed immobilization (DDI). Biotinylated alkaline phosphatase, beta-galactosidase, and horseradish peroxidase as well as biotinylated anti-mouse and anti-rabbit immunoglobulins have been coupled to the DNA-streptavidin adapters by simple, two-component incubation and the resulting preconjugates were allowed to hybridize to complementary, surface-bound capture oligonucleotides. Quantitative measurements on microplates indicate that DDI proceeds with a higher immobilization efficiency than conventional immobilization techniques, such as the binding of the biotinylated proteins to streptavidin-coated surfaces or direct physisorption. These findings can be attributed to the reversible formation of the rigid, double-stranded DNA spacer between the surface and the proteins. Moreover, BIAcore measurements demonstrate that DDI allows a reversible functionalization of sensor surfaces with reproducible amounts of proteins. Ultimately, the simultaneous immobilization of different compounds using microstructured oligonucleotide arrays as immobilization matrices demonstrate that DDI proceeds with site selectivity due to the unique specificity of Watson-Crick base pairing.

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Current developments in nanosciences indicate that the self-assembly of macromolecules, such as proteins or metallic nanoclusters, can be conveniently achieved by means of nucleic acid hybridization. Within this context, we here report on the evaluation of single-stranded nucleic acids to be utilized as carrier backbones in DNA-directed self-assembly. A microplate solid-phase hybridization assay is described which allows rapid experimental determination of the hybridization efficiencies of various sequence stretches within a given nucleic acid carrier strand. As demonstrated for two DNA fragments of different sequence, the binding efficiencies of several oligonucleotides depend on the formation of specific secondary structure elements within the carrier molecule. A correlation of sequence-specific hybridization capability with modeled secondary structure is also obvious from experiments using the fluorescence gel-shift analysis. Electrophoretic studies on the employment of helper oligonucleotides in the formation of supramolecular conjugates of several oligonucleotide-tagged proteins indicate, that structural constraints can be minimized by disruption of intramolecular secondary structures of the carrier molecule. To estimate the influences of the chemical nature of the carrier, gel-shift experiments are carried out to compare a 170mer RNA molecule with its DNA analogue. Ternary aggregates, containing two protein components bound to the carrier, are formed with a greater efficiency on the DNA instead of the RNA carrier backbone.

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Airway inflammation plays a pivotal role in asthma. Over the last 10 years, evidence has accumulated for the potential role of lymphocytes in airway inflammation. Since cyclosporin A (Cyc-A) can profoundly influence lymphocyte activation, it is appropriate to consider this drug as a novel antiasthmatic. The effect of inhalation of low doses of Cyc-A on airway inflammation remains unclear. The purpose of this study was to investigate the bronchoalveolar lavage (BAL), peripheral blood cell profiles, and lung biopsy specimens in Cyc-A-pretreated rats. Twenty-nine rats (8 controls, 10 ovalbumin sensitized, and 11 Cyc-A inhaling and ovalbumin sensitized) were included in the study. A commercial intravenous Cyc-A solution was given as a single dose of 20 mg/kg 1 h prior to inhalation of ovalbumin via nebulizer. The total number of BAL cells significantly increased in rats inhaling Cyc-A when compared with ovalbumin-sensitized rats (2.37 +/- 2.34 x 10(6)/ml and 1.01 +/- 0.49 x 10(6)/ml respectively, p < 0.05). There was a significant increase in the percentage of lymphocytes (14.5 +/- 8.5 versus 27.4 +/- 7.4%, p < 0.03), a nonsignificant increase in the percentage of eosinophils (0.8 +/- 1.0 versus 3.0 +/- 4.6%), and a significant decrease in the percentage of polymorphonuclear leukocytes (9.4 +/- 6.9 versus 3.4 +/- 3.8%, p < 0.01) and macrophages (75.4 +/- 5.1 versus 50.2 +/- 11.8%, p < 0.02) in BAL in the ovalbumin-sensitized group as compared with controls. Differential cell counts revealed a higher percentage of neutrophils and macrophages in the BAL of Cyc-A-pretreated rats than in that of the ovalbumin-sensitized group (26.3 +/- 26.8 versus 3.4 +/- 3.8%, p < 0.01 and 66.1 +/- 7.7 versus 50.2 +/- 11.8%, p < 0.02). There was a nonsignificant decrease of lymphocytes and eosinophils in the Cyc-A-pretreated group when compared with the ovalbumin-sensitized group (27.4 +/- 7.4 versus 21.1 +/- 12.4 and 3.0 +/- 4.6% versus 2.4 +/- 2.6%). The peripheral blood total white blood cell count decreased in the ovalbumin-sensitized and Cyc-A-pretreated groups as compared with the control group (2,520 +/- 1,098/mm3, 3,591 +/- 2,251/mm3, and 5,975 +/- 2,787/mm3, respectively, p < 0.01). In addition, peripheral eosinophilia was detected in the Cyc-A-pretreated group when compared with controls and the ovalbumin-sensitized group (6.9 +/- 4.7, 2.4 +/- 1.1, and 2.6 +/- 2.4%, respectively, p < 0.01). Light-microscopic examination of the airways revealed prominent eosinophilia in tracheal, bronchial, and bronchiolar sections in the ovalbumin-sensitized group: counts were 1.8 +/- 2.3/HPF, 10.3 +/- 11.4/HPF, 63.3 +/- 45.0/HPF, respectively. Cyc-A resulted in a decrease of the eosinophil counts/HPF to 0/HPF in trachea (p < 0.05), to 4.3 +/- 9.4/HPF in bronchi (p < 0.02), to 19.4 +/- 38.4 in bronchioles (p < 0.004). In conclusion, the present study supports the theory that locally administered inhaled low-dose Cyc-A is effective on inflammatory cells of sensitized airways and peripheral cells. It may therefore be useful in elucidating the inflammatory mechanisms involved in asthma.

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STUDY OBJECTIVE: To compare the efficacy of standard medical therapy (ST) and noninvasive mechanical ventilation additional to standard medical therapy in hypercapnic acute respiratory failure (HARF). DESIGN: Single center, prospective, randomized, controlled study. SETTING: Pulmonary medicine directed critical care unit in a university hospital. PATIENTS: Between March 1993 and November 1996, 30 HARF patients were randomized to receive ST or noninvasive positive pressure ventilation (NPPV) in addition to ST. INTERVENTIONS: NPPV was given with an air-cushioned face via a mechanical ventilator (Puritan Bennett 7200) with initial setting of 5 cm H2O continuous positive airway pressure and 15 cm H2O pressure support. RESULTS: At the time of randomization, patients in the ST group had (mean+/-SD) PaO2 of 54+/-13 mm Hg, PaCO2 of 67+/-11 mm Hg, pH of 7.28+/-0.02, and respiratory rate of 35.0+/-5.8 breaths/min. Patients in the NPPV group had PaO2 of 55+/-14, PaCO2 of 69+/-15, pH of 7.27+/-0.07, and respiratory rate of 34.0+/-8.1 breaths/min. With ST, there was significant improvement of only respiratory rate (p < 0.05). However, with NPPV, PaO2 (p < 0.001), PaCO2 (p < 0.001), pH (p < 0.001), and respiratory rate (p < 0.001) improved significantly compared with baseline. Six hours after randomization, pH (p < 0.01) and respiratory rate (p < 0.01) in NPPV patients were significantly better than with ST. Hospital stay for NPPV vs ST patients was, respectively, 11.7+/-3.5 and 14.6+/-4.7 days (p < 0.05). One patient in the NPPV group required invasive mechanical ventilation. The conditions of six patients in the ST group deteriorated and they were switched to NPPV; this was successful in four patients, two failures were invasively ventilated. CONCLUSION: This study suggests that early application of NPPV in HARF patients facilitates improvement, decreases need for invasive mechanical ventilation, and decreases the duration of hospitalization.

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Glycosaminoglycan heparin possesses multiple noncoagulant properties including antiinflammatory actions. We have previously shown that heparin attenuates the methacholine-induced bronchoconstriction in humans. In contrast to methacholine, a stimulus that induces airway constriction mainly by "direct" stimulation of airway smooth muscle cells, adenosine airway responsiveness reflects "indirectly" induced airway narrowing via inflammatory mediators or neural reflex mechanisms. Whether heparin modulates bronchial hyperreactivity induced by adenosine, is not well known. We investigated the effect of inhaled heparin on adenosine-induced bronchoconstriction and compared the inhibitory role of heparin on the adenosine challenge test with that on the methacholine challenge test. Fifteen subjects (7 males, 8 females) with mild asthma were included in the study. Bronchial provocation tests were performed in a single-blind, crossover, randomized order, and repeated 45 minutes after placebo or aerosolized heparin inhalation (1,000 U/kg). The heparin increased the geometric mean log methacholine PD20 value from 0.47 +/- 0.16 (2.95 mg/ml) to 0.96 +/- 0.10 (8.91 mg/ml), (P < 0.0009) in 15 patients and the geometric mean log adenosine PD20 values from 1.59 +/- 0.23 (38.9 mg/ml) to 1.98 +/- 0.14 (97.7 mg/ml) (NS) in 7 patients whose baseline adenosine PD20 levels were less than 200 mg/ml. The degree of protection by heparin against adenosine-induced bronchoconstriction was not correlated with that against methacholine-induced bronchoconstriction (r = 0.60, NS). The data suggest that inhaled heparin may have an inhibitory effect on the methacholine bronchial challenge, and thus, most likely directs its effect against smooth muscle. Heparin caused less attenuation of a challenge with adenosine and probably does not affect mast cell degranulation.

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BACKGROUND: There is some evidence that the perception of bronchoconstriction may very according to the nature of the provoking stimulus. The aims of this study were, firstly, to develop a method for measuring dyspnoea during induced bronchoconstriction in patients with asthma and, secondly, to apply this method to testing differences between directly and indirectly acting bronchoconstricting stimuli. METHODS: Descriptive terms suitable for quantifying respiratory discomfort due to bronchoconstriction in patients with asthma were identified in a preliminary investigation. The relation between reduction in forced expiratory volume in one second (FEV1) and respiratory discomfort, measured using a visual analogue scale (VAS), was then studied during challenges with three different inhaled stimuli: methacholine (MCH), sodium metabisulphite (MBS), and adenosine monophosphate (AMP). Three indices were calculated to describe the relation: the VAS value associated with a 20% fall in FEV1 (FEV20 VAS); the ratio of the final VAS value to the final percentage fall in FEV1 (VAS-FEV1 ratio); and the regression coefficient for predicting VAS from the percentage fall in FEV1 within each challenge (beta VAS FEV1). RESULTS: "Difficulty in breathing" and "chest tightness" were selected as suitable terms for quantifying respiratory discomfort. There were no differences between the three agonists in the qualitative aspects of the respiratory sensation. In paired challenges with the same agonist the three indices were all found to be reproducible for both sensations measured. MCH induced less intense difficulty in breathing and chest tightness for a given fall in FEV1 than did AMP. There was a trend in the same direction for the comparison between MCH and MBS. There were no differences between AMP and MBS. FEV20 VAS was less powerful in discriminating between agonists than the two slope indices. CONCLUSIONS: The relation between induced reduction in FEV1 and the intensity of respiratory discomfort can be measured reliably. The indirectly acting bronchoconstricting agonists AMP and MBS induced more intense respiratory discomfort for a given fall in FEV1 than the direct agonist MCH. This may be due to differences in unmeasured mechanical changes in the lungs or to an additional action on airway sensory nerves.

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