Optimal cut-off value of serum procalcitonin in predicting bacterial infection induced acute exacerbation in chronic obstructive pulmonary disease: A prospective observational study.

OBJECTIVE: To explore the optimal cut-off value of serum procalcitonin (PCT) level in predicting bacterial infection in hospitalized patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). METHODS: 204 hospitalized patients with AECOPD were enrolled in this study. Their diagnoses and treatments followed routine protocols in Fu-Xing Hospital affiliated to Capital Medical University, Beijing, China. Extra blood samples were taken for serum PCT level testing and the results were blinded to the treating physicians. On discharge, clinical data were collected and the treating physicians made comprehensive analyses to determine whether the AECOPD were triggered by respiratory tract bacterial infection or non-bacterial causes according to the "new diagnostic criteria" defined in this study. In the AECOPD patients with bacterial infection, treating physicians decided whether they had bacterial pneumonia based on imaging studies. Receiver operating characteristic curve (ROC) was used to analyze the accuracy of serum PCT level in predicting bacterial infection. RESULTS: In the 173 AECOPD patients who did not have pneumonia, 115 had evidences of bacterial infection while 58 did not. The median PCT levels were 0.1(0.08, 0.18) ng/ml and 0.07 (0.05, 0.08) ng/ml for each group, which were statistically different. The proposed optimal cut-off value of serum PCT level in predicting bacterial infection was 0.08 ng/mL according to this study, with a sensitivity of 81%, specificity of 67% and area under the ROC curve (AUC) of 0.794. There were 31 AECOPD patients diagnosed with pneumonia, their median PCT level was 0.23 ng/mL. CONCLUSIONS: The serum PCT levels slightly increased in the majority of hospitalized patients with AECOPD compared with reference range. When PCT level was ≥0.08 ng/mL, AECOPD was more likely to be caused by bacterial infection. A significantly elevated PCT levels may indicate combination of AECOPD and bacterial pneumonia.

[Effects of bio-organic fertilizer and fungicide application on continuous cropping obstacles of cut chrysanthemum].

Abstract: Fusarium wilt is a soil borne disease caused by plant continuous cropping in monoculture Chrysanthemum morifolium 'Youxiang' monoculture not only declines plant quality and yield but also decreases soil enzymes and soil microbial diversity over successive cultivation. In this article, the effects of fungicide (Carbendazim MBC), antifungal enhanced bio-organic fertilizer (BOF), and their combined application on the quality and soil enzymes activities of Chrysanthemum morifolium 'Youxiang' in continuous cropping systems were investigated. The results showed that both bioorganic fertilizer (BOF) and fungicide (MBC) single application could effectively prevent the occurrence of Fusarium wilt disease of cut chrysanthemum. Bio-organic fertilizer application was more effective on root activity, soil enzymes activities and quality (shoot height, stem diameter, leaf SPAD value, ray floret number, shoot fresh mass) improvement of cut chrysanthemum, while fungicide single application was responsible for soil enzymatic activities suppression to some extent. The combined application treatment (MBC+BOF) showed the best effects on quality improvement and soil enzyme activities promotion.

[The diagnostic values of Wells score and modified Geneva score for pretesting acute pulmonary embolism: a prospective study].

OBJECTIVE: To assess the diagnostic predictive value of Wells score and modified Geneva score for acute pulmonary embolism by prospective case series and to explore a more suitable scoring system for Chinese population. METHODS: All the patients suspected of pulmonary embolism (PE) and received CT pulmonary angiography (CTPA) were enrolled consecutively in Fuxing Hospital, Capital Medical University, China, from June 2009 to August 2011. Before CTPA test or on condition that test results were unknown, clinical scoring was assessed prospectively by the Wells score and the modified Geneva score. The probability of PE in each patient was assessed and the patients were divided into low, moderate and high probability groups according to the clinical scores. The result of CTPA was used as the diagnostic gold standard for PE. Diagnostic accuracy in each group was analyzed. The predictive accuracy of both scores was compared by AUC(ROC) curve. RESULTS: A total of 139 patients met our enrollment criteria and 117 eligible patients entered our study at last. PE was diagnosed in 47 patients by CTPA with an overall prevalence of 40.2%.Prevalence of PE in the low, moderate and high pretest probability groups assessed by the Wells score and by the simplified modified Geneva score were 7.1% (3/42), 42.9% (21/49), 88.5% (23/26) and 10.0% (3/30), 48.1% (37/77), 7/10, respectively. AUC(ROC) curves for the Wells score and the simplified modified Geneva score were 0.872 (95%CI 0.810 - 0.933) and 0.734 (95%CI 0.643 - 0.825) respectively, with a significant difference (P = 0.005). CONCLUSION: The Wells score is more accurate for clinical predicting acute PE than the modified Geneva score.

[Changes in pulmonary function in SARS patients during the three-year convalescent period].

OBJECTIVE: To investigate the patterns of pulmonary function in severe acute respiratory syndrome (SARS) patients during three-year convalescent period, and to investigate the changes and the medium and long term effects on pulmonary function of SARS patients. METHODS: Pulmonary function tests were conducted for four times in 37 SARS patients during three-year convalescent period. They were discharged from hospital within one month, three months, one year and three years respectively. At the same time, pulmonary function of 15 healthy persons was examined as controls to be used for comparison. RESULTS: Compared with the healthy controls, there were significant decrease in forced vital capacity (FVC), vital capacity (VC), one second forced expiratory volume (FEV1), 25%-75% forced expiratory flow (25%-75%FEF) of SARS patients within three years after their discharge from hospital (all P<0.05). There were no significant differences in FEV1/FVC, total lung capacity (TLC), diffusing capacity of the lung for carbon monoxide (DLCO) between the two groups (all P>0.05). Abnormality rate of DLCO in the SARS patients within three years after discharge was significantly decreased (32.4% vs. 5.4%,P<0.05), but no significant differences in FVC, VC, 25%-75%FEF among SARS patients discharged one month and three years from the hospital (all P>0.05). Ten SARS patients showed lower FVC (mild degree in 9 cases, severe degree in 1 case) three years later, 2 patients showed mildly lowered DLCO. CONCLUSION: The lung diffusion function of the SARS patients had recovered after they were discharged from hospital within three years, but in 20%-30% patients there is still mild or moderate restrictive ventilation function abnormality and small airway function impairment. The lung functions of most patients have recovered gradually, but in a minority of patients they may be impaired.

Synthesis, molecular modeling, and biological studies of novel piperidine-based analogues of cocaine: evidence of unfavorable interactions proximal to the 3alpha-position of the piperidine ring.

A qualitative model for the binding pocket proximal to the 3alpha-substituent of the piperidine-based monoamine transporter ligands was proposed and tested. Based on this model, a new series of druglike 3alpha-modified piperidine-based analogues of cocaine were designed, synthesized, and studied for their ability to inhibit reuptake of DA, 5-HT, and NE by the DA, 5-HT, and NE transporters. We found that the insertion of at least one additional methylene group between the piperidine ring and the polar group in the 3alpha-substituent dramatically improves the activity of the compounds that are generally inactive without this additional linker. Molecular modeling analysis showed that the more flexible 3alpha-substituents can avoid unfavorable interactions with the binding sites of DAT, SERT, and NET. The present results may have important implications for the elucidation of the structural differences between DA, 5-HT, and NE transporters and for the further design of new leads for development of cocaine abuse medication as well as certain neurological disorders such as ADHD and depression.

Biaryl analogues of conformationally constrained tricyclic tropanes as potent and selective norepinephrine reuptake inhibitors: synthesis and evaluation of their uptake inhibition at monoamine transporter sites.

A series of novel conformationally constrained tricyclic tropane derivatives containing a biaryl moiety, (Z)-9-(biarylylmethylene)-7-azatricyclo[4.3.1.0(3,7)]decanes, were synthesized and evaluated for their ability to inhibit reuptake of dopamine (DA), serotonin (5-HT), and norepinephrine (NE) by the DA, 5-HT, and NE transporters. Most of the compounds containing a methoxycarbonyl substituent at C-10 exhibit moderate to high inhibitory activity at the NET but lower activity at the DAT and SERT. Among these new compounds, some potent, NET-selective ligands were identified. The p-methoxy derivative 11a has a K(i) value of 39 nM for uptake inhibition at the NET and moderate to high selectivity over the SERT (100-fold) and the DAT (20-fold). Compound 11f exhibits a remarkable potency (K(i) = 9.7 nM) at the NET and a 25-fold selectivity over both the SERT and the DAT. Analogue 23 containing a thiophene ring as a bioisosteric replacement of the phenyl ring Ar(1) displays a high activity (K(i) = 10.3 nM) for the NET and similar selectivity over the SERT (50-fold) and the DAT (37-fold). The selectivity profile of biaryl analogues differs from that of the monoaryl series, as most members of that series display excellent potency at and selectivity for the SERT (J. Med. Chem. 2002, 45, 1930). This finding suggests that the different shape and size of the lipophilic recognition pocket that encompasses the aryl ring(s) of these tropanes are major determinants of a ligand's transporter activity at either the NET or the SERT. Some of the compounds in this series may also be valuable in sorting out the contribution of the individual transporters to cocaine's reinforcing properties.

SAR studies of piperidine-based analogues of cocaine. 4. Effect of N-modification and ester replacement.

A series of novel N- and 3alpha-modified piperidine-based analogues of cocaine were synthesized and tested for their ability to inhibit reuptake of DA, 5-HT, and NE by the DA, 5-HT, and NE transporters. N-Demethylation of trans-(+)-3alpha-piperidine-based ligands leads to improved activity at the SERT and NET and modest changes at the DAT. Replacement of the N-methyl group in trans-(+)-ester 1a with phenylalkyl groups leads to a modest 2.3-fold improvement in activity at the SERT (K(i) < or = 3.27 microM), insignificant changes at the NET, and a 3.5-fold loss in activity at the DAT (K(i) > or = 810 nM); however, such replacement in cis-(-)-ester 4, the more potent isomer of 1a, leads, in general, to a significant decrease in activity at all monoamine transporters (K(i) > 1 microM). Other N-modified ligands, including the ligands with polar groups incorporated in the N-alkyl substituent (3e-g) and ligands lacking the basic nitrogen (3i and 6d), show decreased activity at all monoamine transporters, though ligands 3e-g are similar in potency at the NET to 1a. N-Norester 2a, a possible metabolite of the lead compound 1a, and alcohol 1c, a compound with a 3alpha-substituent that is more stable to metabolism than 1a, were selected for further behavioral tests in animals. Alcohol 1c and ester 2a are similar in potency at the DAT to cocaine, ester 1a, and oxadiazole 1b, and both fully substitute for cocaine and have potency similar to that of cocaine in drug discrimination tests. Like cocaine, 1c increased locomotor activity (LMA) monotonically with time, whereas 2a produces biphasic effects consisting of initial locomotor depression followed by delayed locomotor stimulation. An interesting difference between cocaine, ester 1a, alcohol 1c, and N-norester 2a is that 1c and 2a are significantly longer acting in LMA tests. Although this result was anticipated for alcohol 1c, it is rather surprising for 2a which has an ester function susceptible to hydrolysis, a pathway of in vivo deactivation of cocaine and its ester analogues. The present results may have important implications for our understanding of the pharmacological mechanisms underlying the behavioral actions of cocaine and of the structural features needed for the design of the new leads in the discovery of a cocaine abuse medication.