主观睡眠质量与抑郁症患者自杀的关系

INTRODUCTIONPatientswithdepressionfrequentlyreportdisturbedsleep，includingdifficultieswithsleeponset，sleepmaintenance，andearlymorningawakening，sometimeshypersomnia．Itwassuggestedthatinsomniacouldbeanearlysymptomof，oramarkerofvulnerabilitytode－pression．Ithasbeenreportedthatdifferentkindsofdisturbedsleepmayaffectsuicidalityinbothdepressivepatientsandnormalpopu－lation犤１－２犦．Thepurposeofthisstudywastoexaminetheassociationbetweensleepqualityandsuicidalityinmajordepressivepatients…     

Alloimmunization to platelet-specific antigens on glycoproteins IIb- IIIa and Ib/IX in multiply transfused thrombocytopenic patients

The rate of alloimmunization to platelet-specific antigens associated with platelet glycoproteins (GPs) IIb-IIIa and Ib/IX was studied in 293 multiply transfused thrombocytopenic patients. Antibodies to platelet-specific antigens were measured with a solid-phase assay using platelet GP IIb-IIIa or Ib/IX as the antigenic targets. Nine patients were found to have antibodies to platelet GP IIb-IIIa, and no patients had antibodies to platelet GP Ib/IX. In six of these nine patients, the specificity of the antibody was shown by using GP IIb-IIIa from donors with different platelet-specific antigen phenotypes. In the remaining three patients with antibodies to platelet GP IIb-IIIa, no specificity could be identified. These patients had autoimmune thrombocytopenia in association with lymphoma. The alloimmunization rate to platelet-specific antigens associated with GP IIb-IIIa was 2 percent, whereas the rate of alloimmunization to HLA antigens was 23 percent. Of the patients alloimmunized to HLA antigens, 9 percent also had antibodies to platelet-specific antigens. A poor response to HLA-identical platelet transfusions was observed only in those patients with positive assays in the solid-phase test. These results suggest that the incidence of antibodies to platelet-specific antigens carried on GP IIb-IIIa is low. Platelet-specific antibodies may be found more frequently in patients alloimmunized to HLA antigens than in those not so alloimmunized.     

重组人脑利钠肽治疗心力衰竭安全性和疗效的开放性随机对照多中心临床研究

Objective To explore the safety of intravenous recombinant human brain natriuretic peptide (rhBNP) in treating acute decompensated heart failure and acute exacerbation of chronic heart failure, and to compare the differences in efficacy with different dosage and administration time. Methods A total of 2160 patients characterized of acute decompensated heart failure and acute exacerbation of chronic heart failure were enrolled in this multicenter, randomized, open, dose-control study. The patients were randomly allocated to four groups with different doses and administration time on top of standard therapy. Results In the safety respect, the rate of hypotension is 1.44% at 5 -7 days after treatment, the serum creatinine level was reduced compared to baseline( P values were 0. 0437, 0. 0087 and 0. 0116)except in the group of 0. 015 μg at 24 h (P =0. 7054). The rate of 30-day readmission is 5.65%, mortality rate is 9. 44%. In terms of efficacy, dyspnea was significantly improved at 30 min after administration, and at 24 h after administration ( all P ＜ 0. 01 ). Urine output and LEVF were also significantly increased by 76. 59% (P ＜0. 01 ) and 12. 08% respectively ( all P ＜ 0. 01 ) compared to baseline. Plasma NT-proBNP decreased by 40. 29% at 5 - 7 days after administration ( P ＜ 0. 01 ). Conclusion The clinical application of intravenous rhBNP is safe and effective for treatment of acute decompensated heart failure and acute exacerbation of chronic heart failure in this large patient cohort.     

Antihypertensive efficacy of metoprolol XL/Low dose chlorthalidone (6.25 mg) combination: a randomized,comparative study in Indian patients with mild-to-moderate essential hypertension

Objective

High blood pressure is one of the most important risk factors, directly responsible for increasing the cardiovascular morbidity and mortality. The primary objective was to evaluate the efficacy of metoprolol XL/chlorthalidone against metoprolol XL/hydrochlorothiazide with respect to mean fall in systolic and diastolic blood pressure. The secondary objective was to compare the response rates and to evaluate the tolerability of study medications in patients with mild-tomoderate essential hypertension.

Methods

Total 130 eligible patients (65: metoprolol XL 25 mg/chlorthalidone 6.25 mg; 65: metoprolol XL 25 mg/HCTZ 12.5 mg) were enrolled in this randomized, comparative, multicentric, 12-weeks study. Sixty-two patients from each group completed the study. After 4-weeks of treatment, non-responders from chlorthalidone 6.25 mg combination group were shifted to metoprolol XL 50 mg/chlorthalidone 12.5 mg and non-responders from HCTZ 12.5 mg combination group were escalated to metoprolol XL 50 mg/HCTZ 12.5 mg.

Results

The study treatment groups were comparable with respect to demography and baseline disease characteristics. Both the starting therapies were comparable with respect to mean fall in SBP (p = 0.788) and DBP (p = 0.939), and response rates (p = 1.0) after 4-weeks of therapy. Also both the step-up therapies showed similar mean fall in SBP (p = 0.277) and DBP (p = 0.507) at the end of 12-weeks. However, significantly more number of patients from chlorthalidone 12.5 mg/metoprolol XL 50 mg group responded to therapy as compared to that from HCTZ 12.5 mg/metoprolol XL 50 mg group (p = 0.045). All the reported adverse events were of mild-to-moderate intensity. There were no clinically significant trends in electrolytes (Na⁺, K⁺, Cl^-)and fasting blood sugar, evident across the treatment groups.

Conclusion

Chlorthalidone in combination with metoprolol XL is as effective and well tolerated as widely used combination of metoprolol XL/HCTZ, thus providing an alternative therapeutic option.     

Does dispositional optimism predict psychological responses to counseling for familial breast cancer?

OBJECTIVE: The present study sought to assess the ability of dispositional optimism to predict the psychological responses of women with a family history of breast cancer who had been referred to counseling for familial breast cancer. METHODS: Women completed questionnaires prior to (n=735), immediately after (n=655), and 9 months after (n=545) attending counseling. Breast cancer risk status was assessed and communicated to the women in the clinics. RESULTS: Dispositional optimism was found to predict lower levels of anxiety and breast cancer worries immediately following counseling as well as lower levels of anxiety and perceived risk at 9-month follow-up, controlling for corresponding baseline scores. In addition, risk status moderated the optimism-perceived risk relationship, such that optimism was only predictive of lower risk perceptions among women at high risk. CONCLUSIONS: Low levels of dispositional optimism may be considered to be a risk factor for adverse reactions to high breast cancer risk information. The implications of the findings for the clinical management of such reactions are discussed.     

Prediction of the effect of erythromycin, diltiazem, and their metabolites, alone and in combination, on CYP3A4 inhibition

Predictive models of complex drug-drug interactions between multiple inhibitors and their metabolites have not been evaluated. The purpose of this study was to evaluate an interaction model for cytochrome P450 3A4 (CYP3A4) that incorporated the simultaneous reversible and irreversible inhibition by multiple inhibitors. Erythromycin (ERY) and diltiazem (DTZ), and their major metabolites, N-desmethylerythromycin (nd-ERY) and N-desmethyldiltiazem (nd-DTZ), were chosen to evaluate the model. k(inact) (rate constant for maximal inactivation), K(I) (inhibitor concentration at 50% maximal inactivation), and K(i) (reversible inhibition constant) were estimated for ERY, DTZ, nd-ERY, and nd-DTZ, respectively, using cDNA-expressed CYP3A4 and human liver microsomes under optimal experimental conditions. To evaluate the interaction model, combinations of inhibitors and metabolites were incubated at concentrations equal to K(I), (1/2)K(I), and 2K(I) of each inhibitor for specified durations in both enzyme systems. The models were further evaluated by the incubation of combinations of inhibitors with the substrate testosterone for 10 min. CYP3A4 inhibition in the presence of drug mixtures was predicted from the inhibition parameters determined for each drug or metabolite alone. The CYP3A4 activity in the presence of multiple inhibitors was well predicted by the model incorporating additive irreversible inhibition as modified by mutual competitive inhibition (percent mean error and percent mean absolute error ranged from -0.06 to 0.04 and from 0.03 to 0.09, respectively). In conclusion, the additive model predicted the combined effect of multiple inhibitors on CYP3A inhibition in vitro. However, simultaneous reversible and irreversible inhibition effects should be taken into account in a reaction mixture of substrate and multiple inhibitors of CYP3A4.     

Alarin is a vasoactive peptide

Galanin-like peptide (GALP) is a hypothalamic neuropeptide belonging to the galanin family of peptides. The GALP gene is characterized by extensive differential splicing in a variety of murine tissues. One splice variant excludes exon 3 and results in a frame shift leading to a novel peptide sequence and a stop codon after 49 aa. In this peptide, which we termed alarin, the signal sequence of the GALP precursor peptide and the first 5 aa of the mature GALP are followed by 20 aa without homology to any other murine protein. Alarin mRNA was detected in murine brain, thymus, and skin. In accordance with its vascular localization, the peptide exhibited potent and dose-dependent vasoconstrictor and anti-edema activity in the cutaneous microvasculature, as was also observed with other members of the galanin peptide family. However, in contrast to galanin peptides in general, the physiological effects of alarin do not appear to be mediated via the known galanin receptors. Alarin adds another facet to the surprisingly high-functional redundancy of the galanin family of peptides.