HPLC-MAXPLOT UV检测法测定血清中丹那唑及其代谢产物

本文建立了同时测定人体血清中丹那唑(Ⅰ)及其主要代谢产物2-羟甲基妊娠素(Ⅱ)和其它代谢产物妊娠素(Ⅲ)的高效液相色谱法。方法用YWG C18柱并以甲醇—水(74:26)作为流动相,应用紫外最大吸收作图法(maxplot)检测技术,以UV 285,240nm分别测定Ⅰ,Ⅱ和Ⅲ。使原型药和代谢产物都达到较高检测灵敏度。同时对方法的专一性、准确性和精密度等方面进行了评价,并应用于临床监测。     

Effects of bromowillardiine and willardiine on non-N-methyl-D-aspartate receptors in postnatal rat hippocampal neurons.

The physiology and pharmacology of willardiine and bromowillardiine, structural analogues of quisqualate, were studied in cultured postnatal rat hippocampal neurons using whole-cell voltage-clamp techniques. These agonists appear to act at a shared non-N-methyl-D-aspartate (non-NMDA) receptor-channel complex and gate nonselective cationic currents. Willardiine currents desensitize rapidly and to a much greater degree than bromowillardiine currents. In addition, the brominated compound produces steady state currents that are 5 times larger than those produced by willardiine at saturation. Bromowillardiine is also a more efficacious excitotoxin, producing about 3-fold greater acute neuronal damage than willardiine at saturating concentrations. These results suggest that agonist structure affects the ability of non-NMDA agonists to induce desensitization and add support to the hypothesis that receptor desensitization serves to limit acute excitotoxicity in cultured neurons.     

Serum alkaline phosphatase and 30-day mortality after surgery for spinal metastatic disease

Background

Elevated serum alkaline phosphatase has been previously studied as a biomarker for progression of metastatic disease and implicated in adverse skeletal events and worsened survival. The purpose of this study was to determine if serum alkaline phosphatase was a predictor of short-term mortality of patients undergoing surgery for spinal metastatic disease.

Methods

The American College of Surgeons National Surgical Quality Improvement Program was queried for patients undergoing spinal surgery for metastatic disease. Bivariate and multivariable analyses was undertaken to determine the relationship between serum alkaline phosphatase and 30-day mortality.

Results

For the 1788 patients undergoing operative intervention for spinal metastatic disease between 2009 and 2016 the 30-day mortality was 8.49% (n?=?151). In patients who survived beyond 30-days after surgery, n?=?1627 (91.5%) the median [interquartile range] serum alkaline phosphatase levels were 126.4 [75–138], whereas in patients who had 30-day mortality, the serum alkaline phosphatase levels were 179.8 [114–187]. The optimal cut-off for alkaline phosphatase was determined to be 113 IU/L. On multivariable analysis, elevated serum alkaline phosphatase levels were associated with 30-day mortality (OR?1.61, 95% CI?1.12–2.32, p?=?0.011).

Conclusion

Elevated preoperative serum alkaline phosphatase is a marker for 30-day mortality in patients undergoing surgery for spinal metastatic disease. Future retrospective and prospective study designs should incorporate assessment of this serum biomarker to better understand the role for serum alkaline phosphatase in improving prognostication in spinal metastatic disease.

     

Physician support for diabetes patients and clinical outcomes

Background  

Physician practical support (e.g. setting goals, pro-active follow-up) and communicative support (e.g., empathic listening, eliciting preferences) have been hypothesized to influence diabetes outcomes.     

Validation of the medical outcomes study family and marital functioning measures in SLE patients in Singapore.

OBJECTIVE: To validate the Medical Outcomes Study Family and Marital Functioning Measures (FMM and MFM) in a multi-ethnic, urban Asian population in Singapore. METHODS: English speaking Chinese, Malay or Indian SLE patients (n=120) completed a self-administered questionnaire containing the FFM and MFM at baseline, after 2 weeks and after 6 months. Lupus activity, disease-related damage and quality of life were assessed using the British Isles Lupus Assessment Group (BILAG), Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) Damage Index and SF-36 Health Survey respectively. Scale psychometric properties were assessed through factor analysis, Cronbach's alpha, quantifying test-retest differences and known-groups construct validity. RESULTS: Factor analysis of scores obtained at baseline and after 6 months identified 3 factors corresponding to the FFM (1 factor) and the MFM (2 factors). Both scales showed acceptable internal consistency, with Cronbach's alpha of 0.95 for the FFM and 0.70 for the MFM. Mean (s.d.) test-retest differences were -0.31 (3.82) points for the FFM and -0.70 (4.26) points for the MFM. Eleven out of 13 a priori hypotheses relating both the FFM and MFM to demographic, disease and quality of life variables were confirmed, supporting the construct validity of these scales. CONCLUSION: The FFM and MFM are valid and reliable measures of family and marital functioning in a multi-ethnic cohort of Asian SLE patients in Singapore.     

The Rheumatology Attitudes Index and its helplessness subscale are valid and reliable measures of learned helplessness in Asian patients with systemic lupus erythematosus.

OBJECTIVE: To assess the internal consistency, reliability, and construct validity of the Rheumatology Attitudes Index (RAI) and its subscales in a cohort of Asian patients with systemic lupus erythematosus (SLE). METHODS: English speaking ethnic Chinese, Malay, or Indian patients with SLE (n = 120) seen at a rheumatology unit completed a questionnaire containing the RAI twice within a 2 week period. Lupus activity was assessed using the British Isles Lupus Activity Group (BILAG) score, disease related damage using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) damage index, and quality of life using the Medical Outcome Survey Short Form 36 Health Survey (SF-36). Factor analysis and Cronbach's alpha were used to study the psychometric properties of the RAI. The magnitude of test-retest differences was assessed using the method of Bland and Altman. Relationships between the RAI, its helplessness (HS) and internality (IS) subscales, and BILAG, SLICC/ACR damage index and SF-36 scores were studied using Spearman's rank correlation. RESULTS: Factor analysis (n = 105) identified 2 factors corresponding to the HS and IS subscales of the RAI. All scales showed acceptable internal consistency, with Cronbach's alpha of 0.64 for the HS, 0.77 for the IS, and 0.74 for the RAI. Mean (SD) test-retest differences were 0.85 (3.96) points for the HS (n = 86), 0.81 (4.44) points for the IS (n = 85), and 1.46 (7.88) points for the RAI (n = 74). Six of 10 hypotheses relating the RAI and HS to demographic, disease, and quality of life variables were confirmed, supporting the construct validity of these scales. CONCLUSION: The RAI and its helplessness subscale are valid and reliable measures of learned helplessness in a multiethnic cohort of Asian patients with SLE in Singapore.     

Lymphoepithelioma-Like Carcinoma of the Skin: An Exceedingly Rare Primary Skin Tumor

Primary lymphoepithelioma-like carcinoma of the skin (LE-lCS) is a very rare cutaneous malignancy of uncertain origin. The neoplasm reveals typical morphological similarity to undifferentiated nasopharyngeal carcinoma (lymphoepithelioma). This case report presents a 47-year-old man with a 5 mm erythematous papule on dorsal nose of six months duration. The patient underwent complete surgical excision and is disease free 7 months later.     

Autosomal recessive mutations in nuclear transport factor KPNA7 are associated with infantile spasms and cerebellar malformation

Nuclear import receptors of the KPNA family recognize the nuclear localization signal in proteins and together with importin-β mediate translocation into the nucleus. Accordingly, KPNA family members have a highly conserved architecture with domains that contact the nuclear localization signal and bind to importin-β. Here, we describe autosomal recessive mutations in KPNA7 found by whole exome sequencing in a sibling pair with severe developmental disability, infantile spasms, subsequent intractable epilepsy consistent with Lennox–Gastaut syndrome, partial agenesis of the corpus callosum, and cerebellar vermis hypoplasia. The mutations mapped to exon 7 in KPNA7 result in two amino-acid substitutions, Pro339Ala and Glu344Gln. On the basis of the crystal structure of the paralog KPNA2 bound to a bipartite nuclear localization signal from the retinoblastoma protein, the amino-acid substitutions in the affected subjects were predicted to occur within the seventh armadillo repeat that forms one of the two nuclear localization signal-binding sites in KPNA family members. Glu344 is conserved in all seven KPNA proteins, and we found that the Glu354Gln mutation in KPNA2 is sufficient to reduce binding to the retinoblastoma nuclear localization signal to approximately one-half that of wild-type protein. Our data show that compound heterozygous mutations in KPNA7 are associated with a human neurodevelopmental disease, and provide the first example of a human disease associated with mutation of a nuclear transport receptor.     

Functional absence of extraocular photoreception in hamster circadian rhythm entrainment.

The mammalian circadian pacemaker is entrainable by light via the retina. The putative role of extraocular light perception was investigated in blinded hamsters. These animals were shaved and exposed to a light-emitting pad for either 30 min or 3 h. The absence of any phase-shifting effects on wheel running activity rhythms indicates that extraocular light perception plays no functional role in photic entrainment of the circadian pacemaker in the hamster.