马兜铃酸的倍半萜的酯类化合物VI.绵毛马兜铃中马兜铃酸萜酯I的结构鉴定

从绵毛马兜铃(Aristolocha mannisima Hance)中分得一个马兜铃酸倍半萜的酯类化合物,经红外、紫外、高分辩质谱和多种一维和二维核磁共振谱鉴定,确定了其骨架结构及顺反构型,命名为马兜铃酸萜酯I。     

Clinical multimorbidity and physical function in older adults: a record and health status linkage study in general practice

BACKGROUND: Multiple chronic conditions occurring in the same individual are associated with adverse health outcomes. In family practice, individuals are seen who, over time, may experience many different symptoms, illnesses and chronic diseases. Measures for defining multimorbidity, which incorporate the diverse range of health problems seen in population-based family practice, remain to be developed. We have investigated whether routinely collected consultation data could be used as the basis for a simple classification of multimorbidity that reflects an individual's overall health status. METHODS: Morbidity consultation data for 9,439 English patients aged 50 years and over in an 18-month time period were linked to their self-reported physical health status measured by Short-Form 12 at the end point. Associations between physical function and all-cause multimorbidity counts were estimated relative to single morbidity only, and between physical function and morbidity severity (185 morbidities categorized on four ordinal scales of severity) relative to persons who had not consulted about any of the 185. RESULTS: In the 18-month period, 19% had consulted for a single morbidity and 23% for six or more (a high multimorbidity count). An estimated 24% of poor physical function in the family practice consulting population may be attributable to high multimorbidity. There was an increasing strength of association between poor physical function and increasing severity of multimorbidity on all four severity scales. Estimated associations (adjusted odds ratios) of the most severe morbidity categories with poor physical function were, for each of the four scales, respectively, 5.6 for chronicity [95% confidence interval (CI) 4.4-7.1], 7.0 for time course (4.5-10.6) and 3.6 for health care use (2.0-6.6) and for patient impact (6.7; 5.2-8.8). CONCLUSIONS: Multimorbidity defined by using routinely collected family practice consultation data and classified by count and by severity was associated with poorer physical function. This approach offers the potential for systematic use of routine records to classify multimorbidity and to identify groups with high likelihood of poor physical status for needs assessment and targeted intervention.     

Preclinical to Clinical Translation of CNS Transporter Occupancy of TD-9855, a Novel Norepinephrine and Serotonin Reuptake Inhibitor

Background:

Monoamine reuptake inhibitors exhibit unique clinical profiles that reflect distinct engagement of the central nervous system (CNS) transporters.

Methods:

We used a translational strategy, including rodent pharmacokinetic/pharmacodynamic modeling and positron emission tomography (PET) imaging in humans, to establish the transporter profile of TD-9855, a novel norepinephrine and serotonin reuptake inhibitor.

Results:

TD-9855 was a potent inhibitor of norepinephrine (NE) and serotonin 5-HT uptake in vitro with an inhibitory selectivity of 4- to 10-fold for NE at human and rat transporters. TD-9855 engaged norepinephrine transporters (NET) and serotonin transporters (SERT) in rat spinal cord, with a plasma EC₅₀ of 11.7ng/mL and 50.8ng/mL, respectively, consistent with modest selectivity for NET in vivo.Accounting for species differences in protein binding, the projected human NET and SERT plasma EC₅₀ values were 5.5ng/mL and 23.9ng/mL, respectively. A single-dose, open-label PET study (4–20mg TD-9855, oral) was conducted in eight healthy males using the radiotracers [¹¹C]-3-amino-4- [2-[(di(methyl)amino)methyl]phenyl]sulfanylbenzonitrile for SERT and [¹¹C]-(S,S)-methylreboxetine for NET. The long pharmacokinetic half-life (30–40h) of TD-9855 allowed for sequential assessment of SERT and NET occupancy in the same subject. The plasma EC₅₀ for NET was estimated to be 1.21ng/mL, and at doses of greater than 4mg the projected steady-state NET occupancy is high (>75%). After a single oral dose of 20mg, SERT occupancy was 25 (±8)% at a plasma level of 6.35ng/mL.

Conclusions:

These data establish the CNS penetration and transporter profile of TD-9855 and inform the selection of potential doses for future clinical evaluation.     

Flexible tantalum stents implanted in aortas and iliac arteries: effects in normal canines

Vascular endoprostheses made of knitted tantalum wire and expanded over angioplasty balloons were placed into aortas or iliac arteries of 14 normal dogs. Twelve stents were placed into the infrarenal abdominal aorta and two stents in the left common iliac arteries by the left carotid artery approach. To firmly expand the stent against the vascular wall, nominal stent sizes 0.5-1.0 mm larger than the measured arterial diameter were required. Arteriography performed at specified follow-up intervals showed no evidence of thrombi or emboli; all side branches (lumbar arteries) covered by the stents remained patent. Vascular diameter decreased minimally at 8 and 26 weeks, associated with histopathologic evidence of neointimal buildup. This buildup was highest at 8 weeks (mean, 313 microns) and was slightly less at 26 weeks (mean, 223 microns). Almost complete coverage by endothelium was seen as early as 3 weeks. It is concluded that the flexible tantalum wire stents are well tolerated by the arterial wall and become quickly endothelialized. No excessive neointimal buildup was observed during the 6-month study.     

Consensus of microbiology reporting of ear swab results to primary care clinicians in patients with otitis externa

Otitis externa is a ubiquitous inflammatory disease; although it arises most commonly from an infection, there is no consensus in the UK for the reporting of ear swab culture results. This study aims to review current microbiology laboratory reporting of ear swab specimens to primary care and reach an evidence-based consensus for a reporting policy. Fifty consecutive ear swab reports were reviewed from each of 12 laboratories in the South West region to determine and discuss reporting practice. The Health Protection Agency (HPA) GP Microbiology Laboratory Use Group reviewed the underlying evidence and worked towards a consensus of expert microbiology opinion for laboratory reporting of ear swab results using a modified version of the Delphi technique. A total of 487 reports from primary care were reviewed (54% female; 46% male). Cultures most commonly yielded Pseudomonas species (36%), Staphylococcus species (21%), Streptococcus species (15%) and fungi (11%). Five reporting policies were agreed: Policy 1: Common pathogens such as group A beta-haemolytic streptococci, Streptococcus pneumoniae, Staphylococcus aureus - Always reported by name with antibiotic susceptibilities. Policy 2: Pseudomonas species - Always reported, but antibiotic susceptibilities only reported in severe disease. Policy 3: Aspergillus, Candida, coliforms and Proteus species, as well as non-group A streptococci and anaerobes - Only reported if moderate numbers of colonies and it is the predominant organism present; if appropriate report antibiotic susceptibilities. Policy 4: Coagulase-negative staphylococci, diphtheroids and enterococci - Not reported by name; generic terms used and antibiotic susceptibilities not reported. Policy 5: When antibiotic susceptibilities reported these must include susceptibility to a topical antibiotic. It is suggested that laboratories should consider adopting this evidence-based reporting consensus for ear swab culture results from primary care patients with otitis externa.     

Spontaneous gastric rupture in the newborn: a clinical review of nineteen cases.

The term "spontaneous gastric rupture" is used to describe our cases of neonatal gastric perforation. Nineteen such neonates are reviewed. Current opinions regarding the possible etiology is included in the discussion. Neonatal asphyxia was the most commonly seen predisposing cause in our series (63%). Roentgenograms of the abdomen are most helpful in making a positive diagnosis. Surgical repair is the treatment of choice. All the surviving patients in our series underwent surgical repair. The need for gastrostomy during surgery should be individualized. The mortality was 27% in the cases operated since 1970; a significant improvement as compared to a mortality rate of 62% for the cases operated before 1970.