Blood pressure control in the Hypertension in the Very Elderly Trial (HYVET)

To report blood pressure control in the Hypertension in the Very Elderly Trial, a placebo-controlled trial of hypertensive (systolic blood pressure (SBP) 160-199?mm?Hg, diastolic blood pressure (DBP) <110?mm?Hg) participants over the age of 80 years, given treatment in three steps: indapamide slow release 1.5?mg alone, indapamide plus 2?mg perindopril and indapamide plus 4?mg perindopril. The difference in control between participants with combined systolic and diastolic hypertension (SDH, DBP90?mm?Hg) and those with isolated systolic hypertension (ISH, DBP<90?mm?Hg) is determined together with the effects of increments in the treatment regimen. At 2 years, the active treatment lowered blood pressure by 16.5/6.9?mm?Hg more than that on placebo in participants with SDH and by 19.3/4.8?mm?Hg more in those with ISH. The 2-year falls in pressure on placebo alone were 13.2/8.5?mm?Hg in SDH and 8.2/1.5?mm?Hg in ISH participants. With full titration of active treatment, 62% of SDH participants achieved goal SBP (<150?mm?Hg) by 2 years and 71% of those with ISH. The corresponding results for DBP control (<80?mm?Hg) were 40 and 78%. The addition of active perindopril 2?mg roughly doubled the percentage controlled, as did increasing to 4 from 2?mg. Blood pressure control was good with ISH and better than with SDH. The fall in SBP accounted for the observed 30% reduction in strokes, but the 21% reduction in total mortality and 64% reduction in heart failure were greater than predicted.     

Enhanced Bone Regeneration Using Porcine Small Intestinal Submucosa

Small instestinal submucosa (SIS) is an easily produced material that has been used experimentally for tissue engineering. To evaluate the ability of SIS to facilitate bone growth within a long-bone defect, a segment of the radius was surgically removed in adult, female Sprague-Dawley rats. The defect was either left unfilled or implanted with SIS, demineralized cortical bone (DMCB), or ovalbumin. The defect was evaluated radiographically and histologically after 3, 6, 12, and 24 weeks. Tissue remodeling within the defect was evident by week 3 in SIS- and DMCB-treated rats. Filling was characterized initially by infiltration of mononuclear cells and extracellular material in SIS-implanted rats and multifocal remodeling bone particles and cartilage formation in DMCB implanted rats. Cartilage was observed as early as 3 weeks and bone as early as 6 weeks in SIS-implanted rats. Filling of the defect arose from multiple foci in DMCB-implanted rats, but was contiguous with and parallel to the ulnar shaft in SIS-implanted rats, suggesting that defect repair by SIS may be conductive rather than inductive. Rats in which the defect was left unfilled demonstrated slow but progressive filling of the defect, characterized by mononuclear cell infiltrates and fibrous extracellular material. In summary, SIS facilitated rapid filling of a longbone defect. These results suggest that SIS may be useful as a bone repair material.     

The Quality of Life of Family Caregivers of Eating Disorder Patients

Having a relative with an eating disorder (ED) affects the life of family caregivers and may thus affect their quality of life. To study this aspect, 40 caregivers of ED patients filled out a health-related quality of life questionnaire (Short Form-36) and a questionnaire on the impact of the ED on various areas of life domains, and on the relationship with the ED patient and the need for professional support. Quality of life of caregivers was worse than in a normal reference group. Specifically, mental health, vitality and emotional role functioning were reported to be most impaired. ED appeared to affect families’ lives substantially. In response to the ED, caregivers felt anxious, powerless, sad, or desperate. The relationship of the caregiver with the ED patient had also changed. Caregivers were more worried, lost their trust, and reported more conflicts. Seventy five percent welcomed professional support. Caregivers need practical advice, information on ED, and emotional support. Quality of life of caregivers should be addressed in the treatment of ED.     

Surrogate markers for cerebral blood flow correlate with [18F]‐fallypride binding potential at dopamine D2/3 receptors in human striatum

Positron emission tomography (PET) with the high affinity dopamine D_2/3 receptor ligand [¹⁸F]‐fallypride affords estimates of the binding potential (BP_ND) in extra‐striatal regions of low receptor abundance, but the sufficient recording time for accurate measurements in striatum has been called into question. We have earlier argued that transient equilibrium measurements are obtained in striatum with [¹⁸F]‐fallypride PET recordings of 3 h duration, which may be the practical limit for clinical investigations without interrupted scanning. However, the high extraction fraction of [¹⁸F]‐fallypride predicts flow‐dependence of tracer delivery to brain, which may be a source of variance of the apparent BP_ND in regions of high binding. To test this prediction, we conducted a retrospective analysis of [¹⁸F]‐fallypride PET data from a group of 50 healthy volunteers (age 18–58 years [mean ± SD: 32.6 ± 10.6), who had participated in clinical studies without arterial input measurements. We used the initial 120‐s integral (AUC) of the venous confluence (VC) as a surrogate marker for cerebral blood flow (CBF) and tested for correlations between regional estimates of BP_ND calculated by the simplified reference tissue model (SRTM) and the individual VC‐AUC. The magnitude of BP_ND in a high binding region (putamen), but not in a low binding region (thalamus) correlated positively with VC‐AUC, suggesting that approximately 9% of the variance in the [¹⁸F]‐fallypride BP_ND in putamen can be attributed to individual differences in this surrogate marker for CBF, a contribution equal in magnitude to the effects of age on BP_ND in putamen of the present healthy control group. Synapse, 2013. © 2012 Wiley Periodicals, Inc.     

Perceived Value of Teaching and Learning Curriculum Programs Among Pharmacy Practice Department Chairs

Objective. To determine the perceived value that pharmacy practice department chairs ascribe to pharmacy faculty candidates having completed a teaching and learning curriculum (TLC) program and related activities.Methods. An 18-item survey instrument was created that was intended to capture the overall impressions of pharmacy practice chairs regarding the value of TLC programs, relative importance compared to other accomplishments (eg, residency completion, board certification), and importance of specific activities. Following pilot testing and establishment of intra-rater reliability, invitations to complete the electronic survey instrument were sent to pharmacy practice chairs (or their equivalent) at accredited Doctor of Pharmacy (PharmD) programs in the United States.Results. Of the 127 pharmacy practice chairs invited, 53 completed the survey (response rate of 41.7%). The majority of respondents held a PharmD degree (90.6%), had been in their role of chair for zero to five years (60.4%), and represented a private institution (54.7%). The majority of respondents who answered the question (32 of 49) felt it was very important or important (16.3% and 49.0%, respectively) that teaching experiences be completed within a formal teaching and learning curriculum program. These programs were believed to be most important for candidates with less than five years of professional experience. Teaching and learning curriculum programs were not deemed to be more important than other accomplishments by most responders. The perceived most important TLC program activities were instruction on didactic and experiential teaching strategies, and experience developing learning objectives, developing examination items, evaluating examination results, and facilitating case conferences or practice laboratory activities.Conclusion. Teaching and learning curriculum programs may provide the foundational experiences needed for pharmacy graduates to stand out among other candidates, although department chairs’ perceptions of the value of teaching and learning curriculum experiences varied.     

亚麻子水提液对DPP-4及α-葡萄糖苷酶活性抑制实验研究

目的通过观察亚麻子水提液对二肽基肽酶-4（DPP-4）、α-葡萄糖苷酶抑制作用,为该药防治糖尿病提供实验依据。方法①以DPP-4酶、缓冲液、底物建立DPP-4抑制剂的体外筛选体系,对亚麻子水提液进行抑制实验,采用发色底物法测定吸光度（OD）,计算DPP-4抑制率及IC50值;②以蔗糖为底物建立α-葡萄糖苷酶活性抑制模型,采用葡萄糖氧化酶法测定亚麻子水提液对α-葡萄糖苷酶的抑制作用,计算其抑制率和IC50值。结果①亚麻子具有轻度DPP-4抑制作用,其IC50值738.20mg/L;②亚麻子具有α-葡萄糖苷酶抑制作用,其IC50值为365.9mg/mL。结论亚麻子水提液可一定程度地抑制DPP-4及α-葡萄糖苷酶活性。     

广州市荔湾区青少年脊柱侧凸患病率的调查研究

目的了解广州市荔湾区青少年脊柱侧凸的患病率。方法 2011年7月~2012年1月对荔湾区8351名7~15岁在校中小学生进行了脊柱侧凸普查,应用脊柱侧凸两检法（体检、X线照片）,体检阳性或可疑阳性者到医院照脊柱全长正侧位X片,采用Cobb法测量,Cobb角≥10°诊断为脊柱侧凸。结果一检阳性结果 175名（2.1%）,二检阳性为85名（1.02%）,男性31名,女性54名,男∶女患病率比为1∶1.76,其中特发性脊柱侧凸81名,占95.3%,先天性侧凸3名,神经肌肉源性1名。结论荔湾区中小学生脊柱侧凸发病率为1.02%,通过普查,可以早发现、早诊断青少年脊柱侧凸,及时选择适当方法进行治疗。     

von Willebrand factor released from Weibel-Palade bodies binds more avidly to extracellular matrix than that secreted constitutively

Large multimers of von Willebrand factor (vWf) are released from the Weibel-Palade bodies of cultured endothelial cells following treatment with a secretagogue (Sporn et al, Cell 46:185, 1986). These multimers were shown by immunofluorescent staining to bind more extensively to the extracellular matrix of human foreskin fibroblasts than constitutively secreted vWf, which is composed predominantly of dimeric molecules. Increased binding of A23187-released vWf was not due to another component present in the releasate, since releasate from which vWf was adsorbed, when added together with constitutively secreted vWf, did not promote binding. When iodinated plasma vWf was overlaid onto the fibroblasts, the large forms bound preferentially to the matrix. These results indicated that the enhanced binding of the vWf released from the Weibel-Palade bodies was likely due to its large multimeric size. It appears that multivalency is an important component of vWf interaction with the extracellular matrix, just as has been shown for vWf interaction with platelets. The pool of vWf contained within the Weibel-Palade bodies, therefore, is not only especially suited for platelet binding, but also for interaction with the extracellular matrix.     

Analysis of interleukin-4 and interleukin-10 and their association with the lymphocytic infiltrate in the small intestine of patients with coeliac disease.

BACKGROUND: Concentrations of pro-inflammatory cytokines are raised in the small intestine of patients with coeliac disease after ingestion of gluten but there are equivalent data on interleukin-4 (IL-4) and interleukin-10 (IL-10) producing cells. These cytokines are known to exert important regulatory effects on pro-inflammatory cytokine production from lymphocytes and macrophages. AIMS: To investigate whether there is a primary deficiency of IL-4 and IL-10 producing cells and their site of production in the small intestine of patients with coeliac disease in relation to the changes in inflammatory cell infiltrate. PATIENTS: Jejunal biopsy specimens from patients with coeliac disease (11 untreated, 10 treated) and nine disease controls were studied. METHODS: Immunohistochemical staining of sections for IL-4 and IL-10 cytokines and the cell phenotypic markers CD3 (T lymphocytes) and CD45 (total inflammatory cell infiltrate) was carried out using monoclonal antibodies. Expression of IL-4 and IL-10 messenger RNA was detected by in situ hybridisation with oligonucleotide probe cocktails for each cytokine. RESULTS: IL-4 and IL-10 mRNA and protein were detected in the lamina propria of treated and untreated coeliac patients and disease controls but not in the epithelium. A significant increase in the number of CD45 (p < 0.005) and CD3 (p < 0.05) positive cells was found in the lamina propria of patients with untreated coeliac disease compared with treated coeliac patients and disease controls but there were no differences in IL-4 or IL-10 between these groups with either method. CONCLUSIONS: There is no primary deficiency of IL-4 and IL-10 producing cells in the small intestine of patients with coeliac disease. Detectable concentrations of IL-4 and IL-10 were found in control patients which suggests that these cytokines are involved in normal mucosal immunoregulation. The increased number of T lymphocytes but not IL-4 or IL-10 producing cells in the lamina propria of patients with untreated than in those with treated disease suggests not only that the lamina propria is the major mucosal compartment for cytokine production but that newly recruited mucosal T lymphocytes are directed to a predominant Th1 and not a Th2 cytokine response in coeliac patients on a diet containing gluten.