急性缺血性卒中影像学检查的建议——美国心脏协会的科学声明（中）

2．3核磁共振血管成像（MRA） 2．3．1背景和方法：在头部MRI检查中常结合MRA,用于急性卒中患者病情评估以指导治疗决策的制定^[19]。日前,有几种不同的MRA技术用于脑血管成像,包括二维时间飞跃（timeof-flight,TOF）序列、三维TOF序列、     

Update Experience of Surgery for Acute Limb Ischaemia in a District General Hospital – Are We Getting Any Better?

INTRODUCTION

The aims of this study were to audit results of a 10-year experience of surgery for acute limb ischaemia (ALI) in terms of limb salvage and mortality rates, and to compare results with a historical published series from our unit.

PATIENTS AND METHODS

All emergency operations performed during the period 1993–2003 were identified from theatre registers and patient notes reviewed to determine indications for, and outcome of, surgery. Data were compared to a similar cohort who underwent surgery from 1980 to 1990.

RESULTS

There was a 33% increase in workload from 87 to 116 patients between the two time periods. The number of patients with idiopathic ALI reduced (24% versus 4%; P < 0.05), and there were fewer smokers (71% versus 39%; P < 0.05) and a greater number of claudicants (17% versus 35%; P < 0.05) in those treated from 1993–2003. Latterly, more patients underwent pre-operative heparinisation (33% versus 80%; P < 0.05), received prophylactic antibiotics (14% versus 63%; P < 0.05), and had anaesthetic presence in theatre (46% versus 88%; P < 0.05). There was also a reduction in local anaesthetic procedures (80% versus 41%; P < 0.05). Despite increased pre-operative (15% versus 47%; P < 0.05) and on-table imaging (0% versus 16%; P < 0.05) technical success did not improve. Whilst complication rates were identical at 62%, there were fewer cardiovascular complications in the recent cohort. The 30-day mortality rate for embolectomy fell from 45% to 33%. Multivariate analysis revealed age > 70 years, prolonged symptom duration, ASA score ≥ III, lack of prophylactic antibiotics, absence of an anaesthetist, and operations performed under local anaesthetic to be associated with increased risk of mortality. Factors adversely affecting limb salvage included prolonged duration from symptom onset to operation, and a history of claudication or smoking.

CONCLUSIONS

Despite improvements in pre- and peri-operative management, arterial embolectomy/thrombectomy remains a procedure with a high morbidity and mortality. Further attempts to improve outcome must be directed at early diagnosis and referral as delay from symptom onset to surgery is a major determinant of outcome.     

Choosing event‐driven and daily HIV pre‐exposure prophylaxis – data from two European PrEP demonstration projects among men who have sex with men

IntroductionDaily and event‐driven PrEP are both efficacious in reducing the risk for HIV infection. However, the practice of event‐driven PrEP (edPrEP) is less well studied, in particular when provided as an alternative to daily PrEP. We studied regimen preferences and switches, and sexually transmitted infection (STI) incidence.MethodsWe analysed pooled data from two prospective cohort studies among MSM: Be‐PrEP‐ared, Belgium and AMPrEP, the Netherlands. In both projects, participants could choose between daily and edPrEP at three‐monthly study visits, when they were also screened for sexually transmitted infections including hepatitis C (HCV). We assessed the proportion choosing each regimen, and the determinants of choosing edPrEP at baseline. Additionally, we compared the incidence rates (IRs) of HCV, syphilis and chlamydia or gonorrhoea between regimens using Poisson regression. The study period was from 3 August 2015 until 24 September 2018.Results and discussionWe included 571 MSM, of whom 148 (25.9%) chose edPrEP at baseline. 31.7% of participants switched regimen at least once. After 28 months, 23.5% used edPrEP. Older participants (adjusted odds ratio (aOR) = 1.38 per 10 years, 95% confidence interval (CI) = 1.15 to 1.64) and those unemployed (aOR = 1.68, 95% CI = 1.03 to 1.75) were more likely to initially choose edPrEP. IR of HCV and syphilis did not differ between regimens, but the IR of chlamydia/gonorrhoea was higher among daily users (adjusted incidence rate ratio = 1.61, 95% CI = 1.35 to 1.94).ConclusionsA quarter of participants chose edPrEP at baseline and at 28 months this proportion was similar. Although the IR of HCV and syphilis were similar in the two regimens, the lower incidence of chlamydia and gonorrhoea among edPrEP users may suggest that less frequent STI testing of this group could be considered.     

A crucial role for TNF-α in mediating neutrophil influx induced by endogenously generated or exogenous chemokines,KC/CXCL1 and LIX/CXCL5

Background and purpose:

Chemokines orchestrate neutrophil recruitment to inflammatory foci. In the present study, we evaluated the participation of three chemokines, KC/CXCL1, MIP-2/CXCL2 and LIX/CXCL5, which are ligands for chemokine receptor 2 (CXCR2), in mediating neutrophil recruitment in immune inflammation induced by antigen in immunized mice.

Experimental approach:

Neutrophil recruitment was assessed in immunized mice challenged with methylated bovine serum albumin, KC/CXCL1, LIX/CXCL5 or tumour necrosis factor (TNF)-α. Cytokine and chemokine levels were determined in peritoneal exudates and in supernatants of macrophages and mast cells by elisa. CXCR2 and intercellular adhesion molecule 1 (ICAM-1) expression was determined using immunohistochemistry and confocal microscopy.

Key results:

Antigen challenge induced dose- and time-dependent neutrophil recruitment and production of KC/CXCL1, LIX/CXCL5 and TNF-α, but not MIP-2/CXCL2, in peritoneal exudates. Neutrophil recruitment was inhibited by treatment with reparixin (CXCR1/2 antagonist), anti-KC/CXCL1, anti-LIX/CXCL5 or anti-TNF-α antibodies and in tumour necrosis factor receptor 1-deficient mice. Intraperitoneal injection of KC/CXCL1 and LIX/CXCL5 induced dose- and time-dependent neutrophil recruitment and TNF-α production, which were inhibited by reparixin or anti-TNF-α treatment. Macrophages and mast cells expressed CXCR2 receptors. Increased macrophage numbers enhanced, while cromolyn sodium (mast cell stabilizer) diminished, LIX/CXCL5-induced neutrophil recruitment. Macrophages and mast cells from immunized mice produced TNF-α upon LIX/CXCL5 stimulation. Methylated bovine serum albumin induced expression of ICAM-1 on mesenteric vascular endothelium, which was inhibited by anti-TNF-α or anti-LIX/CXCL5.

Conclusion and implications:

Following antigen challenge, CXCR2 ligands are produced and act on macrophages and mast cells triggering the production of TNF-α, which synergistically contribute to neutrophil recruitment through induction of the expression of ICAM-1.     

Surface Mucin-1 does not play a role in dendritic cell migration

Mucin-1 (MUC1) is a transmembrane glycoprotein that is upregulated upon maturation of dendritic cells (DC) in vitro or in vivo. One of the proposed functions of surface expressed MUC1 is its involvement in migration of cells. We hypothesized that MUC1 is involved in DC migration since mature DC (mDC) are highly migratory cells and MUC1 is upregulated on the surface of DC upon maturation. In this study we cultured DC using two maturation cocktails, one cocktail containing IL-4, GM-CSF, TNFalpha, PGE2, IL-1 beta and IL-6 (TP1,6-DC) and the other IL-13, GM-CSF, Ribomunyl and IFN-gamma (RI-DC). Both maturation cocktails render DC with a similar surface phenotype including CCR7 expression, but only the former induces a migratory capacity of DC to a CCL19 gradient. To analyze the role of surface-expression of MUC1 on TP1,6-DC, that are capable of migration, expression of MUC1 was prevented by adding an anti-MUC1 antibody (Ab) during the maturation process. Compared with matured DC in the absence of the Ab, no difference was observed in chemokine-induced migratory behaviour between the MUC1+ and MUC1- DC populations in a standard Transwell chemotaxis assay, nor in organotypic cultures. Our data clearly demonstrate that surface MUC1 on DC does not influence intrinsic cell-motility, nor is it involved in cell-cell and cell-matrix dependent migration.     

Acute generalized exanthematous pustulosis due to thallium

Acute generalized exanthematous pustulosis (AGEP) is characterized clinically by fever, pruritus and acute pustular eruption. Usually a drug is found to be the responsible agent. We present a patient who experienced an acute generalized exanthematous pustulosis due to radioactive thallium. The eruption cleared rapidly after discontinuation of the drug and systemic corticosteroid therapy.     

The breast cancer resistance protein transporter ABCG2 is expressed in the human kidney proximal tubule apical membrane

The Breast Cancer Resistance Protein (BCRP/ABCG2) is a transporter restricting absorption and enhancing excretion of many compounds including anticancer drugs. This transporter is highly expressed in many tissues; however, in human kidney, only the mRNA was found in contrast to the mouse kidney, where the transporter is abundant. In bcrp/abcg2((-/-)) mice, the expression of two sterol transporter genes, abcg5 and abcg8, was strongly increased in the kidney, perhaps as a compensatory mechanism to upregulate efflux. We found using immunohistochemical analysis clear localization of BCRP/ABCG2 to the proximal tubule brush border membrane of the human kidney comparable to that of other ABC transporters such as P-glycoprotein/ABCB1, MRP2/ABCC2, and MRP4/ABCC4. Hoechst 33342 dye efflux from primary human proximal tubule cells was significantly reduced by the BCRP/ABCG2 inhibitors fumitremorgin C and nelfinavir. Our study shows that in addition to other apical ABC transporters, BCRP/ABCG2 may be important in renal drug excretion.     

Determinants of red blood cell deformability in relation to cell age

Abstract: Red blood cell (RBC) deformability was determined with an ektacytometer in fractions separated on the basis of differences in cell volume or density. Deformability was measured with ektacytometry (rpm-scan and osmo-scan). We studied three groups of RBC fractions: 1. By counterflow centrifugation we obtained fractions of different cell age which showed a slight decrease in mean corpuscular haemoglobin concentration (MCHC) and an increase in surface-to-volume (S/V) ratio in fractions with older cells. 2. By Percoll fractionation fractions were obtained which showed a pronounced increase in (MCHC) but no change in S/V ratio. 3. By a combination of both fractionation techniques, fractions were obtained which showed an increased MCHC and an increase in S/V ratio. Deformability in group 1,2 and 3 showed respectively no change, a moderate decrease and a pronounced decrease in fractions of older cells. A decline in deformability occurs during the aging process of the red blood cell. This decline in deformability in old red cells is greater than originally thought. This decline is the result of an increase in haemoglobin concentration and a second factor, probably a decrease in membrane elasticity.