Ultrasound-determined fetal subcutaneous tissue thickness for a birthweight prediction model

AIM: The aim of this study was to explore a birthweight prediction model using ultrasound determined tissue thickness (SCTT) parameters. METHODS: We measured routine ultrasonographic biometric parameters and in addition, fetal SCTT in 201 healthy singleton pregnancies. Mid-arm fat and lean mass, mid-thigh fat and lean mass, subscapular fat mass and abdominal fat mass (AFM) were measured in order to calculate a birthweight prediction model. Ultrasound measurements were analyzed using an 'anovarepeated measures model'. The growth rate (beta-slope) of the selected parameters was computed and the correlation coefficient with the birthweight and the Kendall rank correlation tau, were calculated. RESULTS: From the ultrasound determined SCTT parameters, only abdominal circumference (AC), AFM, and MTLM showed a statistically significant trend. The beta-slope of mid-thigh lean mass was excluded since it exhibited significant correlation with the beta-slope of AFM. The final regression model could be calculated as: birthweight (gr.) = intercept +alpha(1)(AFM beta-slope) + alpha(2)(AC beta-slope), where alpha(1), alpha(2) represent regression coefficients. CONCLUSIONS: We provide a graphical birthweight prediction model for clinical practice using conventional and specific ultrasound measurements of fetal subcutaneous tissue thickness. This model is based upon an overall analysis of the ultrasound estimated body components.     

毛囊真皮鞘细胞中过表达Noggin对皮肤及毛囊生长的作用

背景:Noggin蛋白是一个抑制BMP信号通路的重要分子,可以与BMP2/4结合形成复合物,从而阻断BMP信号,影响生物有机体的正常发育过程。研究认为真皮鞘细胞是一类能够长期自我更新的真皮干细胞,参与毛囊再生过程中真皮毛乳头和真皮鞘的形成。在毛囊发育过程中,真皮毛乳头中Noggin参与毛囊的起始,Noggin的缺失会导致毛囊数量的减少和毛囊生长缓慢,但人们对于Noggin蛋白在毛囊真皮鞘中的作用所知甚少。目的:研究Noggin蛋白在毛囊真皮鞘中的生物学功能。方法:利用真皮鞘特异的αSMA-Cre ERT2工具鼠在真皮鞘中特异过表达Noggin蛋白,分别在出生后8,9 d对实验组αSMA-CreER;pMES-Noggin小鼠和对照组αSMA-CreER小鼠注射4-羟基他莫昔芬,在出生后21,23,28 d获取皮肤组织,苏木精-伊红染色观察毛囊生长情况和皮下脂肪层厚度,免疫组化染色分析表型。结果与结论:通过苏木精-伊红染色结果发现毛囊生长并没有受到影响,但毛囊皮下脂肪组织生长发育受到严重影响,小鼠皮下脂肪层变薄。免疫组化结果说明BMP信号降低可能是导致毛囊脂肪层变薄的原因。这一发现拓展了人们对于真皮鞘细胞和Noggin蛋白的认识,也为人们更加准确理解毛囊再生和组织生长机制提供了重要依据。     

In vitro biosynthesis of plasma proteins under ischemic conditions of closed-circuit perfusion of healthy and intoxicated rabbit liver

We are elaborating on the kinetics and mechanisms of septic rabbit liver to de novo biosynthesize acute-phase response (APR) proteins under in vitro conditions of deepening ischemia in reference to their in vivo prevalence in serum and cerebrospinal fluids (CSF) collected at predetermined times. The significance of the data is interpreted as relevant to grafting cadaveric liver into end-stage liver diseased patients and APR-induced ischemic heart diseases (IHD). Hepatic APR was induced by CCl(4)-intubation, and the administration of cholera toxin (CT) or scorpion venom (SV), or both, to rabbits. Hepatic functional efficiency, in terms of biosynthesis of APR proteins in closed circuit perfusion of the isolated intoxicated liver with oxygenated saline or L-15 media paralleled the two-dimensional immunoelectrophoresis (2D-IEP) spectrum of APR serum proteins at time of liver isolation. We are suggesting: (a) in vitro biosynthesis of plasma proteins by isolated perfused liver is the result of in vivo decoded and retained APR inflammatory signals; and (b) decoded inflammatory signals are expressed not withstanding the perfusate's organic composition. Furthermore, 90 min of ischemic perfusion in saline or L-15 medium precipitated mitochondrial aberrations which resulted in further deterioration of de novo biosynthesis of APR plasma proteins. Regardless of the nature of the inflammatory stimuli, mitochondrial aberrations rendered the perfused organ a biologically inert tissue mass that was incapable of resuming biological function upon perfusion with oxygenated L-15 medium. This is most likely due to ischemia-induced irreversible hepatic necrosis. Thus, in vitro aberrations of mitochondrial function(s) critically limit the capability of the isolated liver to resume its organic function to sustain biosynthesis of de novo plasma proteins. Extrapolation of these results to the surgical management of end-stage liver diseases points to the importance of the status and the handling protocol(s) of the cadaver donor liver prior to successful grafting. We conclude that although histology of a cadaver liver may reveal well-preserved hepatic cellular organelles with at least minimal intra- and intercellular communication required for viable hepatic function, we deem it essential to further define acceptable minimal capabilities to de novo biosynthesize plasma proteins by a cadaver liver as a measure of its functional viability and suitability for transplantation. Ultimately, this measure may improve the success of liver transplants with minimal surgical and drug interventions.     

皮下注射福尔马林对猫初级传入单位反应的影响──电生理学研究

作者以前的研究曾显示：皮下注射福尔马林引起的背角伤害感受性单位长时程反应主要取决于周围传入。当阻断坐骨神经时可以使广动力型神经元的这种反应被完全抑制。为了进一步阐明福尔马林引起的伤害性感受的周围机制，本文用细胞外记录技术记录了在乌拉坦—氯醛糖麻醉下猫的Ｌ７背根神经节的初级传入单位．与背角完全一致，皮下注射福尔马林引起非伤害性感受性单位短时程的峰放电增加，例如Ａβ－毛囊型，Ａβ－快适应型，Ａβ－慢适应Ⅰ型，Ａβ－慢适应Ⅱ型，Ａδ－Ｄ毛发型以及Ｃ－低阈值机械感受性单位等，其放电均低于１０分钟；而使伤害感受性单位的放电有长时程的增加，例如Ａδ－高阈值机械伤害感受性单位放电为３０～７０分。令人感到意外的是，在单位放电终止时，检测实验中所有初级传入单位对其相应注射部位的任何机械刺激都失去反应．将此结果与以前的实验结果一起分析时可以得出结论；福尔马林引起的中枢神经改变主要取决于上传的周围传入影响，而福尔马林引起的背角单位放电的时程，则取决于外周传入纤维的分布．本文还提出和讨论了关于福尔马林引起伤害性感受机制的新见解。     

Multiple-allergen and single-allergen immunotherapy strategies in polysensitized patients: looking at the published evidence

In allergen immunotherapy there is debate as to whether polysensitized patients are best treated with many allergens simultaneously (chosen according to the sensitization profile, a predominantly North American approach) or a single allergen (chosen according to the most clinically problematic allergy, a predominantly European approach). In patients seeking treatment for moderate-to-severe respiratory allergies, polysensitization is more prevalent (range, 50% to 80%) than monosensitization in both the United States and Europe. Safe, effective, single-allergen preparations will most likely have been tested in polysensitized patients. In robust, large-scale clinical trials of grass pollen sublingual tablets, polysensitized patients benefited at least as much from allergen immunotherapy as monosensitized patients. A recent review of multiallergen immunotherapy concluded that simultaneous delivery of multiple unrelated allergens can be clinically effective but that there was a need for additional investigation of therapy with more than 2 allergen extracts (particularly in sublingual allergen immunotherapy). More work is also required to determine whether single-allergen and multiallergen immunotherapy protocols elicit distinct immune responses in monosensitized and polysensitized patients. Sublingual and subcutaneous multiallergen immunotherapy in polysensitized patients requires more supporting data to validate its efficacy in practice.     

Evaluation of correlation between dose and clinical outcomes in subcutaneous immunoglobulin replacement therapy

The importance of serum immunoglobulin (Ig)G concentration in IgG replacement therapy for primary immunodeficiency diseases is established in certain settings. Generally, IgG is infused via the intravenous (IVIG) or subcutaneous (SCIG) route. For IVIG infusion, published data demonstrate that higher IgG doses and trough levels provide patients with improved protection from infection. The same conclusions are not yet accepted for SCIG; data from two recent Phase III studies and a recent post-hoc analysis, however, suggest the same correlation between higher SCIG dose and serum IgG concentration and decreased incidence of infection seen with IVIG. Other measures of clinical efficacy have not been considered similarly. Thus, combined analyses of these and other published SCIG studies were performed; a full comparison of the 13 studies was, however, limited by non-standardized definitions and reporting. Despite these limitations, our analyses indicate that certain clinical outcomes improve at higher SCIG doses and associated higher serum IgG concentrations, and suggest that there might be opportunity to improve patient outcomes via SCIG dose adjustment.     

腹膜后腔镜手术并发高二氧化碳血症的临床观察

目的观察腹膜后腔镜手术高二氧化碳血症的发生情况,分析其相关因素,为麻醉管理提供指导。方法选取择期腹膜后腔镜手术患者40例,观测并记录气腹前（T0）、气腹后30min（T1）、气腹后60min（T2）、气腹后90min（T3）、停气腹后30min（T4）各时点的心率（HR）、收缩压（SBP）、舒张压（DBP）、平均动脉压（MAP）、呼气末二氧化碳分压（PETCO2）、血氧饱和度（SpO2）;并同时行动脉血气分析,观察PH值、动脉血氧分压（PaO2）和动脉血二氧化碳分压（PaCO2）的变化;如患者合并皮下气肿,对其严重程度进行分级。结果全手术过程中所有患者的PaO2均〉100mmHg,SpO2均为100%,患者的HR、SBP、DBP和MAP基本平稳。与T0相比,T1、T2、T3患者PaCO2和PETCO2呈进行性升高,pH明显降低（P〈0.05）,T1、T2、T3高二氧化碳血症（PaCO2〉50mmHg）发生率分别为10%、41%、75%;30例发生皮下气肿,其中轻度13例、中度12例、重度5例,5例重度皮气肿患者PaCO2最高超过80mmHg,PETCO2最高超过50mmHg;另有1例术中出现气胸。结论腹膜后腔镜手术易发生高二氧化碳血症,气腹时间、皮下气肿严重程度等都为相关因素,提示麻醉期间应警惕高二氧化碳血症,以早期发现、及时处理。     

Rapid subcutaneous immunoglobulin administration every second week results in high and stable serum immunoglobulin G levels in patients with primary antibody deficiencies

Subcutaneous immunoglobulin G (SCIG) infusions as life-long replacement therapy in patients with primary antibody deficiences (PAD) is being applied increasingly. However, only a few published pharmacokinetic studies are available for this route of administration. Therefore, the pharmacokinetics of a 16% immunoglobulin G (IgG) preparation intended for subcutaneous use were investigated in patients with common variable immunodeficiency and X-linked agammaglobulinaemia. SCIG infusions (200 mg/kg body weight) were administered to 12 adult patients every 14 days for 24 weeks (total of 144 infusions). Pharmacokinetic parameters were determined based on serum IgG trough levels and antibody levels against tetanus. The median half-life of the total serum IgG and for the tetanus antibodies was 40.6 and 23.3 days respectively. Median in vivo recovery of serum IgG and tetanus immunoglobulins were 36% and 46% respectively. Median, preinfusion serum IgG trough levels per patient were high without major variations between infusions and ranged from 7.24 to 7.86 g/l. Safety, in terms of adverse events including systemic adverse reactions and local tissue reactions at infusions sites, was monitored throughout the study. Six mild, local tissue reactions were observed during the study in one patient. No systemic adverse reactions related to the study drug were observed and no serious other adverse event occurred during the study. It is concluded that the bi-weekly SCIG therapy was well tolerated in the study and that it results in high and stable serum IgG levels, offering an alternative therapy regimen to patients suffering from PAD.     

A case of natural killer/T cell lymphoma of the subcutis resembling subcutaneous panniculitis-like T cell lymphoma

A case of nasal type natural killer (NK)/T cell lymphoma of the subcutis showing clinical and morphological features that resemble subcutaneous panniculitis-like T cell lymphoma (SPTCL) is presented. A 73-year-old man presented with swelling of the left arm and was diagnosed with panniculitis by a dermatologist. It was concluded from a skin biopsy specimen that the patient had non-Hodgkin's lymphoma of the large cell, NK/T cell type because the neoplastic cells showed polyclonal CD3 immunoreactivity. Treatment with interferon-gamma was initiated, but the patient died of disseminated intravascular coagulation and multiple organ failure 2 months after the initial symptoms appeared. However, involvement of additional organs by the lymphoma was not apparent clinically. An autopsy was not performed. A routinely stained section of the biopsy skin specimen revealed massive necrosis of the subcutaneous fat, karyorrhexis admixed with reactive histiocytes, and large atypical lymphoid cells. Immunoreactivity for polyclonal CD3 was present in the perinuclear region, but absent in the neoplastic cell membranes. CD56, CD45RO (UCHL-1), CD43 (MT1), CD45 (leukocyte common antigen), and the cytotoxic molecules perforin, granzyme B and TIA-1 were positive, but CD20 (L26), CD4, CD8, and betaF1 were negative. Epstein-Barr virus (EBV) mRNA was detected in the nuclei of neoplastic cells by in situ hybridization. Subcutaneous panniculitis-like T cell lymphoma is reported to be an EBV-negative, clonal T cell neoplasm. Although this case showed clinical and morphological features that resembled SPTCL, perinuclear polyclonal CD3 staining and membranous CD56 reactivity seen in neoplastic cells were suggestive of NK cells. Furthermore, the neoplastic cells were positive for EBV. This case is considered to be a NK/T cell lymphoma of the subcutis resembling SPTCL. It is believed that it is important to recognize such a tumor because patients may undergo a fulminant clinical course, despite the tumor being localized in the subcutaneous adipose tissue.     

Golimumab in the treatment of psoriatic arthritis

ABSTRACT

Introduction: Psoriatic arthritis (PsA) is an inflammatory arthritis that can be aggressive and destructive, resulting in significant morbidity. While many new agents have been approved for the treatment of PsA over the past decade, TNF inhibitors (TNFi)remain an anchor treatment, in part based on extensive clinical experience. Recently, the TNFi golimumab was approved for intravenous use in PsA.

Areas covered: This expert review presents an overview of the currently available treatment options for PsA with a focus on the evidence from clinical trials supporting the use of golimumab in PsA. This information is placed in context with recent advances in the understanding of PsA pathogenesis and treatment.

Expert commentary: The rapid growth of treatment options available for PsA has brought the prospect of personalized treatment selection closer to reality but improved understanding of the domains of PsA and new biomarkers may be needed before such changes reach the clinic. Until patients who are most likely to benefit from a given agent can be identified and then treated accordingly, TNFi will likely remain a central option and their further development, such as the introduction of an intravenous form of golimumab, remains an important part of treatment improvement.