Interaction between Placental Alkaline Phosphatase and ABO System Polymorphisms

Abstract. Placental alkaline phosphatase is a polymorphic glycoenzyme, produced by the fetal part of the placenta, which is found at an early stage of gestation and in considerable amount in the maternal bloodstream. Previous studies have shown an interaction of this polymorphism with that of ABO system during intrauterine life.
In the present study the relationship between placental alkaline phosphatase phenotype and feto-maternal isoimmunization in the ABO system was investigated. Isoimmunization was defined by a positive direct Coombs test on cord blood and/or jaundice in the neonatal period. In infants incompatible with their mothers in the B group, the incidence of the above-mentioned signs of isoimmunization was lower in the presence of allele PI^f1 of placental alkaline phosphatase. This relationship was not found in infants of group A.
The present observations suggest that placental alkaline phosphatase may play an important role in the maternal-fetal immunological relationships.     

Reappearance of alopecia areata in a coeliac patient during an unintentional challenge with gluten

A patient with coeliac disease presenting alopecia areas as the only symptom is described. Alopecia disappeared completely after a few months of strict gluten free diet and reappeared after an unintentional prolonged introduction of gluten. After a severe gluten free diet, a new and persistent hair growth in the alopecia areas was observed. The possibility a direct relationship in some cases, between coeliac disease and alopecia areata is confirmed.     

Allograft nephrectomy: what is the best surgical technique?

Background

The objective of this study was to evaluate differences in outcomes of allograft nephrectomies performed by extracapsular versus intracapsular techniques.

Methods

From 1993 to 2010, we performed 89 allograft nephrectomies, including 57 by extracapsular techniques and 32 by intracapsular, chosen according to feasibility at the beginning of the surgery. Fisher exact test and logistic regression were used for statistical analysis. Survival estimates after allograft nephrectomy were calculated according to the Kaplan-Meier method.

Results

After a mean graft survival of 49.7 months, the indications for transplant nephrectomy were chronic rejection (39.3%), acute rejection (22.5%), infection/sepsis (19.1%), gross hematuria (6.7%), renal vein thrombosis (6.7%), renal artery thrombosis (3.4%), and graft rupture (2.3%). Mean operative time, blood loss, transfusions, and complications were similar between the extracapsular and intracapsular groups. The only difference in surgical aspects between the 2 groups was the mean hospital stay, which was longer for the extracapsular group (13.8 vs 7.6 days; P = .01), a result that was confirmed by multivariate analysis (odds ratio, 1.05; 95% confidence interval, 1.0-1.1; P = .03).

Conclusions

Our experience showed no significant advantages in favor of the intracapsular technique except for a shorter length of hospital stay than after the extracapsular procedure.     

GlucoMen Day Continuous Glucose Monitoring System: A Screening for Enzymatic and Electrochemical Interferents

Background

While most of the common drugs with the potential to interfere with continuous glucose monitoring (CGM) systems are accessible over the counter and can be assumed by CGM patients without medical supervision, many other chemicals are frequently used to treat critically ill patients. Continuous glucose monitoring reading accuracy may also be compromised in patients characterized by abnormally high concentrations of physiological interferents. In this article, 22 species selected from endogenous and exogenous chemicals were screened as possible interferents of GlucoMen®Day (GMD), the new microdialysis-based CGM system from A. Menarini Diagnostics.

Method

Interference testing was performed according to the EP7-A2 guideline (Clinical and Laboratory Standards Institute 2005). Interference was evaluated at two levels of glucose, with each interferent additionally tested at two concentrations. Furthermore, two configurations of the GMD disposable sensor kit—one designed for subcutaneous application, the other for direct intravascular CGM—were challenged with interferent-spiked serum and blood samples, respectively.

Results

With the exception of dopamine (however, at very high, nonphysiological concentrations), no interference was observed for all the tested substances. Interestingly, none of the common electrochemical interferents (including ascorbic acid, acetaminophen, and salicylic acid, which represent the major specificity issue for the competing CGM systems) significantly affected the system’s output.

Conclusions

These results provide clear insights into the advantages offered by the use of a microdialysis-based CGM system that additionally relies on the detection of hydrogen peroxide at low operating potential. GlucoMen Day may become the CGM system of choice for those patients who require either regular administration of drugs or their glycemia to be tightly controlled in the intensive care unit or similar environments.     

Intradermal skin tests with Dermatophagoides pteronyssinus in asthmatic children: correlation with specific IgE and bronchial provocation tests.

The purpose of the present study was to compare the results of the skin tests, the specific IgE levels and bronchial provocation tests in a group of sensitive asthmatic children with a Dermatophagoides pteronyssinus extract standardized by the RAST inhibition method. Skin tests showed a positive 'end point' in twelve children of 0.5 U/ml antigen; in eleven 5 U/ml; seven of 50 U/ml; six of 500 U/ml. Specific IgE was present in thirty-three children (92%). A close relationship between positive skin tests and serum IgE levels was found. Bronchial provocation tests were positive in twenty-eight children (78%): eight children with both positive RAST and positive skin tests had negative bronchial provocation tests.     

Ocular adnexal lymphoma: clinical behavior of distinct World Health Organization classification subtypes

PURPOSE: To evaluate the clinical behavior and treatment outcome of ocular adnexal lymphomas classified by the World Health Organization system, with emphasis on marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT). MATERIALS AND METHODS: The clinicopathologic materials from 98 consecutive patients treated for ocular adnexal lymphoma were reviewed. Fourteen patients had prior lymphoma and 84 patients had primary disease (75% Stage I, 6% Stage III, and 19% Stage IV). Radiation (photons/electrons) was administered to 102 eyes to a median dose of 30.6 Gy. The mean follow-up was 82 months. RESULTS: The most common subtypes among the primary patients were MALT (57%) and follicular (18%) lymphoma. The 5-year actuarial local control rate in 102 irradiated eyes was 98%. Among the low-grade lymphomas, the 5-year local control rate correlated with the radiation dose in the MALT lymphoma subgroup (n = 53): 81% for <30 Gy and 100% for > or =30 Gy (p <0.01). For the non-MALT low-grade lymphomas such as follicular lymphoma (n = 30), the local control rate was 100% regardless of dose. For 39 Stage I MALT lymphoma patients treated with radiation alone, the distant relapse-free survival rate was 75% at 5 years and 45% at 10 years. Distant relapses were generally isolated and successfully salvaged by local therapy. The overall survival for this subgroup was 81% at 10 years, with no deaths from lymphoma. CONCLUSIONS: Dose-response data suggest that the optimal radiation dose for MALT lymphoma of the ocular adnexa is 30.6-32.4 Gy in 1.8-Gy fractions and follicular lymphoma is adequately controlled with doses in the mid-20 Gy range. The substantial risk of distant relapse in Stage I ocular adnexal MALT lymphoma underscores the importance of long-term follow-up for this disease and the need for additional comparative studies of MALT lymphoma of different anatomic sites.     

Therapeutic Targeting of Classical and Lectin Pathways of Complement Protects from Ischemia-Reperfusion-Induced Renal Damage

Ischemia-reperfusion injury is the major cause of delayed graft function in transplanted kidneys, an early event significantly affecting long-term graft function and survival. Several studies in rodents suggest that the alternative pathway of the complement system plays a pivotal role in renal ischemia-reperfusion injury. However, limited information is currently available from humans and larger animals. Here we demonstrated that 30 minutes of ischemia resulted in the induction of C4d/C1q, C4d/MLB, and MBL/MASP-2 deposits in a swine model of ischemia-reperfusion injury. The infusion of C1-inhibitor led to a significant reduction in peritubular capillary and glomerular C4d and C5b-9 deposition. Moreover, complement-inhibiting treatment significantly reduced the numbers of infiltrating CD163⁺, SWC3a⁺, CD4a⁺, and CD8a⁺ cells. C1-inhibitor administration led to significant inhibition of tubular damage and tubular epithelial cells apoptosis. Interestingly, we report that focal C4d-deposition colocalizes with C1q and MBL at the peritubular and glomerular capillary levels also in patients with delayed graft function. In conclusion, we demonstrated the activation and a pathogenic role of classical and lectin pathways of complement in a swine model of ischemia-reperfusion−induced renal damage. Therefore, inhibition of these two pathways might represent a novel therapeutic approach in the prevention of delayed graft function in kidney transplant recipients.Delayed graft function (DGF) is the primary early post-transplant complication of kidney recipients.¹ This event, histologically characterized by the presence of acute tubular necrosis, has been reported to occur in 25% to 30% of renal transplants.¹ DGF is commonly associated with a significantly longer hospital stay and an increase in peritransplant morbidity. Moreover, this early complication seems to result in a marked reduction in long-term graft survival.² Indeed, DGF is associated with an increased rate of acute rejection and a suboptimal renal function at 1-year post-transplantation.^1,2,3Ischemia followed by reperfusion plays a pivotal role in the pathogenesis of early graft damage.¹ Ischemia-reperfusion injury is characterized by two main features at the renal level: apoptosis of tubular cells and interstitial inflammation. Although many steps in the cascade of events leading to ischemia-reperfusion injury are unclear, the most promising potential mechanisms include recruitment and activation of inflammatory cells and local priming of the complement cascade.^4,5,6The complement system is a major constituent of the innate immune system, participating in the pathogenesis of tissue damage through sequential activation of different proteases. The priming of this proteolytic cascade may occur by classical, alternative, and lectin-mediated activation pathways, and generates several pro-inflammatory mediators.^6,7 Studies in animal models have shown complement activation in the kidney after ischemia-reperfusion, leading to the generation of several mediators of inflammation, such as C3a, C5a, and C5b-9.⁴ Mice deficient in complement components such as C6 show very limited damage after renal ischemia-reperfusion injury.⁸ Moreover, the use of anti-factor B or C5a-receptor antagonists has been shown to reduce renal damage due to ischemia-reperfusion.^9,10 Therefore, prevention of complement activation is currently considered one of the best therapeutic targets to prevent or limit ischemia-reperfusion−induced renal damage.^5,6,11 C1-inhibitor (C1INH) is a potent inhibitor of proteases of the classical and lectin complement pathways (C1r, C1s, and MASP2).^6,11,12 Animal studies show that C1INH can protect liver, intestine, heart, and brain tissue from ischemia-reperfusion damage.¹³ There are no published data on the effect of C1INH on ischemia-reperfusion−induced renal damage, since most of the existing evidence suggests that in this setting complement activation is mainly induced through the alternative pathway.^5,14 However, all data reported in the literature are from murine models, and no information is currently available from larger animals and/or human subjects.The aim of the present study was to investigate the pattern of complement activation in patients with DGF and to test the efficacy of a recombinant form of human C1INH (rhC1INH) in preventing renal damage in a swine model of warm ischemia-reperfusion injury.