Effects of resuscitation fluids on nonadaptive immune responses

BACKGROUND: Colloidal plasma-expander fluids are commonly used as an alternative to blood components in the resuscitation of patients suffering from hemorrhagic shock and trauma. Of these, hydroxyethyl starch is also used as a cryopreservative, and these dual properties have been utilized in the development of a blood storage system that allows the direct transfusion of red cells. The prolonged intravascular persistence of hydroxyethyl starch suggests that phagocytic clearance may be impaired and that the presence of hydroxyethyl starch could exacerbate transfusion-induced immunomodulation. STUDY DESIGN AND METHODS: The effects of colloidal resuscitation fluids on the activation response and phagocytic function of polymorphonuclear cells (PMNs) and monocytes in normal peripheral blood were examined. To mimic the hemolysis associated with cryopreservation, the effects of 1- and 5- percent red cell lysate were studied. Flow cytometric assays were used in all cases. RESULTS: The percentage of phagocytic monocytes and PMNs was not altered; nor were the rates of phagocytosis impaired after incubation with resuscitation fluids. Upregulation of cell surface integrin during activation was similarly unmodified by the fluids. CONCLUSION: Hydroxyethyl starch and other resuscitation fluids do not affect some important antimicrobial functions of the nonadaptive arm of the immune response. This suggests that posttrauma or transfusion- induced immunomodulation is not exacerbated by inhibition at this level.     

JunB as a potential mediator of PTHrP actions: new gene targets Ephrin B1 and VCAM‐1

Parathyroid hormone‐related protein (PTHrP) is an integral mediator of physiologic and pathologic processes and has demonstrated actions in the periodontium. PTHrP functions via AP‐1, and specifically through JunB. This study identified JunB‐dependent downstream mediators of PTHrP using OCCM cementoblastic transfectants with JunB over‐ or reduced expression. Over‐expressing cells showed an increase in proliferation, while the opposite was seen in siRNA transfected cells. Microarray analysis of over‐expressing cells revealed more than 1000 regulated genes. Three genes were investigated in more detail. The PTH/PTHrP receptor (PTHR1) and ephrin B1 (EfnB1) were down‐regulated, and vascular cell adhesion molecule‐1 (VCAM‐1) was up‐regulated with JunB over‐expression. JunB siRNA transfectants had increased PTHR1, but reduced ephrin B1 and unaltered VCAM‐1 in vitro. To validate these targets, parental OCCM cells and primary osteoblasts were treated with PTHrP, resulting in reduced PTHR1 and ephrin B1, and increased VCAM‐1. Cell transfectants were implanted subcutaneously in vivo, and microarray analysis and RT‐PCR performed. Over‐expression of JunB down‐regulated PTHR1 and ephrin B1, and increased VCAM‐1. JunB siRNA transfectant implants had increased PTHR1 and ephrin B1, but no altered VCAM‐1. These data highlight new gene targets for PTHrP and indicate JunB is a critical mediator of PTHrP actions.     

Viral kinetics in untreated versus treated acute HIV infection in prospective cohort studies in Thailand

Introduction : The extent of viral replication during acute HIV infection (AHI) influences HIV disease progression. However, information comparing viral load (VL) kinetics with and without antiretroviral therapy (ART) in AHI is limited. The knowledge gained could inform preventive strategies aimed at reducing VL during AHI and therapeutic strategies to alter the viral kinetics that may enhance the likelihood of achieving HIV remission. Methods : The analysis utilized VL data captured during the first year of HIV infection from two studies in Thailand: the RV217 study (untreated AHI, 30 participants and 412 visits) and the RV254 study (treated AHI, 235 participants and 2803 visits). Fiebig stages were I/II (HIV RNA+, HIV IgM−) and Fiebig III/IV (HIV IgM+, Western blot‐/indeterminate). Data were modelled utilizing spline effects within a linear mixed model, with a random intercept and slope to allow for between‐subject variability and adjustment for the differences in variability between studies. The number of knots in the quadratic spline basis functions was determined by comparing models with differing numbers of knots via the Akaike Information Criterion. Models were fit using PROC GLIMMIX in SAS v9.3. Results : At enrolment, there were 24 Fiebig I/II and 6 Fiebig III/IV individuals in the untreated group and 137 Fiebig I/II and 98 Fiebig III/IV individuals in the treated group. Overall, the median age was 27.5 years old, most were male (89%), and CRF01_AE was the most common HIV clade (76%). By day 12 (4 days after ART in RV254), the untreated group had a 2.7‐fold higher predicted mean VL level compared to those treated (predicted log VL 6.19 for RV217 and 5.76 for RV254, p = 0.05). These differences increased to 135‐fold by day 30 (predicted log VL 4.89 for RV217 and 2.76 for RV254) and 1148‐fold by day 120 (predicted log VL 4.68 for RV217 and 1.63 for RV254) (p < 0.0001 for both) until both curves were similarly flat at about day 150 (p = 0.17 between days 150 and 160). The VL trajectories were significantly different between Fiebig I/II and Fiebig III/IV participants when comparing the two groups and within the treated group (p < 0.001 for both). Conclusions : Initiating ART in AHI dramatically changed the trajectory of VL very early in the course of infection that could have implications for reducing transmission potential and enhancing responses to future HIV remission strategies. There is an urgency of initiating ART when acute infection is identified. New and inexpensive strategies to engage and test individuals at high risk for HIV as well as immediate treatment access will be needed to improve the treatment of acute infection globally. Clinical Trial Number : NCT00796146 and NCT00796263     

Anthropometry and secular changes in stature of urban Colombian women of differing socioeconomic status

Anthropometric dimensions were taken on 1,572 women, 18–44 years of age, from Cali, Colombia, from three different socioeconomic (SEC) groups: low (LEC), mid-low (MLEC), and upper (UEC). LEC and MLEC women were significantly shorter and had higher body mass indices (BMIs) than UEC women, and a significantly larger number had BMIs over 27.3 kg/m². There were no significant differences between SEC groups for skinfolds on the arm, but skinfolds on the trunk, the subscapular–triceps ratio, and the waist–hip ratio followed an inverse SEC gradient, indicating a greater tendency for upper body fat distribution in the lower SEC groups. SEC differences in body fatness and fat distribution diminished with age, suggesting that health risks associated with obesity and an upper body fat distribution may be similar in all three groups by ages 40–44 years. Secular changes in stature were similar, 0.12 cm/year for LEC/MLEC women and 0.15 cm/year for UEC women, and there was no indication that the statural differences between the groups is diminishing. The results indicate that women from Cali exhibit anthropometric characteristics seen in both developing countries (stature positively associated with SEC) and developed countries (fatness and centralized fat distribution inversely related to SEC). These findings may reflect the relative economic prosperity of Colombia as a “developing country”. © 1994 Wiley-Liss, Inc.     

Testicular neoplasms: 29 tumors studied by high-resolution US

High-resolution (10-MHz) ultrasonography produces extremely detailed anatomic images of the testis. The sonographic features most helpful in detecting tumors are mass, bright echogenic foci, and diffuse parenchymal texture change. Of 29 patients with testicular neoplasms, 21 (72%) had one or more masses, 19 (66%) had one or more echogenic foci, and nine (31%) had a diffuse parenchymal texture change. Bright echogenic foci were present in six (86%) of seven testes that had a regressed germ-cell tumor. In an attempt to define the histologic features of bright echogenic foci, we performed needle localization under real-time guidance on four operative specimens. We observed immature bone and cartilage, calcification, tubular atrophy and fibrosis, and focal noncalcific scarring. Discovery of occult testicular neoplasms was common (9/29); four patients were thought to have had "extragonadal" germ-cell tumors before abnormalities were found on the sonograms.