Chemokine transport across human vascular endothelial cells.

Leukocyte migration across vascular endothelium is mediated by chemokines that are either synthesized by the endothelium or transferred across the endothelium from the tissue. The mechanism of transfer of two chemokines, CXCL10 (interferon gamma-inducible protein [IP]-10) and CCL2 (macrophage chemotactic protein [MCP]-1), was compared across dermal and lung microvessel endothelium and saphenous vein endothelium. The rate of transfer depended on both the type of endothelium and the chemokine. The permeability coefficient (Pe) for CCL2 movement across saphenous vein was twice the value for dermal endothelium and four times that for lung endothelium. In contrast, the Pe value for CXCL10 was lower for saphenous vein endothelium than the other endothelia. The differences in transfer rate between endothelia was not related to variation in paracellular permeability using a paracellular tracer, inulin, and immunoelectron microscopy showed that CXCL10 was transferred from the basal membrane in a vesicular compartment, before distribution to the apical membrane. Although all three endothelia expressed high levels of the receptor for CXCL10 (CXCR3), the transfer was not readily saturable and did not appear to be receptor dependent. After 30 min, the chemokine started to be reinternalized from the apical membrane in clathrin-coated vesicles. The data suggest a model for chemokine transcytosis, with a separate pathway for clearance of the apical surface.     

Donor origin Rh antibodies as a cause of significant hemolysis following ABO-identical orthotopic liver transplantation

A group A, D-positive patient underwent orthotopic liver transplantation from a group A, D-negative (cde/cde) donor. Anti-D and -E were eluted from the recipient's red cells and were found in the recipient's serum 13 days later, at which time significant hemolysis developed. These Rh antibodies appear to he secondary to passive transfer of sensitized donor lymphocytes, a rare finding following liver transplantation.     

Neuroendocrine mechanisms that delay and initiate puberty in higher primates

This paper highlights a series of studies using the male rhesus monkey that has led to a model for the control of the onset of puberty in higher primates. The model proposes that the timing of puberty in these species is governed by the duration of a central brake that, during juvenile development, holds in check the hypothalamic network of gonadotropin-releasing hormone (GnRH) neurons, which, in the adult, drive the pituitary-gonadal axis. The neurobiology of this hypothalamic brake, and the physiological mechanisms that time its application and removal, are incompletely understood. Nevertheless, the pubertal resurgence of pulsatile GnRH release, which terminates the juvenile phase of primate development and triggers the initiation of puberty in man and monkeys, is associated with structural and molecular remodeling of the hypothalamus. A major component of this developmental plasticity appears to involve neuropeptide Y (NPY). NPY inhibits GnRH release, and NPY gene expression in the hypothalamus is elevated during juvenile development when GnRH release is restrained. Since the changes in hypothalamic function and morphology that trigger primate puberty unfold in the absence of gonadal steroid feedback, the possibility is raised that, in addition to activating the pituitary-gonadal axis at this stage of development, they may also contribute directly to the causation of behaviors and affective states that emerge at adolescence.     

Mesenteric panniculitis does not confer an increased risk for cancers: A systematic review and meta-analysis

Background:Mesenteric panniculitis (MP) is a non-specific, localized inflammation at the mesentery of small intestines which often gets detected on computed tomography. An association with malignant neoplasms remains unclear. We performed a systematic review and meta-analysis to examine the association of malignancy with MP.Methods:MEDLINE, EMBASE, Web of Science, and Cochrane databases were searched for articles published from inception to 2020 that evaluated the association of malignant neoplasms with MP in comparison with control groups. Using random-effects method, a summary odds ratio (OR) estimate with 95% confidence intervals for malignant neoplasms in MP was estimated.Results:Four case-control studies reporting data on 415 MP patients against 1132 matched-controls met inclusion criteria and were analyzed. The pooled OR for finding a malignant neoplasm in patients with MP was 0.907 (95% CI: 0.688–1.196; P = .489). The heterogeneity was mild and non-significant. Also, there was no heightened risk of any specific type of malignancy with MP. Three more case-series with unmatched-control groups (MP: 282, unmatched-controls: 17,691) were included in a separate analysis where the pooled OR of finding a malignant neoplasm was 2.963 (95% CI: 1.434–6.121; P = .003). There was substantial heterogeneity in this group.Conclusion:This meta-analysis of matched controlled studies proves absence of any significant association of malignant neoplasms with MP. Our study also demonstrates that the putative association of malignancy with MP is mainly driven by uncontrolled studies or case-series.     

Predictability model of the need for extracorporeal membrane oxygenation in neonates with meconium aspiration syndrome treated with inhaled nitric oxide

Background

As the use of inhaled nitric oxide (iNO) resulted in a decline in the need for extracorporeal membrane oxygenation (ECMO) in neonates with hypoxic respiratory failure, iNO has become an accepted treatment modality even in non-ECMO centers. However, because not all neonates respond to iNO, the timely identification and transfer of nonresponders to an ECMO center are important.

Objectives

The objective of this study was to identify the risk factors predictive of the need of ECMO in neonates with hypoxic respiratory failure after the first 6 hours of iNO treatment in an ECMO center.

Methods and Patient Population

Forty-nine patients with hypoxic respiratory failure transferred for iNO therapy and potential ECMO during a 2-year period were identified in this retrospective study. None of the patients had received iNO before admission. Strict clinical guidelines were used to standardize lung inflation, cardiovascular support, and iNO administration and weaning and to define treatment failure. The relationship between treatment failure (ie, the need for ECMO) and a set of suspected risk factors after 6 hours of iNO administration was examined by logistic regression analysis.

Results

Twenty-two neonates responded to iNO (non-ECMO group) whereas 27 neonates failed and met ECMO criteria (ECMO group). There was no difference between the 2 groups in demographic data, ventilatory support, air leak syndrome at 6 hours of iNO treatment, and survival to discharge. However, the dose and duration of iNO therapy were predictive of the need for ECMO with an adjusted odds ratio of 1.12 (95% CI, 1.01-1.25; P = .04) and 0.45 (95% CI, 0.27-0.65; P = .0002), respectively.

Conclusions

By the end of the first 6 hours of iNO treatment and under the specific conditions established by the use of the clinical guidelines, the dose and the duration of iNO administration were predictive of the probability for the need of ECMO in this patient population. Thus, one can establish a center-specific predictability model for the need of ECMO in neonates with hypoxic respiratory failure treated with iNO if strict clinical guidelines for iNO administration and weaning and respiratory and cardiovascular support are used in the given center.     

Late right ventricular performance after mitral valve repair assessed by exercise echocardiography

Objectives

The aim of the study was to evaluate the right ventricular (RV) performance during exercise in patients who underwent mitral valve repair for chronic mitral valve insufficiency relative to healthy individuals and to assess exercise capacity using a semisupine ergometer.

Methods

We studied 56 patients who underwent mitral valve repair for degenerative posterior mitral leaflet prolapse between 2005 and 2014 and a control group of 13 healthy individuals. Clinical data were collected prospectively, and echocardiographic measurements of RV function were obtained at rest and at peak exercise.

Results

One-third of the study patients had RV systolic dysfunction as indicated by tricuspid annular plane excursion (TAPSE) at rest. Resting TAPSE was lower in the study group (16.7?±?3.3 mm) than in the control group (24.4?±?4.3 mm), p?<?0.001. TAPSE increased in both groups during exercise and exercise was shown to have a significant main effect on TAPSE F(1, 52)?=?80, p?<?0.001. TAPSE increased more in the control group and an interaction was detected between the participant groups (study group vs. control group) and exercise, F(1, 52)?=?24, p?<?0.001. In the study group, Poor postoperative RV function was associated with preoperative left ventricular dilatation but was not correlated with impaired maximum exercise capacity.

Conclusions

Despite the excellent clinical outcome during rest and exercise after mitral valve repair, our results suggest patients that have undergone mitral valve repair due to posterior leaflet prolapse have significantly reduced RV function at rest and during exercise compared to healthy controls at long-term follow-up, as measured by TAPSE.

     

Interferon-gamma expression in jejunal biopsies in experimental human cryptosporidiosis correlates with prior sensitization and control of oocyst excretion

To investigate the role of interferon (IFN)-gamma in human cryptosporidiosis, jejunal biopsies from experimentally infected volunteers and chronically infected AIDS patients were examined for IFN-gamma expression by in situ hybridization. IFN-gamma expression was compared with oocyst excretion, baseline serum anti-Cryptosporidium antibody, and symptoms. IFN-gamma mRNA was detected in biopsies from 13 of 26 volunteers after experimental infection but not in biopsies taken before C. parvum exposure or in biopsies from patients with AIDS-associated cryptosporidiosis. After challenge, 9 of 10 volunteers with baseline C. parvum antibody produced IFN-gamma, compared with 4 of 16 volunteers without baseline antibody (P<.01). Furthermore, IFN-gamma mRNA was detected in 9 of 13 volunteers who did not excrete oocysts, compared with 4 of 13 with organisms (P<.05). Thus, expression of IFN-gamma in the jejunum was associated with prior sensitization and absence of oocyst shedding. IFN-gamma production may explain the resistance to infection noted in sensitized persons but may not be involved in control of human primary infection.