Commentary on the safety of red cells preserved in extended-storage media for neonatal transfusions

Red cells preserved in extended-storage media are the standard product dispensed by many regional blood centers. When the red cells are intended for neonatal transfusion, concern exists about the safety of the relatively high quantities of additives present in these media. Definitive studies to address these concerns are not available. Therefore, to estimate the effects of additives and to delineate circumstances in which they might be harmful, the quantities transfused in defined clinical settings were calculated, and the following recommendations are offered for transfusing infants less than 4 months of age. First, red cells preserved in extended-storage media should present no substantive risks when used for small-volume (approximately 10 mL/kg) transfusions of premature infants and can be used without additional processing. Second, the risks of the most premature neonatal patients or those with severe renal and/or hepatic insufficiency cannot be defined clearly, and, because data are not available to ensure safety for these infants, removal of the additive medium and resuspension of the red cells in saline or albumin solution immediately before transfusion are recommended. Third, following a similar rationale, it seems prudent to avoid using entire units of red cells preserved in extended-storage media in massive transfusion settings (e.g., exchange transfusion, cardiac surgery, and extracorporeal membrane oxygenation). In these settings, the preservative medium should be removed and the red cells resuspended in the fluid that is most appropriate for the procedure that is planned. It must be emphasized that these recommendations are based on calculations and hypothetical settings, not actual data. Accordingly, they are tentative and should be altered as definitive information becomes available.     

Intraindividual Reproducibility of Heart Rate Variability

Heart rate variability was determined from three consecutive Holter recordings performed on days 1, 7, and 28 in 17 normal subjects, in 13 patients with angiographically normal coronary arteries, and in 9 patients with remote myocardial infarctions. Group data of several time and frequency domain measures of heart rate variability were highly reproducible (correlation coefficients 0.629–0.894). However, some individuals exhibited considerably larger day-to-day variations in heart rate variability. Single heart rate indices differed by up to 50% between two Holter recordings. Such potential differences must be considered when repeated heart rate variability determinations are used to assess changes in neurocardiac reflex regulation or effects of therapeutic interventions.     

Mycobacterial Infections After Renal Transplantation

Mycobacterial infections occurred in 11 of 633 (1.7 per cent)recipients of successful renal transplants. There were no casesof tuberculosis in patients receiving chemoprophylaxis, butamongst those who did not receive prophylaxis disease occurredin six of the 27 (22 per cent) high-risk patients. The majorcause of morbidity during treatment was renal allograft rejection,largely due to reduction in immunosuppressive drug therapy.     

Mid-term results of a metal-backed glenoid component in total shoulder replacement

Total shoulder replacement is a successful procedure for degenerative or some inflammatory diseases of the shoulder. However, fixation of the glenoid seems to be the main weakness with a high rate of loosening. The results using all-polyethylene components have been better than those using metal-backed components. We describe our experience with 35 consecutive total shoulder replacements using a new metal-backed glenoid component with a mean follow-up of 75.4 months (48 to 154). Our implant differs from others because of its mechanism of fixation. It has a convex metal-backed bone interface and the main stabilising factor is a large hollow central peg. The patients were evaluated with standard radiographs and with the Constant Score, the Simple Shoulder Test and a visual analogue scale. All the scores improved and there was no loosening, no polyethylene-glenoid disassembly and no other implant-related complications. We conclude that a metal-backed glenoid component is a good option in total shoulder replacement with no worse results than of those using a cemented all-polyethylene prosthesis.     

Modified MacLaughlin procedure in the treatment of neglected posterior dislocation of the shoulder

Posterior dislocation of the shoulder is an unusual injury that most often occurs secondary to a highenergy trauma. Unfortunately the diagnosis is commonly missed, thus making its treatment a challenge. Neglected posterior dislocation is mainly characterised by an impression fracture on the anterior articular surface of the humeral head, which makes the dislocation often difficult to reduce. Diagnosis is based upon a careful history assessment, physical examination and radiological findings. Several treatment approaches have been described. The modified MacLaughlin procedure in our hands has been shown to be a reproducible technique allowing good results at medium- and long-term follow-up. According to our experience it is possible to adopt this technique also in patients with a locked posterior dislocation older than 6 months or in cases with a humeral head defect up to 50% when a shoulder prosthesis is not a good indication. Poorer results should be expected in patients with an associated fracture of the proximal humerus.     

Atypical cutaneous manifestation of HSV-2 with Candida albicans co-infection in a patient with HIV-1

Herpes simplex virus type 2 (HSV-2) infection was one of the first opportunistic infections identified among patients with AIDS. In the literature there are many data suggesting that the natural history of HSV-2 infection is altered in HIV-HSV-2 co-infected patients. Furthermore, a relationship between HIV seropositivity and HBV infection because of their analogous way of transmission is also described. We report the case of a 37-year-old patient who suffered from multiple painful ulcerative lesions of the perianal region. Laboratory examination showed positivity for HIV and HBV infections. In HIV-positive patients perianal HSV-2 can have atypical manifestations, especially if co-infection by Candida albicans occurs.     

Protection against inflammation- and autoantibody-caused fetal loss by the chemokine decoy receptor D6

Fetal loss in animals and humans is frequently associated with inflammatory conditions. D6 is a promiscuous chemokine receptor with decoy function, expressed in lymphatic endothelium, that recognizes and targets to degradation most inflammatory CC chemokines. Here, we report that D6 is expressed in placenta on invading extravillous trophoblasts and on the apical side of syncytiotrophoblast cells, at the very interface between maternal blood and fetus. Exposure of D6-/- pregnant mice to LPS or antiphospholipid autoantibodies results in higher levels of inflammatory CC chemokines and increased leukocyte infiltrate in placenta, causing an increased rate of fetal loss, which is prevented by blocking inflammatory chemokines. Thus, the promiscuous decoy receptor for inflammatory CC chemokines D6 plays a nonredundant role in the protection against fetal loss caused by systemic inflammation and antiphospholipid antibodies.     

Genetic contributors to frontotemporal lobar degeneration: beyond monogenic disease

Frontotemporal Lobar Degeneration (FTLD) is a genetically and pathologically heterogeneous disorder characterized by behavioral change, executive dysfunction and language impairment associated with frontal and temporal lobe degeneration. Three major clinical subtypes have been identified so far, namely behaviour variant Frontotemporal dementia (bvFTD), Semantic Dementia (SD) and Progressive Non-Fluent Aphasia (PNFA). FTLD might also overlap with atypical parkinsonisms or motor neuron disease. Several pathogenetic mutations have been associated with specific pathological and clinical correlates. FTLD associated with either Microtuble Associated Protein Tau (MAPT) or Progranulin (PGRN) mutations is recognised as the most common form of autosomal dominant inherited disorder. However, monogenic mutations account for only about one third of all FTLD cases. Several studies have evaluated the contribution of genetic background in non-monogenic forms of FTLD, with the attempt to establish its role in increasing disease risk and in modulating clinical phenotypes. Specific MAPT and PGRN polymorphisms have been demonstrated to affect disease onset, clinical features and prognosis of FTLD, and genetic variations within other genes appear to play a role in influencing disease risk and clinical expression of FTLD. The aim of the present review is to discuss the impact and the role of genetic background in non-monogenic forms of FTLD, to highlight new potential pathogenetic and therapeutic targets.     

Biochemical and behavioural characterization of EMPA,a novel high-affinity,selective antagonist for the OX2 receptor

Background and purpose:

The OX₂ receptor is a G-protein-coupled receptor that is abundantly found in the tuberomammillary nucleus, an important site for the regulation of the sleep-wake state. Herein, we describe the in vitro and in vivo properties of a selective OX₂ receptor antagonist, N-ethyl-2-[(6-methoxy-pyridin-3-yl)-(toluene-2-sulphonyl)-amino]-N-pyridin-3-ylmethyl-acetamide (EMPA).

Experimental approach:

The affinity of [³H]EMPA was assessed in membranes from HEK293-hOX₂-cells using saturation and binding kinetics. The antagonist properties of EMPA were determined by Schild analysis using the orexin-A-or orexin-B-induced accumulation of [³H]inositol phosphates (IP). Quantitative autoradiography was used to determine the distribution and abundance of OX₂ receptors in rat brain. The in vivo activity of EMPA was assessed by reversal of [Ala¹¹,D-Leu¹⁵]orexin-B-induced hyperlocomotion during the resting phase in mice and the reduction of spontaneous locomotor activity (LMA) during the active phase in rats.

Key results:

[³H]EMPA bound to human and rat OX₂-HEK293 membranes with K_D values of 1.1 and 1.4 nmol·L⁻¹ respectively. EMPA competitively antagonized orexin-A-and orexin-B-evoked accumulation of [³H]IP at hOX₂ receptors with pA₂ values of 8.6 and 8.8 respectively. Autoradiography of rat brain confirmed the selectivity of [³H]EMPA for OX₂ receptors. EMPA significantly reversed [Ala¹¹,D-Leu¹⁵]orexin-B-induced hyperlocomotion dose-dependently during the resting phase in mice. EMPA, injected i.p. in rats during the active phase, reduced LMA dose-dependently. EMPA did not impair performance of rats in the rotarod procedure.

Conclusions and implications:

EMPA is a high-affinity, reversible and selective OX₂ receptor antagonist, active in vivo, which should prove useful for analysis of OX₂ receptor function.