Glycated hemoglobin A: A predictor of outcome in trauma admissions to intensive care unit

Background and Aim:

Although large studies have demonstrated the association between hyperglycemia and adverse intensive care unit (ICU) outcomes, it is yet unclear which subset of patients benefit from tight sugar control in ICU. Recent evidence suggests that stress induced hyperglycemia (SIH) and co-incidentally detected diabetes mellitus are different phenomena with different prognoses. Differentiating SIH from diabetic hyperglycemia is challenging in ICU settings. We followed a cohort of trauma patients admitted to a surgical intensive care unit (SICU) to evaluate if initial glycated hemoglobin A (HbA₁c) level predicts the outcome of admission.

Materials and Methods:

A cohort of 120 consecutive admissions to SICU following trauma were recruited and admission blood sugar and HbA₁c were measured. Outcomes were prospectively measured by blinded ICU doctors. A logistic regression model was developed to assess if HbA₁c predicts poor outcomes in these settings.

Results:

Nearly 24% of the participants had HbA₁c ≥ 6. Those with HbA₁c ≥ 6 had 3.14 times greater risk of poor outcome at the end of hospital stay when compared to those with HbA₁c < 6 and this risk increased to an odds ratio of 4.57 on adjusting for other significant predictors: Acute Physiology and Chronic Health Evaluation II, injury severity score, admission blood sugar and age at admission.

Conclusions:

Substantial proportion of trauma admissions has underlying diabetes. HbA₁c, a measure of pre admission glycaemic status is an important predictor of ICU outcome in trauma patients.     

Modeling of cancer metastasis and drug resistance via biomimetic nano-cilia and microfluidics

Three-dimensional (3D) tissue culture platforms that are capable of mimicking in vivo microenvironments to replicate physiological conditions are vital tools in a wide range of cellular and clinical studies. Here, learning from the nature of cilia in lungs – clearing mucus and pathogens from the airway – we develop a 3D culture approach via flexible and kinetic copolymer-based chains (nano-cilia) for diminishing cell-to-substrate adhesion. Multicellular spheroids or colonies were tested for 3–7 days in a microenvironment consisting of generated cells with properties of putative cancer stem cells (CSCs). The dynamic and reversible regulation of epithelial–mesenchymal transition (EMT) was examined in spheroids passaged and cultured in copolymer-coated dishes. The expression of CSC markers, including CD44, CD133, and ABCG2, and hypoxia signature, HIF-1α, was significantly upregulated compared to that without the nano-cilia. In addition, these spheroids exhibited chemotherapeutic resistance in vitro and acquired enhanced metastatic propensity, as verified from microfluidic chemotaxis assay designed to replicate in vivo-like metastasis. The biomimetic nano-cilia approach and microfluidic device may offer new opportunities to establish a rapid and cost-effective platform for the study of anti-cancer therapeutics and CSCs.     

Allergic rhinitis and its impact on asthma: an evidence-based treatment strategy for allergic rhinitis

The overall pathogenic view of respiratory allergy has deeply changed and evolved during the last ten years. Much emphasis has been laid to the relationship between rhinitis and asthma, which is between the upper and the lower respiratory airways. This strict link has been evidenced through clinical observations and epidemiological studies and also on the basis of immunological observations and outcomes of therapy. Furthermore, the frequent co-existence of rhinitis and asthma (up to 80 percent of asthmatic patients have co-existing allergic rhinitis, while up to 40 percent of allergic rhinitis patients have asthma, the coexistence of sinusitis and asthma, the presence of rhinitis as a risk factor for developing asthma, further emphasize this link and together lead to the operative definition of Allergic Rhinobronchitis or, United Airways Disease (UAD). The strict link existing between upper and lower respiratory tract can be also regarded from the viewpoint of therapeutical outcomes. The more detailed knowledge of the intricate mechanisms sustaining allergic inflammation in the respiratory tract (i.e. antigen presentation, cytokines, chemokines and adhesion molecules) has clarified the functional relationships between nose and lung. Thus allergic rhinitis or asthma is not a disease confined to a specific target organ, but rather a disorder of the whole respiratory tract, with a range of clinical manifestations, leading to relevant diagnostic and therapeutic implications as indicated in the WHO Initiative ARIA, the first evidence-based guideline emphasizing the impact of allergic rhinitis on asthma and where a step-wise treatment strategy targeting both the upper and lower airway effectively has been proposed. Moreover, the use of novel potential therapies that target both rhinitis and asthma like antileukotrienes or anti-IgE are indeed a future strategy.     

A novel frame shift mutation in the HMG box of the SRY gene in a patient with complete 46,XY pure gonadal dysgenesis.

Pure gonadal dysgenesis or Swyer syndrome is a sex-reversal disorder resulting from embryonic testicular regression sequences especially during the first few weeks of fetal life and is induced by mutations in the SRY gene. In the present report, we describe a nonmosaic XY sex-reversed female with pure gonadal dysgenesis. Molecular analysis using sequential PCR to detect Y chromosomal microdeletions showed the presence of SRY, ZFY and AZFa, b and c regions. Automated sequencing of the SRY region revealed a new mutation (deletion of A (adenine) in codon 82 at position +244), leading to a frame shift mutation within the helix I of the HMG-box domain. This mutation generates a truncated protein and is very likely to produce an impairment of SRY DNA binding activity. The present findings further support the functional importance of the putative DNA binding activity of the SRY HMG-box domain.     

Bronchioloalveolar lavage in the diagnosis of CMV pneumonitis in lung transplant recipients: An immunocytochemical study

Cytomegalovirus (CMV) pneumonitis is a common opportunistic infection in lung transplant recipients. Its diagnosis usually rests on the identification of viral inclusions in lung parenchyma obtained by transbronchial biopsy, or by examination of the cytologic material obtained by bronchioloalveolar lavage (BAL). To determine whether the use of immunocytochemistry (ICC) increases the sensitivity of cytology in the diagnosis of CMV pneumonitis, we retrospectively selected 17 cases in which transbronchial biopsy and BAL were performed simultaneously, and had positive histology with negative cytology. Five negative controls were selected. The 22 slides were decolorized and restained with ICC for CMV. Of the 17 slides, nine (53%) showed cells with positive nuclear staining. All controls were negative. These results were then correlated with the number of infected cells present in the biopsy tissue, and the location of the cells (interstitial vs. intraalveolar). A good correlation was found between positive cytology and intraalveolar location of infected cells, and no correlation was seen between number of infected cells in the biopsy and the positive cytology. In summary, although histologic evaluation of lung parenchyma obtained by transbronchial biopsy is more sensitive for diagnosis of CMV pneumonitis, the sensitivity of the cytologic evaluation of BAL material can be increased by the use of ICC. The likelihood of positive ICC seems to be related to the presence of infected cells in the alveolar space rather than to the number of infected cells. Diagn. Cytopathol. 16:350–352, 1997. © 1997 Wiley-Liss, Inc.     

Performance of a commercial, type-specific enzyme-linked immunosorbent assay for detection of herpes simplex virus type 2-specific antibodies in Ugandans

Two hundred forty-eight human immunodeficiency virus (HIV)-positive and 496 HIV-negative subjects in Uganda were tested by HerpeSelect herpes simplex virus type 2 enzyme-linked immunosorbent assay (ELISA) and Western blotting to optimize the ELISA for use in this population. A higher index cutoff value was required for optimal sensitivity and specificity, and overall performance of the assay was not affected by HIV status.     

Spike patterning by Ca2+-dependent regulation of a muscarinic cation current in entorhinal cortex layer II neurons

In entorhinal cortex layer II neurons, muscarinic receptor activation promotes depolarization via activation of a nonspecific cation current (I(NCM)). Under muscarinic influence, these neurons also develop changes in excitability that result in activity-dependent induction of delayed firing and bursting activity. To identify the membrane processes underlying these phenomena, we examined whether I(NCM) may undergo activity-dependent regulation. Our voltage-clamp experiments revealed that appropriate depolarizing protocols increased the basal level of inward current activated during muscarinic stimulation and suggested that this effect was due to I(NCM) upregulation. In the presence of low buffering for intracellular Ca(2+), this upregulation was transient, and its decay could be followed by a phase of I(NCM) downregulation. Both up- and downregulation were elicited by depolarizing stimuli able to activate voltage-gated Ca(2+) channels (VGCC); both were sensitive to increasing concentrations of intracellular Ca(2+)-chelating agents with downregulation being abolished at lower Ca(2+)-buffering capacities; both were reduced or suppressed by VGCC block or in the absence of extracellular Ca(2+). These data indicate that relatively small increases in [Ca(2+)](i) driven by firing activity can induce upregulation of a basal muscarinic depolarizing-current level, whereas more pronounced [Ca(2+)](i) elevations can result in I(NCM) downregulation. We propose that the interaction of activity-dependent positive and negative feedback mechanisms on I(NCM) allows entorhinal cortex layer II neurons to exhibit emergent properties, such as delayed firing and enhanced or suppressed responses to repeated stimuli, that may be of importance in the memory functions of the temporal lobe and in the pathophysiology of epilepsy.     

Sleep deprivation effects on growth factor expression in neonatal rats: a potential role for BDNF in the mediation of delta power

The sleeping brain differs from the waking brain in its electrophysiological and molecular properties, including the expression of growth factors and immediate early genes (IEG). Sleep architecture and homeostatic regulation of sleep in neonates is distinct from that of adults. Hence, the present study addressed the question whether the unique homeostatic response to sleep deprivation in neonates is reflected in mRNA expression of the IEG cFos, brain-derived nerve growth factor (BDNF), and basic fibroblast growth factor (FGF2) in the cortex. As sleep deprivation is stressful to developing rats, we also investigated whether the increased levels of corticosterone would affect the expression of growth factors in the hippocampus, known to be sensitive to glucocorticoid levels. At postnatal days 16, 20, and 24, rats were subjected to sleep deprivation, maternal separation without sleep deprivation, sleep deprivation with 2 h recovery sleep, or no intervention. mRNA expression was quantified in the cortex and hippocampus. cFos was increased after sleep deprivation and was similar to control level after 2 h recovery sleep irrespective of age or brain region. BDNF was increased by sleep deprivation in the cortex at P20 and P24 and only at P24 in the hippocampus. FGF2 increased during recovery sleep at all ages in both brain regions. We conclude that cortical BDNF expression reflects the onset of adult sleep-homeostatic response, whereas the profile of expression of both growth factors suggests a trophic effect of mild sleep deprivation.