Causality Between the Amplitude and Frequency of Cardiac Oscillations

Using an information-theoretic approach, causality between the systolic amplitude in blood pressure and the frequency of the heart beat was analyzed. Blood pressure and ECG were noninvasively recorded in young, healthy subjects. Three successive measurements were performed: during spontaneous breathing and during paced respiration—at frequencies both higher and lower than that of spontaneous respiration. We demonstrate that the amplitude and frequency of the cardiac rhythm are synchronized for most of the time. The synchronization is stronger during paced respiration at a frequency lower than that of spontaneous breathing. Episodes where the cardiac frequency was driven by the systolic pressure were also detected during slow, paced respiration.     

Stress-Related Changes in β-Endorphin Processing: The Limitations of Slaughterhouse Material

In the sheep, unlike many other species, a significant proportion (>25%) of immunoreactive β-endorphin in the anterior pituitary is post-translationally modified to opioid-inactive, α-N-acetylated forms. In a study to determine the precise molecular nature of α-N-acetylated β-endorphin immunoreactivity, we noted a striking difference in high-performance liquid chromatography profiles of anterior pituitary extracts between sheep killed on the farm, and age-, sex- and strain-matched slaughterhouse animals. These altered patterns of a-N-acetylated β-endorphin processing were reproduced in farm animals by chronic (≤ 4 days) treatment with the synthetic glucocorticoid dexamethasone; in contrast dexamethasone had no effect on a-N-acetylated β-endorphin processing in hypothalamo-pituitary disconnected sheep. These data suggest that (1) the change in processing is a stress response, mediated by prolonged glucocorticoid exposure, (2) this effect is central, rather than a direct effect on the pituitary, and (3) the relative abundance of various peptide sequences in slaughterhouse-derived material may not reflect their abundance under more physiological conditions.     

Modulation of human polymorphonuclear neutrophil functions by α1acid glycoprotein

₁-Acid glycoprotein (₁-AGP), a naturally occurring human plasma protein and acute-phase reactant, was extracted by a two-step procedure from sera collected from four healthy men. Its activity was testedin vitro on human polymorphonuclear (PMN) functions (migration, aggregation, O ₂ ^– generation). ₁,-AGP was not chemoattractant but inhibited the PMN response to the chemoattractant formylmethionyl-leucyl-phenylalanine without affecting spontaneous migration (Boyden and agarose methods of assessment). At concentrations between 0.15 and 0.45 mg/ml, ₁AGP exerted an aggregating effect with a maximal effective concentration of 0.3 mg/ml. ₁-AGP inhibited superoxide generation by PMNs stimulated either by opsonized zymosan or phorbol myristate acetate. This inhibition varied according to the intensity of the stimulation. At low stimulus concentrations, a dose-dependent inhibition of membrane-associated PMN responsiveness to soluble or particulate stimuli was observed. These findings suggest that ₁-AGP may be able to prevent PMN activation in the course of inflammatory processesin vivo.     

Estrogen receptor negative and progesterone receptor positive primary breast cancer: Pathological characteristics and clinical outcome

The expression of estrogen (ER) and progesterone (PgR) receptors was analyzed in a retrospective series of 3000 patients who had operable primary breast cancer. Patients were stratified according to ER and PgR status and the study was focused on the two groups (ER–PgR+ and ER–PgR–) of patients whose tumors contained low levels of ER (< 15 fmol/mg protein), regarding potential response to endocrine therapy. The comparison of clinical or histological characteristics between ER–PgR+ and ER–PgR– patients was analyzed as well as the disease-related death and survival. The mean follow-up was 86.3 months. Among the 529 ER–patients, 62 were PgR+ (12%), whereas 467 were PgR– (88%). The ER–PgR+ and ER–PgR– populations represented 2% and 15.6% of the overall population, respectively. In ER– tumors, the PgR status was significantly related to: age, menopausal status, tumor size, SBR grade, and histological type, but not to the type of surgical treatment or to lymph node involvement. ER–PgR+ tumors had smaller size (64% T1 vs 43%) (p=0.004) and were more frequently grade I (28% vs 12%) than ER–PgR– ones (p < 0.001). In addition, the patients with ER–PgR+ tumors were significantly younger (49.4 years vs 58.4 years; p < 0.0001), and were more frequently premenopausal (76% vs 36%; p < 0.001). The disease-free interval and the metastasis-free survival tended to be worse for ER–PgR– than for ER–PgR+ patients, but the difference was not statistically significant at 10 years. However, a small but significant difference in overall survival, in favor of the PgR+ group, was observed between the two groups during the first 5 years (p=0.03).We conclude that in combination with ER, PgR status defines a group of patients with clinical and biological specificity, which could be considered for specific endocrine therapy.     

Potential therapeutic effect of Allium cepa L. and quercetin in a murine model of Blomia tropicalis induced asthma

Background

Asthma is an inflammatory condition characterized by airway hyperresponsiveness and chronic inflammation. The resolution of inflammation is an essential process to treat this condition. In this study we investigated the effect of Allium cepa L. extract (AcE) and quercetin (Qt) on cytokine and on smooth muscle contraction in vitro and its therapeutic potential in a murine model of asthma.

Methods

AcE was obtained by maceration of Allium cepa L. and it was standardized in terms of quercetin concentration using high performance liquid chromatography (HPLC). In vitro, using AcE 10, 100 or 1000 μg/ml or Qt 3.5, 7.5, 15 μg/ml, we measured the concentration of cytokines in spleen cell culture supernatants, and the ability to relax tracheal smooth muscle from A/J mice. In vivo, Blomia tropicalis (BT)-sensitized A/J mice were treated with AcE 100, 1000 mg/kg or 30 mg/kg Qt. We measured cell influx in bronchoalveolar lavage (BAL), eosinophil peroxidase (EPO) in lungs, serum levels of Bt-specific IgE, cytokines levels in BAL, and lung histology.

Results

We observed a reduction in the production of inflammatory cytokines, a relaxation of tracheal rings, and a reduction in total number of cells in BAL and EPO in lungs by treatment with AcE or Qt.

Conclusion

AcE and Qt have potential as antiasthmatic drugs, as they possess both immunomodulatory and bronchodilatory properties.     

Pressure control inverse ratio ventilation as a method to reduce peak inspiratory pressure and provide adequate ventilation and oxygenation

Nineteen patients with ARDS or pneumonia who were ventilated with PcIRV on the Siemens-Elema Servo 900 C were retrospectively reviewed. The PcIRV reduced peak airway pressure, PEEP, increased Paw, and improved ventilation and oxygenation in these patients. When these patients were compared with themselves on prior conventional IPPV, all had a decrease in PIP, an increase in Paw and most had a decrease in VE, with no change in PaCO2 and an increase in PaO2. The increase in Paw may have contributed to this improved arterial oxygenation. High levels of PIP and PEEP during IPPV have been identified as risk factors in the development of barotrauma and residual parenchymal pulmonary damage. We propose that PcIRV allows for adequate ventilation and oxygenation with decreases in PIP, extrinsically added PEEP and inspired O2 concentration. This mode of ventilation may decrease the morbidity associated with IPPV utilizing high PIP and PEEP.     

Cold urticaria – What we know and what we do not know

Cold urticaria (ColdU) is a common form of chronic inducible urticaria characterized by the development of wheals, angioedema or both in response to cold exposure. Recent research and guideline updates have advanced our understanding and management of ColdU. Today, its pathophysiology is thought to involve the cold-induced formation of autoallergens and IgE to these autoallergens, which provoke a release of proinflammatory mediators from skin mast cells. The classification of ColdU includes typical and atypical subtypes. We know that cold-induced wheals usually develop on rewarming and resolve within an hour and that anaphylaxis can occur. The diagnosis relies on the patient's history and cold stimulation testing. Additional diagnostic work-up, including a search for underlying infections, should only be done if indicated by the patient's history. The management of ColdU includes cold avoidance, the regular use of nonsedating antihistamines and the off-label use of omalizumab. However, many questions regarding ColdU remain unanswered. Here, we review what is known about ColdU, and we present important unanswered questions on the epidemiology, underlying pathomechanisms, clinical heterogeneity and treatment outcomes. Our aim is to guide future efforts that will close these knowledge gaps and advance the management of ColdU.