Prothrombin complex concentrate (Beriplex P/N) in severe bleeding: experience in a large tertiary hospital

Introduction

Major blood loss can often be life-threatening and is most commonly encountered in the settings of surgery and trauma. Patients receiving anticoagulant therapy are also at increased risk of bleeding. We investigated the use of a prothrombin complex concentrate (PCC; Beriplex P/N, CSL Behring, Marburg, Germany) to treat severe bleeding in a variety of settings: cardiac surgery, warfarin therapy and other surgery.

Methods

Thirty consecutive patients who had received PCC were identified from blood transfusion records. For cardiac surgery and warfarin reversal, PCC was administered in accordance with hospital protocols. PCC was administered to cardiac and other surgical patients responding poorly to recognized blood products, whereas it was administered first-line to patients with life-threatening bleeds and requiring warfarin reversal, in accordance with British Committee for Standards in Haematology guidelines. We conducted a retrospective analysis of patient records in order to ascertain PCC dose, use of other blood products and response to PCC (clotting screen results before and after PCC administration, haemostasis achievement, and survival).

Results

Six patients (20%) were excluded because of inadequate documentation (n = 5) or acquired haemophilia (n = 1). Therefore, 24 patients were included in the analysis: coronary artery bypass graft (n = 5), mitral/aortic valve replacement (n = 2), other surgery (n = 9) and warfarin reversal (n = 8). Most patients (83.3%) received no more than 1500 IU of Beriplex P/N 500. Considerable reduction in administration of other blood products was seen during the 24 hours after PCC administration. Partial or complete haemostasis was achieved in 14 out of 18 cases (77.8%). In total, 12 out of 24 patients (50%) died during the study; two-thirds of the deaths were considered unrelated to bleeding. No thrombotic complications or adverse drug reactions were observed.

Conclusion

This study emphasizes the value of PCC in reversing the effects of oral anticoagulant therapy in bleeding patients. It also demonstrates the potential value of PCC in controlling bleeding in patients undergoing cardiac and other surgical procedures. The use of PCC in bleeding patients without hereditary or anticoagulation-related coagulopathy is novel, and further investigation is warranted. In the future, it may be possible to use PCC as a substitute for fresh frozen plasma in this setting; adequate documentation is crucial for all blood products.     

Duration of sleep contributes to next-day pain report in the general population

Cross-sectional research in clinical samples, as well as experimental studies in healthy adults, suggests that the experiences of pain and sleep are bi-directionally connected. However, whether sleep and pain experiences are prospectively linked to one another on a day-to-day basis in the general population has not previously been reported. This study utilizes data from a naturalistic, micro-longitudinal, telephone study using a representative national sample of 971 adults. Participants underwent daily assessment of hours slept and the reported frequency of pain symptoms over the course of one week. Sleep duration on most nights (78.0%) was between 6 and 9h, and on average, daily pain was reported with mild frequency. Results suggested that hours of reported sleep on the previous night was a highly significant predictor of the current day's pain frequency (Z=-7.9, p<.0001, in the structural equation model); obtaining either less than 6 or more than 9h of sleep was associated with greater next-day pain. In addition, pain prospectively predicted sleep duration, though the magnitude of the association in this direction was somewhat less strong (Z=-3.1, p=.002, in the structural equation model). Collectively, these findings indicate that night-to-night changes in sleep affect pain report, illuminating the importance of considering sleep when assessing and treating pain.     

Adaptive visual memory reorganization in right medial temporal lobe epilepsy

Purpose: We investigated functional reorganization mechanisms of the human medial temporal lobe (MTL) for episodic memory, in patients suffering from medial temporal lobe epilepsy (MTLE) with hippocampal sclerosis (HS).
Methods: We used functional magnetic resonance imaging (fMRI) to measure brain activity changes during matched episodic encoding tasks of abstract words (Verbal) and line drawings (Visual), in patients with unilateral right MTLE undergoing presurgical evaluation and healthy controls.
Results: As expected, a significant interaction between material type and the side of MTL activity was present in the control group, with preferential involvement of the left hippocampus in verbal encoding and the right parahippocampal region in visual encoding. When compared with controls, right MTLE patients with intact performance activated a region in the left hippocampus more during visual encoding, which resulted in an interaction between group and hemisphere. Importantly, an effect of memory performance on visual encoding activity was observed in the patients, with greater engagement of the left MTL being associated with higher recognition scores. Interestingly, activity in the left MTL also depended on the epileptic seizure frequency, suggesting a role for this clinical parameter in the recruitment of contralateral regions.
Discussion: Taken together, these results indicate functional reorganization of the MTLs in right HS, through transfer of function from the right to the left hemisphere, and strongly suggest an adaptive role for such reorganization mechanism in supporting preserved visual memory.     

Effects of altered corticosteroid milieu on rat hippocampal neurochemistry and structure--an in vivo magnetic resonance spectroscopy and imaging study

Altered corticosteroid milieu induces changes in hippocampal volume, neuronal structure, neurochemistry and cognitive function in humans and rodents. This in vivo magnetic resonance spectroscopy (1H MRS) and imaging (MRI) study investigated whether long-term alterations of the corticosteroid milieu cause: (i) metabolic and/or (ii) structural changes of the rat hippocampus. Therefore, hypocortisolism was induced by adrenalectomy (ADX), normocortisolism by ADX with low-dose corticosterone replacement, and hypercortisolism by ADX and high-dose dexamethasone treatment (for 11 weeks, respectively). All groups including a control group (n=23) were studied by in vivo 1H MRS and MR volumetry. Effects of treatment on normalized hippocampal metabolites and volumes were tested for significance using one-factorial multivariate analysis of variance (MANOVA). Hypercortisolemic rats revealed significantly elevated glutamate. Hypocortisolemic rats showed significantly decreased myo-inositol ratio levels, and were associated with significantly reduced normalized hippocampal volumes. Our findings suggest chronic hypercortisolism to be associated with glutamate-mediated excitotoxicity in the absence of volumetric abnormalities. In contrast, hypocortisolism appears to be associated with neurodegenerative processes, altered astrocytic metabolism but preserved neuronal density.     

Functional gait analysis of trans-femoral amputees using two different single-axis prosthetic knees with hydraulic swing-phase control: Kinematic and kinetic comparison of two prosthetic knees

This paper reports a comparison of the gait patterns of trans-femoral amputees using a single-axis prosthetic knee that coordinates ankle and knee flexions (Proteor's Hydracadence system) with the gait patterns of patients using other knee joints without a knee-ankle link and the gait patterns of individuals with normal gait. The two patient groups were composed of 11 male trans-femoral amputees: six patients had the Hydracadence joint (Group 1) and five patients had other prosthetic knees (Group 2). The reference group was made up of 23 normal volunteers (Group 3). In this work, trunk, hip, knee, and ankle 3-D motion was assessed using the VICON system. Kinetic data were collected by two AMTI force plates, and the knee moment was calculated via the 3-D equilibrium equations. An original questionnaire was used to assess the participants' activity level and clinical background. The results reveal that, during stance, all knee types guaranteed security. After heel strike, the plantar flexion of the ankle enabled by the Hydracadence prosthesis seems to increase stability. During swing phase, hip and knee sagittal motion was nearly the same in both Group 1 and Group 2. By contrast, hallux and sole vertical positions were significantly higher in Group 1 than in Group 2; thus, it seems the link between the ankle joint and the knee joint makes foot clearance easier. No alteration of the lateral bending of the trunk was observed. The protocol proposed in this paper allows a functional comparison between prosthetic components by combining clinical data with objective 3-D kinematic and kinetic information. It might help to determine which prosthetic knees are best for a specific patient.     

The safety of pharmacological therapies for gastrointestinal conditions encountered during pregnancy

Properly assessing the safety of pharmacological therapies for gastrointestinal conditions encountered during pregnancy is a challenge on account of both the often limited controlled data available and the potentially confounding effect of the underlying disorders requiring treatment on fetal outcomes. Here, the available data with regard to gastrointestinal disorders specific to pregnancy, those that may be precipitated or exacerbated by pregnancy and those that may be pre-existing or arise concurrently during pregnancy are reviewed.     

Genetic variation of estrogen metabolism and the risks of cardiovascular disease

Genetic variation in estrogen-metabolizing genes and estrogen receptors influences estrogen metabolism and can potentially modify, at least in part, individual responses to hormone replacement therapy (HRT) or cardiovascular disease (CVD) susceptibility. Pharmacogenetics and association studies of estrogen metabolism genes and lipid levels, inflammatory markers, atherosclerosis and myocardial infarction are reviewed. The human estrogen receptor 1 gene is associated with estrogen metabolism and is the most frequently investigated gene. Few association studies between estrogen receptor 2 variants and CVD risk have been conducted. Although several phase I and II catabolism enzymes are responsible for critical steps in estrogen metabolism, genetic studies with these genes are scarce. Data presented here suggest that genetic variants might influence CVD risk and HRT response. However, no firm conclusions about the clinical implications of these markers can be made based on these studies.     

Acupuncture stimulation at Sanyinjiao: effect on the sodium pertechnetate bioavailability in rats

In clinical acupuncture, when acupuncture points are stimulated, several types of reflex responses can be evoked. Consequently, different categories of physiological responses are induced, which include changes in the activities of internal organs and tissues. The acupuncture point Sanyinjiao (SP6) has been used successfully to treat different human gastrointestinal conditions. The aim of this work was to investigate the effects of end-organ response induced by acupuncture point SP6 on the bioavailability of the radiopharmaceutical sodium pertechnetate (Na99mTcO4) in Wistar rats. Healthy rats were allocated into 2 groups, control-CG and treated-TG. TG was bilaterally stimulated at acupuncture point SP6 with stainless steel needles. Ocular plexus administration of Na99mTcO4 (3.7MBq) was carried out 10 min after every needle insertion in all animals. Ten minutes later, the animals were killed, the organs were isolated, the radioactivity was determined in a well gamma counter, and the percentage of injected dose per gram of tissue (%ID/g) was determined for each organ. The %ID/g was significantly altered (p < 0.05) in the small intestine of TG (0.56 +/- 0.09) when compared to CG (0.82 +/- 0.18). These results may suggest that this stimulation might induce physiological responses capable of altering the bioavailability of the radiopharmaceutical sodium pertechnetate. These findings aid in providing a better understanding of acupuncture and its effects on various organs and tissues.     

Isatins inhibit cyclooxygenase-2 and inducible nitric oxide synthase in a mouse macrophage cell line

Isatin is a versatile compound with a diversity of effects. We designed to investigate the inhibitory effect of isatin derivatives on lipopolysaccharide/interferon-gamma-induced expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) proteins, production of prostaglandin E(2) (PGE(2)), nitric oxide (NO), tumor necrosis factor (TNF-alpha), and their capacity to scavenge NO. Isatins inhibit TNF-alpha production and iNOS and COX-2 protein expression resulting on reduced levels of NO and PGE(2). Our results indicate isatin and it derivatives as inhibitors of iNOS and COX-2 enzymes, which might be used as anti-inflammatory and antitumoral agents.     

The Use of Neural Network Technology to Model Swimming Performance

The aims of the present study were: to identify the factors which are able to explain the performance in the 200 meters individual medley and 400 meters front crawl events in young swimmers, to model the performance in those events using non-linear mathematic methods through artificial neural networks (multi-layer perceptrons) and to assess the neural network models precision to predict the performance. A sample of 138 young swimmers (65 males and 73 females) of national level was submitted to a test battery comprising four different domains: kinanthropometric evaluation, dry land functional evaluation (strength and flexibility), swimming functional evaluation (hydrodynamics, hydrostatic and bioenergetics characteristics) and swimming technique evaluation. To establish a profile of the young swimmer non-linear combinations between preponderant variables for each gender and swim performance in the 200 meters medley and 400 meters font crawl events were developed. For this purpose a feed forward neural network was used (Multilayer Perceptron) with three neurons in a single hidden layer. The prognosis precision of the model (error lower than 0.8% between true and estimated performances) is supported by recent evidence. Therefore, we consider that the neural network tool can be a good approach in the resolution of complex problems such as performance modeling and the talent identification in swimming and, possibly, in a wide variety of sports.

Key points

• The non-linear analysis resulting from the use of feed forward neural network allowed us the development of four performance models.
• The mean difference between the true and estimated results performed by each one of the four neural network models constructed was low.
• The neural network tool can be a good approach in the resolution of the performance modeling as an alternative to the standard statistical models that presume well-defined distributions and independence among all inputs.
• The use of neural networks for sports sciences application allowed us to create very realistic models for swimming performance prediction based on previous selected criterions that were related with the dependent variable (performance).

Key words: Evaluation, age group swimmers, individual medley, front crawl.