Stability of coagulation assays performed in plasma from citrated whole blood transported at ambient temperature

Many preanalytical variables affect the results of coagulation assays. A possible way to control some of them would be to accept blood specimens shipped in the original collection tube. The aim of our study was to investigate the stability of coagulation assays in citrated whole blood transported at ambient temperature for up to two days after specimen collection. Blood samples from 59 patients who attended our haematology outpatient ward for thrombophilia screening were transported at ambient temperature (outdoor during the day, indoor overnight) for following periods of time: <1 hour, 4-6, 8-12, 24-28 and 48-52 hours prior to centrifugation and plasma-freezing. The following coagulation tests were performed: PT, aPTT, fibrinogen, FII:C, FV:C, FVII:C, FVIII:C, FIX:C, FX:C, FXI:C, VWF:RCo, VWF:Ag, AT, PC activity, total and free PS antigen, modified APC-sensitivity-ratio, thrombin-antithrombin-complex and D-dimer. Clinically significant changes, defined as a percentage change of more than 10% from the initial value, were observed for FV:C, FVIII:C and total PS antigen starting at 24-28 hours, and for PT, aPTT and FVII:C at 48-52 hours. No statistically significant differences were seen for fibrinogen, antithrombin, or thrombin-antithrombin complexes (Friedman repeated measures analysis of variance). The present data suggest that the use of whole blood samples transported at ambient temperature may be an acceptable means of delivering specimens for coagulation analysis. With the exception of factor V and VIII coagulant activity, and total PS antigen all investigated parameters can be measured 24-28 hours after specimen collection without observing clinically relevant changes.     

Classification of non-union: need for a new scoring system?

SUMMARY: A new scoring system is proposed in order to assist surgeons with the complex analysis associated with non-union surgery. Patients with non-union are rarely easily compared with one another and this has frustrated research in this field. We have therefore attributed values to clinical features based on clinical experience and research evidence, so that patients of similar complexity can be compared with one another. When greater experience with this scoring system has been gained it will be further refined and validated. We propose that surgeons with a sub specialist interest in non-union surgery use this system in reporting results, and that non- specialist surgeons use it to inform their decision to treat the fracture themselves, or refer to a sub specialist.     

State and trait anxiety and depression in patients with primary brain tumors before and after surgery: 1-year longitudinal study

OBJECT: The aim in this study was to assess the state and trait types of anxiety as well as current depression before and after surgery in patients affected by brain tumors. The relationships between these affective disorders and the patient's sex, tumor histology, and laterality of the tumor were also evaluated. METHODS: A total of 72 patients affected by a primary brain tumor were enrolled in the study. Histological grades were assigned according to the World Health Organization classification. State and trait anxiety were assessed using the State and Trait Anxiety Inventory; current depression was assessed using the Zung Self-Rating Depression Scale. Cognitive impairment was assessed using the 10-item Short Portable Mental Status Questionnaire. Psychometric evaluation was assessed before surgery and at 1, 3, 6, and 12 months after surgery. RESULTS: Before brain surgery, 62.5% of patients showed state anxiety, 50% of patients showed trait anxiety, and 9.7% of patients showed current depression. During the follow-up period there was no significant variation in the percentage of patients with state anxiety (p=0.416) and trait anxiety (p=0.7), whereas a significant increase in the percentage of those with current depression was found (p<0.0001), in particular at 1 month (p=0.002) and 3 months (p=0.039) after surgical treatment. The tumor's laterality and histology showed no correlation with psychometric variables, whereas a relationship between the presence of trait anxiety at the enrollment and current depression after surgery (p<0.0001) was found. CONCLUSIONS: Patients affected by brain tumors frequently experience affective disorders. After brain surgery, a depressive state can develop. The psychometric assessment could be useful in these patients for quick recognition of psychological disorders.     

Biliary complications after liver transplantation from maastricht category-2 non-heart-beating donors

BACKGROUND: There are unresolved issues regarding the security of liver transplantation with non-heart-beating donors (NHBDs). Recently, an increased incidence of biliary complications, mainly intrahepatic ischemic-type biliary strictures, has been described after controlled NHBDs. METHODS: We studied the incidence and risk factors for biliary complications among uncontrolled NHBDs recipients compared with a large population of HBD recipients. RESULTS: Overall, 16.8% of patients in the HBD group and 41.7% of patients in the NHBD group suffered any type of biliary complication (P=0.66). However, the incidence of nonanastomotic biliary strictures was significantly greater in the NHBD group (P<0.001). Multivariate analysis showed that independent risk factors for nonanastomotic strictures were hepatic artery thrombosis (relative risk; 98.7) and receiving a liver from a NHBD (relative risk; 47.1). CONCLUSIONS: If this type of donors is accepted as a source of liver organs, the high incidence of biliary complications should be considered and efforts should be made to decrease ischemic injury.     

Comparison between titanium and anatase miRNAs regulation

Titanium is the gold standard among materials used for prosthetic devices because of its good mechanical and chemical properties. There are three allotropic forms of titanium dioxide: brookite, rutile, and anatase. Anatase can be prepared as a colloidal suspension and used to coat surfaces. Anatase coating (AC) can potentially have biological effects and specifically can induce bone formation. To obtain more information about the osteogenic effect of AC in comparison to to titanium we used microRNA (miRNA) microarray techniques to investigate the translation regulation in osteoblasts exposed to both titanium and AC. There were three upregulated miRNAs (mir-1, mir-34c, mir-210) and eight downregulated miRNAs (mir-23b, mir-377, mir-22, mir-93, mir-422b, mir-17-5p, mir-24, mir-130b) for false discovery rate = 0 and score >3. The data reported are relevant to understand the molecular mechanism of bone regeneration and as a model for comparing other materials with similar clinical effects.     

Combinatorial experimental protocols for Erbicin-derived immunoagents and Herceptin

Erbicin is a human anti-ErbB2 single-chain antibody fragment with high affinity and selectivity for ErbB2-positive cancer cells. Two anti-ErbB2 immunoconjugates, called Erb-hRNase and Erb-hcAb, have been prepared and found to be selectively cytotoxic on ErbB2-positive cancer cells in vitro and vivo. In Erb-hRNase, Erbicin is linked to a human RNase and in Erb-hcAb it is linked to the key structural and functional regions of a human IgG. Herceptin is an anti-ErbB2 humanised antibody successfully used in the immunotherapy of breast cancer. We report here that the Erbicin-derived immunoagents target on breast cancer cells an ErbB2 epitope different than that of Herceptin. This finding led us to verify the effects of Herceptin on breast cancer cells when it was used in combination with the Erbicin-derived immunoagents. The results indicated that in combination experiments the antitumour action of Herceptin and that of the novel agents were significantly increased in an additive fashion. An inspection of the mechanism of action of Erb-hRNase or Erb-hcAb combined with Herceptin provided evidence that the antibody combinations engendered an increased downregulation of the ErbB2 receptor, and led to an enhanced apoptotic cell death.     

Francesco Rizzoli (1809-1880) and the elusive case of Giulia: the description of an 'arteriovenous aneurysm passino through the wall of the skull'

The improved knowledge of clinical and emodynamical aspects of extracranial arteriovenous malformations in the 18 th century provided a foundation for the understanding and treatment of cerebrovascular pathology. It was not until the late 19 th century that detailed clinicopathological reports of intracranial arteriovenous malformations were published. In this historical context, a seminal report written by the Italian surgeon Francesco Rizzoli is worthy of notice, the Giulia case. A 9-year-old girl presenting with seizures and an occipital pulsanting swelling was examined in 1873 by Rizzoli. He was able to use Giulia's signs and symptoms to predict the complex angioarchitecture of her 'arteriovenous aneurysm passing through the wall of skull'. The postmortem dissection completely confirmed the supposed diagnosis, disclosing a direct communication between the hypertrophic branches of the ocipital artery and the transverse sinus. The clinical course of that case is briefly reviewed in this article and the diagnosis of this unusual arteriovenous shunt is discussed in light of the current neurosurgical knowledge.     

5-HT1A receptors are involved in the anxiolytic effect of Delta9-tetrahydrocannabinol and AM 404, the anandamide transport inhibitor, in Sprague-Dawley rats

The mechanism mediating the effects of cannabinoids on anxiety-related responses appear to involve cannabinoid CB1 and non-CB1 receptors. However, other neurotransmitters may play a role in such effect. This study shows evidence of an interaction between endocannabinoid system and serotonin (5-HT), 1A receptor subtype on anxiety-like behavior in Sprague-Dawley rats. The exogenous cannabinoid agonist, Delta9-tetrahydrocannabinol (THC), and N-(4-hydroxyphenyl)-arachidonylamide, the anandamide transporter inhibitor (AM 404) were evaluated in the elevated plus maze test. THC (0.075-0.75 mg/kg i.p.), given 30 min and AM 404 (0.75-1.25 mg/kg i. p.), given 60 min before the test, exhibited a dose-response anxiolytic effect evaluated in terms of increase in the percentage of total entries and time spent in the open and decrease of total entries and time spent in the closed arms. The anxiolytic effect obtained with the maximal active dose of both THC (0.75 mg/kg) and AM 404 (1.25 mg/kg) was blocked by the 5-HT1A receptor antagonist, N-[2-[4-(2-methoxyphenyl) piperazin-1-yl]ethyl]-N-pyridin-2-yl-cyclohexanecarboxamide dihydro chloride (WAY-100635 (300 microg/kg, s.c.), given 30 min before THC or 15 min before AM 404. The combination of an ineffective dose of THC (0.015 mg/kg) or AM 404 (0.015 mg/kg) on anxiety-related responses with an ineffective dose of the 5HT(1A) receptor agonist, 8-Hydroxy-2-(di-n-propylamino) tetralin hydrobromide (8-OH-DPAT) (7.5 microg/kg, i.p.), led to a synergistic effect. No interference with spontaneous motor activity, evaluated in an activity cage for 5 min, in rats given the drugs alone or in combination, was found. These data suggest that the anxiolytic effect produced by endo- and eso-cannabinoids is modulated by 5-HT1A receptors.