Active site-blocked factor Xa prevents thrombus formation in the coronary vasculature in parallel with inhibition of extravascular coagulation in a canine thrombosis model

Factor Xa is a central procoagulant enzyme, linking the intrinsic and extrinsic activation mechanisms to the final common pathway of coagulation. To assess its contribution to pathologic thrombosis, studies were performed in a canine coronary thrombosis model. Thrombus formation was initiated by the application of electric current via a needle electrode placed in the lumen of the left circumflex coronary artery. When 50% occlusion of the vessel developed, the current was stopped and animals received an intravenous bolus of either saline, bovine glutamyl-glycinyl-arginyl-factor Xa (Xai), a competitive inhibitor of factor Xa assembly into the prothrombinase complex, Factor X, or heparin. Animals infused with saline or factor X (300 micrograms/kg) developed total occlusion of the vessel due to a fibrin/platelet thrombus in 70 +/- 11 minutes (36 of 36 animals) and 74 +/- 13 minutes (8 of 8 animals), respectively. In contrast, infusion of Xai prevented thrombus formation completely at a dose of 300 micrograms/kg (8 of 8 animals). As the dose of Xai was decreased, its antithrombotic effect was diminished, with a patency rate of only 2 of 6 animals at a dose of 90 micrograms/kg. Xai at 300 micrograms/kg prevented the accumulation of 125I-fibrinogen/fibrin at the site of the coronary thrombus by approximately 63% and decreased deposition of 111In-labeled platelets by approximately 57%. Hemostatic parameters of animals infused with Xai demonstrated prolongation of the PT and dose- dependent increased extravascular bleeding tendency. These data indicate that factor Xa has a comparably important role in thrombus formation and extravascular hemostasis, and contrast with previous results in this same animal model in which IXai selectively prevented clotting in the coronary vasculature.     

The role of pancreatic venous sampling in the localization of occult insulinomas

The palpation and enucleation of occult insulinomas (less than 15 mm) can be a difficult surgical problem even with good arteriographic localization. In the authors' limited experience, confirmation of arteriographic findings by pancreatic venous sampling provided little additional localizing information. However, if arteriography is negative or equivocal, venous sampling can indicate the segment of pancreas to be "blindly" resected if the adenoma is not palpable. Venous sampling may be misleading in polyendocrine syndromes because of the frequency of multiple adenomas and variable hormone production.     

Nucleic Acids and Cytological Changes in the Thyroid Gland after Thiouracil.l

1) By the action of thiouracil the follicular cell is not brought into the state of physiological inactivity and it shows signs of apparent secretion which differ however in details remarkably from the effective secretion stage. 2.) The quantity of follicular cells in mitosis is temporarily increased to the multiple. This disturbance is the result of the inhibition of caryokinesis in the stage of metaphase. 3) The absolute quantities of ribonucleic and of desoxyribonu-cleic acid are considerably reduced. 4) The ratio KNA/DNA shows a decrease to a fractional part of the normal value, according to the increase of the cell mass.     

Left ventricular volumes measured by MR imaging

We assessed the potential of proton magnetic resonance (MR) imaging for accurately measuring left ventricular volumes using 15 latex casts of excised human left ventricles. The casts were submerged in water to stimulate the endocardial left ventricular cavity interface in in vivo imaging conditions. Tomographic image sections perpendicular to the long axis of the cast were obtained, spanning each cast from apex to base. Simpson's rule was used to calculate the cast volumes. Correlation between the actual cast volumes (as measured by the displacement method) and the calculated volumes using MR imaging for the 15 casts was excellent. Our data demonstrate that MR imaging accurately measures cardiac chamber volumes in this in vitro model.     

Congenital chylothorax: from foetal life to adolescence

Aim: To analyse the main prenatal and postnatal features of congenital chylothorax (CC), and the outcome including mid‐term follow‐up. Methods: We searched our databases for CC diagnosed between 1990 and 2006. Data of 29 cases were retrieved and analysed. Follow‐up until 3 years of age was available for all patients. Results: Most patients were diagnosed prenatally (94%) and most cases were complicated by foetal hydrops (66.7%). The overall survival rate at 3 years was 56%. A significantly poorer outcome was observed when foetal hydrops, preterm birth < 34 weeks, large effusions and/or early‐onset pneumothorax were present. An important but not significant improvement in the survival rate was observed through the study period; while in 1990–1998, the survival rate was 41.7%, from 1999 to 2006 it was 66.7% (p = 0.19). In the mid‐term follow‐up, we did not observe any recurrence of CC and most infants remain asymptomatic. However, 27% of survivors were diagnosed as having asthma in early infancy. Conclusion: CC still carries a significant risk of perinatal mortality. However, continuous advances in foetal and neonatal medicine are improving the prognosis of these patients, and nowadays most of them are likely to survive. Beyond the neonatal period, most survivors have an uneventful outcome.     

慢性硬膜下血肿168例的诊治和预后

0　引言　 1 992 - 0 5～ 1 999- 0 5我科收治慢性硬膜下血肿 (CS-DH) 1 6 8例 ,其中 1 6 4例经颅骨钻孔冲洗引流术治疗 ,4例保守治疗 ,结果 1 6 5例治愈 ,3例死亡 .结论 :CSDH的诊断主要依靠 CT检查 ,手术简单 ,防止并发症可改善预后 .1　临床资料　男 1 6 3例 ,女 5例 ,年龄 32～ 79岁 ,平均 5 4岁 .有明确的外伤史 1 4 5例 (86 .3% ) ,原因不明 2 3例(1 3.7% ) ,病程 3wk～ 6 a.头昏、头痛、呕吐 1 1 6例 ,肢体运动障碍 6 8例 ,智力及精神障碍 46例 ,语言障碍 1 0例 ,感觉障碍2 1例 ,排尿障碍 5例 ,癫痫 3例 ,视乳头水肿 92例 ,锥体…     

Rethinking parenting interventions for drug-dependent mothers: from behavior management to fostering emotional bonds

Mothers who are physically and/or psychologically dependent upon alcohol and illicit drugs are at risk for a wide range of parenting deficits beginning when their children are infants and continuing as their children move through school-age and adolescent years. Behavioral parent training programs for drug-dependent mothers have had limited success in improving parent-child relationships or children's psychological adjustment. One reason behavioral parenting programs may have had limited success is the lack of attention to the emotional quality of the parent-child relationship. Research on attachment suggests that the emotional quality of mother-child relationships is an important predictor of children's psychological development through school-age and adolescent years. In this paper, we present a rationale and approach for developing attachment-based parenting interventions for drug-dependent mothers and report preliminary data on the feasibility of offering an attachment-based parenting intervention in an outpatient drug treatment program for women.     

Striatal structure and its association with N-Acetylaspartate and glutamate in autism spectrum disorder and obsessive compulsive disorder

Autism spectrum disorders (ASD) and obsessive compulsive disorder (OCD) are often comorbid and are associated with changes in striatal volumes and N-Acetylaspartate (NAA) and glutamate levels. Here, we investigated the relation between dorsal striatal volume and NAA and glutamate levels. We additionally compared striatal volume and shape between ASD, OCD and controls. T1-weighted magnetic resonance (MR) images, proton spectra (1H-MRS) in the left striatum, and phenotypic information were collected from 54 children with ASD, 32 with OCD, and 56 controls (aged 8–13 years) in a four-site study. Dorsal striatal volume and shape were determined using the FMRIB integrated registration and segmentation tool (FIRST). Spectra were processed with Linear Combination Model. The relationship of left striatal volume with NAA and glutamate was investigated, and group comparisons were performed for NAA levels and for bilateral striatal volume and shape. NAA levels were lower in subjects with ASD compared with controls (t=2.86, p=0.005) and were associated with striatal volume (β=0.37, t=2.78, p=0.008). Glutamate levels were also associated with volume in the ASD group (β=0.38, t=2.46, p=0.018). No group differences were found for striatal volume or shape, but a post-hoc diagnosis-by-hemisphere interaction (F_(2,129)=3.86, p=0.024) revealed greater asymmetry (right>left) in striatal volume for the disorder-groups compared with controls. Our findings show involvement of NAA and glutamate in striatal volume in ASD and suggest greater asymmetry in paediatric ASD and OCD compared with controls, pointing to overlapping subcortical abnormalities. The lower NAA in ASD reflects reduced neuronal integrity or impaired neuronal functioning.     

Micronucleus test in mussels Perna perna fed with the toxic dinoflagellate Prorocentrum lima

Micronucleus (MN) and other nuclear abnormalities have been measured in the hemocytes of mussels Perna perna to verify whether feeding mussels with different concentrations of Prorocentrum lima results in accumulation of levels of okadaic acid (OA) capable of inducing genotoxic effects at the chromosome level, as evidenced by micronuclei and nuclear abnormalities. Four groups of 12 mussels housed individually in aquaria containing filtered seawater were fed with different concentrations of P. lima. Another group collected directly from the production area served as outdoor control. A significantly higher frequency of MN and nuclear lesions was observed in hemocytes from the groups fed P. lima.     

Modulation of gastrointestinal function by MuDelta,a mixed μ opioid receptor agonist/ μ opioid receptor antagonist

BACKGROUND & PURPOSE

Loperamide is a selective µ opioid receptor agonist acting locally in the gastrointestinal (GI) tract as an effective anti-diarrhoeal but can cause constipation. We tested whether modulating µ opioid receptor agonism with δ opioid receptor antagonism, by combining reference compounds or using a novel compound (‘MuDelta’), could normalize GI motility without constipation.

EXPERIMENTAL APPROACH

MuDelta was characterized in vitro as a potent µ opioid receptor agonist and high-affinity δ opioid receptor antagonist. Reference compounds, MuDelta and loperamide were assessed in the following ex vivo and in vivo experiments: guinea pig intestinal smooth muscle contractility, mouse intestinal epithelial ion transport and upper GI tract transit, entire GI transit or faecal output in novel environment stressed mice, or four weeks after intracolonic mustard oil (post-inflammatory). Colonic δ opioid receptor immunoreactivity was quantified.

KEY RESULTS

δ Opioid receptor antagonism opposed µ opioid receptor agonist inhibition of intestinal contractility and motility. MuDelta reduced intestinal contractility and inhibited neurogenically-mediated secretion. Very low plasma levels of MuDelta were detected after oral administration. Stress up-regulated δ opioid receptor expression in colonic epithelial cells. In stressed mice, MuDelta normalized GI transit and faecal output to control levels over a wide dose range, whereas loperamide had a narrow dose range. MuDelta and loperamide reduced upper GI transit in the post-inflammatory model.

CONCLUSIONS AND IMPLICATIONS

MuDelta normalizes, but does not prevent, perturbed GI transit over a wide dose-range in mice. These data support the subsequent assessment of MuDelta in a clinical phase II trial in patients with diarrhoea-predominant irritable bowel syndrome.