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.     

A cross-specialty survey to assess the application of risk stratified surgery for differentiated thyroid cancer in the UK

Introduction

This study describes variability of treatment for differentiated thyroid cancer among thyroid surgeons, in the context of changing patterns of thyroid surgery in the UK.

Methods

Hospital Episodes Statistics on thyroid operations between 1997 and 2012 were obtained for England. A survey comprising six scenarios of varying ‘risk’ was developed. Patient/tumour information was provided, with five risk stratified or non-risk stratified treatment options. The survey was distributed to UK surgical associations. Respondent demographics were categorised and responses analysed by assigned risk stratified preference.

Results

From 1997 to 2012, the Hospital Episode Statistics data indicated there was a 55% increase in the annual number of thyroidectomies with a fivefold increase in otolaryngology procedures and a tripling of cancer operations. Of the surgical association members surveyed, 264 respondents reported a thyroid surgery practice. Management varied across and within the six scenarios, and was not related consistently to the level of risk. Associations were demonstrated between overall risk stratified preference and higher volume practice (>25 thyroidectomies per year) (p=0.011), fewer years of consultant practice (p=0.017) and multidisciplinary team participation (p=0.037). Logistic regression revealed fewer years of consultant practice (odds ratio [OR]: 0.96/year in practice, 95% confidence interval [CI]: 0.922–0.997, p=0.036) and caseload of >25/year (OR 1.92, 95% CI: 1.044–3.522, p=0.036) as independent predictors of risk stratified preference.

Conclusions

There is a substantial contribution to thyroid surgery in the UK by otolaryngology surgeons. Adjusting management according to established case-based risk stratification is not widely applied. Higher caseload was associated with a preference for management tailored to individual risk.     

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.     

Strangulation in child abuse: CT diagnosis

The central nervous system is commonly affected in child abuse. Between April 1985 and July 1986 three infants were identified in whom the primary mode of injury had been strangulation. In each case computed tomography (CT) demonstrated a large cerebral infarction confined to vascular territories associated with small subdural hematomas. There was no history or visible evidence of significant head trauma. Autopsy of one infant confirmed the presence of a hemispheric infarct, thin subdural hematoma, and an area of subintimal hemorrhage in the carotid artery ipsilateral to the infarct. The remaining two patients survived with residual hemiparesis. CT findings of a large cerebral infarction with an associated subdural hematoma in an infant without a history of a significant trauma should suggest the possibility of child abuse and may be the primary manifestation of abuse in some patients.     

Incidence of red cell antibodies after multiple blood transfusion

A retrospective study was performed to estimate the frequency of alloimmunization against red cell (RBC) antigens in a multiply transfused group. Patients (n = 186) were studied who had received at least six blood transfusions during a period of at least 3 months. Some 6944 units of blood were transfused. One hundred forty patients had hematologic disorders. The patients' sera were investigated every 3 months with indirect antiglobulin tests and enzyme-treated RBCs. Twenty-two patients (11.8%) made 33 antibodies. Seven patients made more than one antibody. Eight of the 22 patients (36.4%) made their first antibody before or at the 10th transfusion. The risk of immunization increased with the number of transfusions. Influence of gender and age was not demonstrable. Nor was a relationship demonstrated between blood transfusion reactions and RBC antibody formation; no delayed hemolytic transfusion reactions occurred. Anti-E was demonstrated in 12 patients and anti-K in 15. When the gene frequencies were taken into account, it appeared that anti-E was made by 11.5 percent of E-negative patients, most of whom were immunized after an estimated three transfusions with E-positive blood. Anti-K was made by 8.7 percent of the K-negative patients, after an estimated 2.1 units of K-positive blood. It might be desirable to match red cell units for the E and K antigens in patients at relatively high risk. These are primarily patients who have already formed an antibody and are going to receive many transfusions and women of childbearing age who are to receive more than 4 units of blood.     

Iron stimulates the rate of reduction of hexavalent chromium by human microsomes

The NADPH-dependent reduction of chromium (VI), a known carcinogen, by hepatic microsomes was very similar for all five humans examined, with an apparent Km for chromate of 1.04-1.68 microM, and a Vmax of 10.4- 10.7 nmol/min/mg protein. Inhibitor studies indicate no role for cytochrome P450s, but a prominent role for flavoproteins, which could include P450 reductase, flavin-containing mono-oxygenase and cytochrome b5. Relative to anaerobic conditions, Cr(VI) reduction was inhibited only 26-37% by room air, which indicates that human microsomal Cr(VI) reduction could still proceed at significant rates, even in tissues with high O2 tensions. Studies with lung microsomes from one human exhibited Vmax and Km values that were two-thirds lower and 2.8-fold greater, respectively, than those of hepatic microsomes from the same individual; other Cr(VI)-reducing parameters were similar for lung and liver. Various forms of exogenous iron, when present at 0.76-6.3 microM, markedly enhanced both liver and lung microsomal rates and Vmax of Cr(VI) reduction, but did not significantly alter the other Cr(VI)- reducing parameters (Km, effects of O2 and inhibitors). These iron levels were 3.1- to 26-fold lower than the initial Cr(VI) concentration, which suggests that iron is serving a catalytic role. The ratio of human microsomal Cr(VI) reduction rates under aerobic versus anaerobic conditions remained fairly constant, regardless of iron concentration. Small increases in intracellular iron could therefore lead to large increases in the rate and extent of microsomal Cr(VI) reduction. Individuals that are simultaneously exposed to Cr(VI) and to agents that increase intracellular iron could therefore be at potentially greater risk for Cr(VI) toxicity and carcinogenicity.