Safer, more expensive iodinated contrast agents: how do we decide?

The advantages of the new, safer, but more expensive iodinated contrast agents are discussed, and opinions on which patient groups should receive the agents are presented.     

抗胆碱药3-(2-苯基-2-环戊基-2-羟基-乙氧基)奎宁环烷的立体化学和构效关系

研究了强效抗胆碱药dl-3-(2-苯基-2-环戊基-2-羟基-乙氧基)-奎宁环烷的四个光学异构体的两种不对称合成方法,用HPLC检测了异构体含量,讨论了构效关系。     

Fracture frequency of all-ceramic crowns during dynamic loading in a chewing simulator using different loading and luting protocols

OBJECTIVE: The purpose of this laboratory study was to compare the frequency of failures (complete fractures or partial cracks) of molar crowns made of two different all-ceramic materials during dynamic loading in a chewing simulator, as well as the fracture load when subjected to static loading, in relation to different dynamic loading and luting protocols. METHODS: One hundred and forty-four molar crowns fabricated with IPS Empress or an experimental e.max Press material with high translucency (e.max Press Exp) were luted on CAD/CAM milled PMMA abutments (first lower molar, circular chamfer) either with Variolink or glass-ionomer cement (GIC). All crowns were loaded according to three different loading protocols (n=12 per group) and two force profiles (sinusoidal, rectangular) in a pneumatically driven chewing simulator with a steel stylus (? 8mm) and they underwent simultaneous thermocycling (5 degrees C/55 degrees C). After each phase the crowns were evaluated with regard to fractures or cracks. After dynamic testing, the crowns that did not fail were subjected to compression loading until complete fracture in a universal testing machine (UTM). As control groups, unloaded crowns were also subjected to a UTM. Survival statistics with log-rank tests were applied for the results of the dynamic loading, while ANOVA with post hoc Tukey B was used for the fracture load results and two-way ANOVA was carried out for logarithmically transformed data. Weibull statistics were calculated for pooled fracture load data of the dynamically loaded and control groups. RESULTS: In the 144 IPS Empress crowns, complete fractures were observed in 9 crowns and partial cracks in another 3 crowns. When the data was pooled, a statistically significant increase in fractures occurred when the sinusoidal force profile was applied compared to a rectangular force profile (log-rank, p<0.05). No fractures occurred in the e.max Press Exp crowns. The two-way ANOVA showed that the type of luting protocol used had the most significant effect on the fracture load of both materials. In conjunction with Empress, however, the luting material influenced the variability twice as much as in e.max Press Exp. There was no statistically significant difference in the fracture load of GIC-luted e.max Press Exp crowns and that of the Variolink luted Empress crowns. The force profile had a significant effect on the fracture load only of the Empress crowns but not of the e.max Press Exp crowns. Weibull statistics revealed a higher scattering of the data of dynamically loaded crowns compared to that of the control groups. CONCLUSIONS: For testing all-ceramic materials, dynamic loading is indispensable to draw valid conclusions on clinical performance of all-ceramic molar crowns. A sinusoidal profile is advisable, while a gradual increase of the force amplitude does not significantly affect the results.     

Pulmonary artery catheterization: a modified technique

A modified technique for catheterization of the pulmonary artery was developed. It involves the passage of a tapered, movable-core, J-tipped guide wire across the right ventricle into the pulmonary artery followed by the advancement of a straightened Grollman pigtail catheter. The technique was successful in 34 of 34 pulmonary artery catheterizations. The method avoids prolonged catheter manipulation within the right ventricle. In addition, since the catheter does not cross the tricuspid valve until the guide wire has been advanced, the occasional complication of the pigtail "hooking" on a tricuspid valve leaflet or chordae tendineae during catheter withdrawal and manipulation is prevented.     

Identifying candidate causal variants responsible for altered activity of the ABCB1 multidrug resistance gene

The difficulty of fine localizing the polymorphisms responsible for genotype-phenotype correlations is emerging as an important constraint in the implementation and interpretation of genetic association studies, and calls for the definition of protocols for the follow-up of associated variants. One recent example is the 3435C>T polymorphism in the multidrug transporter gene ABCB1, associated with protein expression and activity, and with several clinical conditions. Available data suggest that 3435C>T may not directly cause altered transport activity, but may be associated with one or more causal variants in the poorly characterized stretch of linkage disequilibrium (LD) surrounding it. Here we describe a strategy for the follow-up of reported associations, including a Bayesian formalization of the associated interval concept previously described by Goldstein. We focus on the region of high LD around 3435C>T to compile an exhaustive list of variants by (1) using a relatively coarse set of marker typings to assess the pattern of LD, and (2) resequencing derived and ancestral chromosomes at 3435C>T through the associated interval. We identified three intronic sites that are strongly associated with the 3435C>T polymorphism. One of them is associated with multidrug resistance in patients with epilepsy (chi2 = 3.78, P = 0.052), and sits within a stretch of significant evolutionary conservation. We argue that these variants represent additional candidates for influencing multidrug resistance due to P-glycoprotein activity, with the IVS 26+80 T>C being the best candidate among the three intronic sites. Finally, we describe a set of six haplotype tagging single-nucleotide polymorphisms that represent common ABCB1 variation surrounding 3435C>T in Europeans.     

乳腺管状小叶癌

乳腺管状小叶癌（Tubulolobular carcinoma，TLC）最初是被作为小叶癌的管状变型。作者总结了27例TLC的组织学、免疫表型和临床特征，并与纯小管癌和经典型小叶癌进行了比较。此组患者年龄43-79岁（中位年龄60岁）。1例双侧乳腺受累，5例病变为多灶性。肿瘤直径0．5-2．5cm，色灰褐，质硬。组织学观察：TLC的肿瘤细胞形成管状和条索状两种结构模式并相互混杂，且两者比例相当（统称为管状小叶模式）。     

Proceedings of the Symposium ‘Angiotensin AT1 Receptors: From Molecular Physiology to Therapeutics’: PHYSIOLOGICAL ACTIONS OF ANGIOTENSIN II MEDIATED BY AT1 AND AT2 RECEPTORS IN THE BRAIN

• 1 Autoradiographic binding studies have shown that the AT₁ receptor is the predominant angiotensin II (AngII) receptor subtype in the central nervous system (CNS). Major sites of AT₁ receptors are the lamina terminalis, hypothalamic paraventricular nucleus, the lateral parabrachial nucleus, rostral and caudal ventrolateral medulla, nucleus of the solitary tract and the intermediolateral cell column of the thoraco-lumbar spinal cord.
• 2 While there are differences between species, AT₂ receptors are found mainly in the cerebellum, inferior olive and locus coeruleus of the rat.
• 3 Circulating AngII acts on AT₁ receptors in the subfornical organ and organum vasculosum of the lamina terminalis (OVLT) to stimulate neurons that may have a role in initiating water drinking.
• 4 Centrally administered AngII may act on AT₁ receptors in the median preoptic nucleus and elsewhere to induce drinking, sodium appetite, a sympathetic vasoconstrictor response and vasopressin secretion.
• 5 Recent evidence shows that centrally administered AT₁ antagonists inhibit dipsogenic, natriuretic, pressor and vasopressin secretory responses to intracerebroventricular infusion of hypertonic saline. This suggests that an angiotensinergic neural pathway has a role in osmoregulatory responses.
• 6 Central angiotensinergic pathways which include neural inputs to the rostral ventrolateral medulla may use AT₁ receptors and play a role in the function of sympathetic pathways maintaining arterial pressure.