Fatal myocardial infarction after lung resection in a patient with prophylactic preoperative coronary stenting†

In this report we present the case of a 77-yr-old man who underwent resection of the upper lobe of the left lung for a carcinoma, six weeks after percutaneous transluminal coronary angioplasty (PTCA) with stenting of the left anterior descending (LAD) and circumflex coronary arteries. Antiplatelet therapy with clopidogrel was interrupted two weeks before surgery to allow for epidural catheter placement and to minimize haemorrhage. The surgical procedure was uneventful. In the immediate postoperative period, however, the patient suffered severe myocardial ischaemia. Emergency coronary angiography showed complete thrombotic occlusion of the LAD stent. In spite of successful recanalization, reinfarction occurred and the patient died in cardiogenic shock. Prophylactic preoperative coronary stenting may put the patient at risk of stent thrombosis if surgery cannot be postponed for three months. In such cases, other strategies such as perioperative β-blockade for preoperative cardiac management should be considered. Br J Anaesth 2004; 92: 743-

Influence of airway‐occluding instruments on airway pressure during jet ventilation for rigid bronchoscopy

We measured changes in airway pressure (Paw) caused by microsurgical instruments introduced into a rigid bronchoscope during high frequency jet ventilation (HFJV). With approval of the institutional Ethics Committee, 10 adults undergoing elective tracheobronchial endoscopy and endosonography during general anaesthesia were investigated. Inflation of an endosonography probe balloon in the left main stem bronchus caused airway obstruction. Pressure measurements proximal and distal to the obstruction were compared after three degrees of obstruction (0%, 50% and 90%) and with two different driving pressure settings. Airway obstruction increased the mean (sd) peak inspiratory pressure (PIP) from 7.5 (2.6) to 9.5 (3.5) mm Hg for 2 atm (P=0.0008) and from 9.7 (3.7) to 13.0 (5.1) mm Hg for 3 atm (P=0.0001). Airway obstruction did not alter peripheral PIP (7.2 (4.1) to 7.1 (3.7) mm Hg for 2 atm and 8.8 (4.3) to 9.4 (5.2) mm for 3 atm), but resulted in an end‐expiratory pressure (EEP) beyond the narrowing being significantly greater than in the unobstructed airway (2.5 (3.4) to 5.5 (3.7) mm Hg for 2 atm; P=0.0005) and 3.2 (3.6) to 8.0 (4.3) mm for 3 atm; P<0.0001). Severe airway narrowing increases inspiratory pressure proximal and expiratory pressure distal to the obstruction in relation to the applied driving pressure. Since the distal EEP never exceeded PIP, even near‐total airway obstruction should not cause severe lung distension or barotrauma in subjects with normal lungs. Br J Anaesth 2000; 85: 463-

Effect of rofecoxib on platelet aggregation and blood loss in gynaecological and breast surgery compared with diclofenac

Background. Non‐selective cyclooxygenase (COX) inhibitors or non‐steroidal anti‐ inflammatory drugs (NSAIDs) are frequently omitted for perioperative pain relief because of potential side‐effects. COX‐2‐selective inhibitors may have a more favourable side‐effect profile. This study tested the hypothesis that the COX‐2‐selective inhibitor rofecoxib has less influence on platelet function than the NSAID diclofenac in gynaecological surgery. In addition, analgesic efficacy and side‐effects of the two drugs were compared. Methods. In this single‐centre, prospective, double‐blind, active controlled study, women undergoing vaginal hysterectomy (n=25) or breast surgery (n=25) under general anaesthesia received preoperatively 50 mg of rofecoxib p.o. followed 8 and 16 h later by two doses of placebo or three doses of diclofenac 50 mg p.o. at the same time points. We assessed arachidonic acid‐stimulated platelet aggregation before and 4 h after the first dose of study medication, estimated intraoperative blood loss, and haemoglobin loss until the first morning after surgery. Analgesic efficacy, use of rescue analgesics, and side‐effects were also recorded. Results. In the rofecoxib group, stimulated platelet aggregation was disturbed less (P=0.02), and estimated intraoperative blood loss (P=0.01) and the decrease in haemoglobin were lower (P=0.01). At similar pain ratings, the use of anti‐emetic drugs was less in the rofecoxib group (P=0.03). Conclusion. Besides having a smaller effect on platelet aggregation, one oral dose of rofecoxib 50 mg given before surgery provided postoperative analgesia similar to that given by three doses of diclofenac 50 mg and was associated with less use of anti‐emetics and less surgical blood loss in gynaecological surgery compared with diclofenac. Br J Anaesth 2004; 92: 523-3

Nat Struct Mol Biol

Internal ribosome entry sites (IRESs) facilitate an alternative, end-independent pathway of translation initiation. A particular family of dicistroviral IRESs can assemble elongation-competent 80S ribosomal complexes in the absence of canonical initiation factors and initiator transfer RNA. We present here a cryo-EM reconstruction of a dicistroviral IRES bound to the 80S ribosome. The resolution of the cryo-EM reconstruction, in the subnanometer range, allowed the molecular structure of the complete IRES in its active, ribosome-bound state to be solved. The structure, harboring three pseudoknot-containing domains, each with a specific functional role, shows how defined elements of the IRES emerge from a compactly folded core and interact with the key ribosomal components that form the A, P and E sites, where tRNAs normally bind. Our results exemplify the molecular strategy for recruitment of an IRES and reveal the dynamic features necessary for internal initiation

Structure of the mammalian ribosome as it decodes the selenocysteine UGA codon

The elongation of eukaryotic selenoproteins relies on a poorly understood process of interpreting in-frame UGA stop codons as selenocysteine (Sec). We used cryo-electron microscopy to visualize Sec UGA recoding in mammals. A complex between the noncoding Sec-insertion sequence (SECIS), SECIS-binding protein 2 (SBP2), and 40S ribosomal subunit enables Sec-specific elongation factor eEFSec to deliver Sec. eEFSec and SBP2 do not interact directly but rather deploy their carboxyl-terminal domains to engage with the opposite ends of the SECIS. By using its Lys-rich and carboxyl-terminal segments, the ribosomal protein eS31 simultaneously interacts with Sec-specific transfer RNA (tRNASec) and SBP2, which further stabilizes the assembly. eEFSec is indiscriminate toward l-serine and facilitates its misincorporation at Sec UGA codons. Our results support a fundamentally distinct mechanism of Sec UGA recoding in eukaryotes from that in bacteria

Self-diffusion in granular gases

The coefficient of self-diffusion for a homogeneously cooling granular gas changes significantly if the impact-velocity dependence of the restitution coefficient $\epsilon$ is taken into account. For the case of a constant $\epsilon$ the particles spread logarithmically slow with time, whereas the velocity dependent coefficient yields a power law time-dependence. The impact of the difference in these time dependences on the properties of a freely cooling granular gas is discussed.Comment: 6 pages, no figure

Localized and Cellular Patterns in a Vibrated Granular Layer

We propose a phenomenological model for pattern formation in a vertically vibrated layer of granular material. This model exhibits a variety of stable cellular patterns including standing rolls and squares as well as localized objects (oscillons and worms), similar to recent experimental observations(Umbanhowar et al., 1996). The model is an amplitude equation for the parametrical instability coupled to the mass conservation law. The structure and dynamics of the solutions resemble closely the properties of localized and cellular patterns observed in the experiments.Comment: 4 pages, 4 figures, submitted to Phys. Rev. Let

Cooling dynamics of a dilute gas of inelastic rods: a many particle simulation

We present results of simulations for a dilute gas of inelastically colliding particles. Collisions are modelled as a stochastic process, which on average decreases the translational energy (cooling), but allows for fluctuations in the transfer of energy to internal vibrations. We show that these fluctuations are strong enough to suppress inelastic collapse. This allows us to study large systems for long times in the truely inelastic regime. During the cooling stage we observe complex cluster dynamics, as large clusters of particles form, collide and merge or dissolve. Typical clusters are found to survive long enough to establish local equilibrium within a cluster, but not among different clusters. We extend the model to include net dissipation of energy by damping of the internal vibrations. Inelatic collapse is avoided also in this case but in contrast to the conservative system the translational energy decays according to the mean field scaling law, E(t)\propto t^{-2}, for asymptotically long times.Comment: 10 pages, 12 figures, Latex; extended discussion, accepted for publication in Phys. Rev.

Structures of active melanocortin-4 receptor−Gs-protein complexes with NDP-α-MSH and setmelanotide

The melanocortin-4 receptor (MC4R), a hypothalamic master regulator of energy homeostasis and appetite, is a class A G-protein-coupled receptor and a prime target for the pharmacological treatment of obesity. Here, we present cryo-electron microscopy structures of MC4R–Gs-protein complexes with two drugs recently approved by the FDA, the peptide agonists NDP-α-MSH and setmelanotide, with 2.9 Å and 2.6 Å resolution. Together with signaling data from structure-derived MC4R mutants, the complex structures reveal the agonist-induced origin of transmembrane helix (TM) 6-regulated receptor activation. The ligand-binding modes of NDP-α-MSH, a high-affinity linear variant of the endogenous agonist α-MSH, and setmelanotide, a cyclic anti-obesity drug with biased signaling toward Gq/11, underline the key role of TM3 in ligand-specific interactions and of calcium ion as a ligand-adaptable cofactor. The agonist-specific TM3 interplay subsequently impacts receptor–Gs-protein interfaces at intracellular loop 2, which also regulates the G-protein coupling profile of this promiscuous receptor. Finally, our structures reveal mechanistic details of MC4R activation/inhibition, and provide important insights into the regulation of the receptor signaling profile which will facilitate the development of tailored anti-obesity drugs