CEREBROVASCULAR CARBON DIOXIDE REACTIVITY DURING EXPOSURE TO EQUIPOTENT ISOFLURANE AND ISOFLURANE IN NITROUS OXIDE ANAESTHESIA

We have studied the effects of hypocapnia on cerebrovascular changes in two MAC-equivalent anaesthetic regimens, using the transcranial Doppler technique as an index of cerebral blood flow (CBF) in 24healthy ASA I patients undergoing spinal surgery. Eight of the patients were subjected to carbon dioxide reactivity challenges in the awake state. Before surgery, the other 16 patients received, in random order, either 1.15% isoflurane in oxygen or 0.5% isoflurane with 70% nitrous oxide. Carbon dioxide reactivity was calculated for each group as the increase in flow velocity per kPa change in PÉCO2 (cm s−1 kPa−1). It was significantly greater for the isoflurane group (14.09 (SD 2.44) cm s−1 kPa−1) and significantly less for the isoflurane—nitrous oxide group (7.95 (1.32) cm s-−1 kPa−1) compared with the awake group (11.24 (0.95) cm s−1 kPa−1). We conclude that cerebrovascular responsiveness to changes in arterial carbon dioxide concentration is influenced markedly by the anaesthetic procedure. Hyperventilation is more likely to affect CBF during isoflurane anaesthesia than during an MAC-equivalent isoflurane—nitrous oxide anaesthesi

Recurrent post‐partum seizures after epidural blood patch

There are many causes for headaches after childbirth. Even though postdural puncture headache (PDPH) has to be considered in a woman with a history of difficult epidural anaesthesia, pre‐eclampsia should always be excluded as an important differential diagnosis. We report a case with signs of late‐onset pre‐eclampsia where administration of an epidural blood patch (EBP) was associated with eclampsia. A hypothetical causal relationship between the EBP and seizures was discarded on the basis of evidence presented in this report. Br J Anaesth 2003; 90: 247-5

Diagnostisches und therapeutisches Vorgehen in der Akutphase nach kranio-zervikalem Beschleunigungstrauma (sog. Schleudertrauma) : Empfehlungen einer schweizerischen Arbeitsgruppe

https://digitalrepository.unm.edu/abq_eh_news/1514/thumbnail.jp

Evaluation of a prostate cancer e-health-tutorial

Hintergrund: Angesichts verschiedener Behandlungsoptionen ist die Information und Therapieentscheidung beim lokalisierten Prostatakarzinom eine Herausforderung. Die digitale Informationstechnologie bietet im Vergleich zu gedruckten Informationen mehr Möglichkeiten, die Information und die Patientenkommunikation bedarfsgerecht zu gestalten. Ziele: Zur Unterstützung der Therapieentscheidung und der Kommunikation mit Patienten ist in der deutschsprachigen Schweiz ein Online-Tutorial in einem systematischen Prozess entwickelt und in einer Pilotstudie getestet worden. In der Evaluation interessierten die Nutzerzufriedenheit, die Erfüllung der Informationsbedürfnisse, die Vorbereitung auf die Therapieentscheidung und deren subjektive Qualität. Material und Methoden: Die Plattform wurde in einem iterativen Prozess mittels Fokusgruppen mit Ärzten und Patienten auf der Grundlage von Informationen aus bestehenden Broschüren entwickelt. Für den Test der Plattform wurden in 8 urologischen Kliniken 87 Patienten zur Teilnahme eingeladen. Die 56 Nutzer wurden 4 Wochen nach dem Login und 3 Monate nach dem Therapieentscheid online befragt, 48 Nutzer füllten beide Befragungen aus. Eingesetzte Instrumente waren die Preparation for Decision Making Scale (PDMS), die Decisional Conflict Scale (DCS) und die Decisional Regret Scale (DRS). Ergebnisse und Diskussion: Die Nutzenden sind mit der Plattform sehr zufrieden und finden ihre Informationsbedürfnisse gut erfüllt. Sie zeigen 3 Monate nach dem Entscheid eine gute Vorbereitung auf die Entscheidung (MW PDMS 75, SD 23) und berichten über niedrigen Entscheidungskonflikt (MW DCS 9.6, SD 11) und kaum Bedauern über die Entscheidung (MW DRS 6.4, SD 9.6). Basierend auf diesen Erkenntnissen kann die Plattform zur weiteren Nutzung empfohlen werden.Background: Due to the multitude of therapy options the treatment decision after diagnosis of a localised prostate cancer is challenging. Compared to printed booklets, web based information technology offers more possibilities to tailor information to patients’ individual needs. Objectives: To support the decision making process as well as the communication with patients we developed an online tutorial in a systematic process in the German speaking part of Switzerland and then tested it in a pilot study. The study investigated users’ satisfaction, the coverage of information needs, the preparation for decision making and the subjective quality of the decision. Materials and methods: Based on already existing information material the online tutorial was developed in an iterative process using focus groups with patients and urologists. For the following evaluation in eight clinics a total of 87 patients were invited to access the platform and participate in the study. From these patients 56 used the tutorial and 48 answered both surveys (the first one 4 weeks after the first login and the second one 3 months after treatment decision). The surveys used the Preparation for Decision Making Scale (PDMS), the Decisional Conflict Scale (DCS), and the Decisional Regret Scale (DRS). Results and Conclusion: Satisfaction with the tutorial is very high among patients with newly diagnosed localized prostate cancer. Users find their information needs sufficiently covered. Three months after the decision they felt that they were well prepared for the decision making (Mean PDMS 75, SD 23), they had low decisional conflict (Mean DCS 9.6, SD 11) and almost no decisional regret (Mean DRS 6.4, SD 9.6). Based on these findings the further use of the tutorial can be recommended

Immunoelectron Microscopic Evidence for Tetherin/BST2 as the Physical Bridge between HIV-1 Virions and the Plasma Membrane

Tetherin/BST2 was identified in 2008 as the cellular factor responsible for restricting HIV-1 replication at a very late stage in the lifecycle. Tetherin acts to retain virion particles on the plasma membrane after budding has been completed. Infected cells that express large amounts of tetherin display large strings of HIV virions that remain attached to the plasma membrane. Vpu is an HIV-1 accessory protein that specifically counteracts the restriction to virus release contributed by tetherin. Tetherin is an unusual Type II transmembrane protein that contains a GPI anchor at its C-terminus and is found in lipid rafts. The leading model for the mechanism of action of tetherin is that it functions as a direct physical tether bridging virions and the plasma membrane. However, evidence that tetherin functions as a physical tether has thus far been indirect. Here we demonstrate by biochemical and immunoelectron microscopic methods that endogenous tetherin is present on the viral particle and forms a bridge between virion particles and the plasma membrane. Endogenous tetherin was found on HIV particles that were released by partial proteolytic digestion. Immunoelectron microscopy performed on HIV-infected T cells demonstrated that tetherin forms an apparent physical link between virions and connects patches of virions to the plasma membrane. Linear filamentous strands that were highly enriched in tetherin bridged the space between some virions. We conclude that tetherin is the physical tether linking HIV-1 virions and the plasma membrane. The presence of filaments with which multiple molecules of tetherin interact in connecting virion particles is strongly suggested by the morphologic evidence

Species-Specific Activity of HIV-1 Vpu and Positive Selection of Tetherin Transmembrane Domain Variants

Tetherin/BST-2/CD317 is a recently identified antiviral protein that blocks the release of nascent retrovirus, and other virus, particles from infected cells. An HIV-1 accessory protein, Vpu, acts as an antagonist of tetherin. Here, we show that positive selection is evident in primate tetherin sequences and that HIV-1 Vpu appears to have specifically adapted to antagonize variants of tetherin found in humans and chimpanzees. Tetherin variants found in rhesus macaques (rh), African green monkeys (agm) and mice were able to inhibit HIV-1 particle release, but were resistant to antagonism by HIV-1 Vpu. Notably, reciprocal exchange of transmembrane domains between human and monkey tetherins conferred sensitivity and resistance to Vpu, identifying this protein domain as a critical determinant of Vpu function. Indeed, differences between hu-tetherin and rh-tetherin at several positions in the transmembrane domain affected sensitivity to antagonism by Vpu. Two alterations in the hu-tetherin transmembrane domain, that correspond to differences found in rh- and agm-tetherin proteins, were sufficient to render hu-tetherin completely resistant to HIV-1 Vpu. Interestingly, transmembrane and cytoplasmic domain sequences in primate tetherins exhibit variation at numerous codons that is likely the result of positive selection, and some of these changes coincide with determinants of HIV-1 Vpu sensitivity. Overall, these data indicate that tetherin could impose a barrier to viral zoonosis as a consequence of positive selection that has been driven by ancient viral antagonists, and that the HIV-1 Vpu protein has specialized to target the transmembrane domains found in human/chimpanzee tetherin proteins

Vaccination coverage and timeliness in three South African areas: a prospective study

<p>Abstract</p> <p>Background</p> <p>Timely vaccination is important to induce adequate protective immunity. We measured vaccination timeliness and vaccination coverage in three geographical areas in South Africa.</p> <p>Methods</p> <p>This study used vaccination information from a community-based cluster-randomized trial promoting exclusive breastfeeding in three South African sites (Paarl in the Western Cape Province, and Umlazi and Rietvlei in KwaZulu-Natal) between 2006 and 2008. Five interview visits were carried out between birth and up to 2 years of age (median follow-up time 18 months), and 1137 children were included in the analysis. We used Kaplan-Meier time-to-event analysis to describe vaccination coverage and timeliness in line with the Expanded Program on Immunization for the first eight vaccines. This included Bacillus Calmette-Guérin (BCG), four oral polio vaccines and 3 doses of the pentavalent vaccine which protects against diphtheria, pertussis, tetanus, hepatitis B and Haemophilus influenzae type B.</p> <p>Results</p> <p>The proportion receiving all these eight recommended vaccines were 94% in Paarl (95% confidence interval [CI] 91-96), 62% in Rietvlei (95%CI 54-68) and 88% in Umlazi (95%CI 84-91). Slightly fewer children received all vaccines within the recommended time periods. The situation was worst for the last pentavalent- and oral polio vaccines. The hazard ratio for incomplete vaccination was 7.2 (95%CI 4.7-11) for Rietvlei compared to Paarl.</p> <p>Conclusions</p> <p>There were large differences between the different South African sites in terms of vaccination coverage and timeliness, with the poorer areas of Rietvlei performing worse than the better-off areas in Paarl. The vaccination coverage was lower for the vaccines given at an older age. There is a need for continued efforts to improve vaccination coverage and timeliness, in particular in rural areas.</p> <p>Trial registration number</p> <p>ClinicalTrials.gov: <a href="http://clinicaltrials.gov/ct2/show/NCT00397150">NCT00397150</a></p

Polarity Changes in the Transmembrane Domain Core of HIV-1 Vpu Inhibits Its Anti-Tetherin Activity

Tetherin (BST-2/CD317) is an interferon-inducible antiviral protein that restricts the release of enveloped viruses from infected cells. The HIV-1 accessory protein Vpu can efficiently antagonize this restriction. In this study, we analyzed mutations of the transmembrane (TM) domain of Vpu, including deletions and substitutions, to delineate amino acids important for HIV-1 viral particle release and in interactions with tetherin. The mutants had similar subcellular localization patterns with that of wild-type Vpu and were functional with respect to CD4 downregulation. We showed that the hydrophobic binding surface for tetherin lies in the core of the Vpu TM domain. Three consecutive hydrophobic isoleucine residues in the middle region of the Vpu TM domain, I15, I16 and I17, were important for stabilizing the tetherin binding interface and determining its sensitivity to tetherin. Changing the polarity of the amino acids at these positions resulted in severe impairment of Vpu-induced tetherin targeting and antagonism. Taken together, these data reveal a model of specific hydrophobic interactions between Vpu and tetherin, which can be potentially targeted in the development of novel anti-HIV-1 drugs