Gargle pool PCR testing in a hospital during medium and high SARS-CoV-2 incidence.

BACKGROUND: Hospitals need to be protected from SARS-CoV-2 infections to protect vulnerable patients. Thus, a safe, efficient, and cost-effective SARS-CoV-2 testing system for hospitals, in addition to standard hygiene measures and vaccination of staff, is necessary. Here we report on the feasibility and performance of a pool real-time reverse-transcriptase polymerase-chain-reaction (rRT-PCR) test system at, medium and high incidence. METHODS: We implemented a testing concept based on gargling at home and pooling of samples in the hospital before PCR testing in the laboratory. We used two PCR systems (point of care and standard 96-well plate system) to adapt to challenges in the hospital setting and respond to a rising incidence in the Omicron wave. FINDINGS: During our 10-week study period, we performed 697 pool PCRs (8793 tests in total) and identified 65 asymptomatic staff members by pool PCR and 94 symptomatic staff members by positive individual PCR. Virus loads in those detected by pool testing were significantly lower (P<0.001). The test system remained workable even during the peak of the Omicron wave and no outbreaks occurred in any specific area of the hospital during the study period. Unvaccinated individuals were over-represented in the positively tested (37% vs 22% positive tests, P=0.04). The test procedure was well accepted by a majority of the hospital staff (84%). CONCLUSION: Repeated gargle pool rRT-PCR testing can be implemented quickly in hospitals and is an effective, easily adaptable and well-accepted test system for hospitals, even during phases with very high infection rates.

Anesthetic management of a parturient with Stiff person syndrome for urgent cesarean delivery.

Stiff person syndrome is a rare neurologic disorder with an estimated incidence of 1:1000000. The underlying pathophysiology is truncal and proximal limb muscle stiffness resulting from continuous co-contracture of agonist and antagonist muscle groups concomitant with superimposed episodic muscle spasms. Loss of gamma-aminobutyric acid-mediated inhibition creates chronic excitation manifested by tonic agonist-antagonist muscle contraction. To date, only three case reports referred indirectly to the anesthetic management of parturients with Stiff person syndrome. The authors describe their management of a parturient with Stiff person syndrome who underwent urgent cesarean delivery under epidural anesthesia.

MiRNome and transcriptome aided pathway analysis in human regulatory T cells.

Owing to their manifold immune regulatory functions, regulatory T cells (Treg) have received tremendous interest as targets for therapeutic intervention of diverse immunological pathologies or cancer. Directed manipulation of Treg will only be achievable with extensive knowledge about the intrinsic programs that define their regulatory function. We simultaneously analyzed miR and mRNA transcript levels in resting and activated human Treg cells in comparison with non-regulatory conventional T cells (Tcon). Based on experimentally validated miR-target information, both transcript levels were integrated into a comprehensive pathway analysis. This strategy revealed characteristic signal transduction pathways involved in Treg biology such as T-cell receptor-, Toll-like receptor-, transforming growth factor-ß-, JAK/STAT (Janus kinase/signal transducers and activators of transcription)- and mammalian target of rapamycin signaling, and allowed for the prediction of specific pathway activities on the basis of miR and mRNA transcript levels in a probabilistic manner. These data encourage new concepts for targeted control of Treg cell effector functions.

H-index is a sensitive indicator of academic activity in highly productive anaesthesiologists: results of a bibliometric analysis.

BACKGROUND: H-index distinguishes differences in scholarly output across faculty ranks in anaesthesiologists, but whether h-index also identifies differences in other aspects of productivity is unknown. We tested the hypothesis that h-index is an indicator of not only publication record, but also grant funding and mentoring in highly productive US academic anaesthesiologists. METHODS: We conducted an internet analysis of the Foundation for Anesthesia Education and Research Academy of Research Mentors in Anesthesiology (n = 43). Publications, citations, citations per publication, and h-index for each investigator were obtained using the Scopus(®) . Total grants, active grants, years of funding, and duration of longest funded grant were recorded using the US National Institutes of Health Research Portfolio Online Reporting Tools(®) . Members were surveyed to identify the number of their career trainees and those who obtained independent funding. RESULTS: The median [IRQ (Interquartile range)] h-index of members was 23 [17-32 (8-50)]. Members published 136 [100-225 (39-461)] papers with 3573 [1832-5090 (150-11,601)] citations and 21 [15-32 (4-59)] citations per publication. Members received four [3-7 (0-10)] grants and were funded for 29 [17-45 (0-115)] grant-years. Survey respondents (79%) mentored 40 [26-69 (15-191)] trainees, three [2-6 (0-20)] of which subsequently received funding. Members with h-indices greater than the median had more publications, citations, citations per publication, grants, and years of funding compared with their counterparts. H-index was associated with total citations, active grants, and the number of trainees. CONCLUSIONS: In addition to publication record, h-index sensitively indicates grant funding and mentoring in highly productive US academic anaesthesiologists.

An analysis of scholarly productivity in United States academic anaesthesiologists by citation bibliometrics.

The h-index is used to evaluate scholarly productivity in academic medicine, but has not been extensively used in anaesthesia. We analysed the publications, citations, citations per publication and h-index from 1996 to date using the Scopus(®) database for 1630 (1120 men, 510 women) for faculty members from 24 randomly selected US academic anaesthesiology departments The median (interquartile range [range]) h-index of US academic anaesthesiologists was 1 [0-5 (0-44)] with 3 [0-18 (0-398)] total publications, 24 [0-187 (0-8515)] total citations, and 5 [0-14 (0-252)] citations per publication. Faculty members in departments with National Institutes of Health funding were more productive than colleagues in departments with little or no government funding. The h-index increased significantly between successive academic ranks concomitant with increases in the number of publications and total citations. Men had higher median h-index than women concomitant with more publications and citations, but the number of citations per publication was similar between groups. Our results suggest that h-index is a reasonable indicator of scholarly productivity in anaesthesia. The results may help comparisons of academic productivity across countries and may be used to assess whether new initiatives designed to reverse recent declines in academic anaesthetic are working. You can respond to this article at http://www.anaesthesiacorrespondence.com.

Bibliometric analysis of anaesthesia journal editorial board members: correlation between journal impact factor and the median h-index of its board members.

BACKGROUND: h-index is useful for quantifying scholarly activity in medicine, but this statistic has not been extensively applied as a measure of productivity in anaesthesia. We conducted a bibliometric analysis of h-index in editorial board members and tested the hypothesis that editorial board members of anaesthesia journals with higher impact factors (IFs) have higher h-indices. METHODS: Ten of 19 journals with 2009 IF>1 were randomly chosen from Journal Citation Reports(®). Board members were identified using each journal's website. Publications, citations, citations per publication, and h-index for each member were obtained using Scopus(®). RESULTS: Four hundred and twenty-three individuals filled 481 anaesthesia editorial board positions. The median h-index of all editorial board members was 14. Board members published 75 papers (median) with 1006 citations and 13 citations per publication. Members serving on journals with IF greater than median had significantly (P<0.05; Wilcoxon's rank-sum test) greater median h-index, citations, and citations per publication than those at journals with IF less than median. A significant correlation between the median h-index of a journal's editorial board members and its IF (h-index=3.01×IF+6.85; r( 2)=0.452; P=0.033) was observed for the 10 journals examined. Board members of subspeciality-specific journals had bibliometric indices that were less than those at general journals. The h-index was greater in individuals serving more than one journal. European editorial board members had higher h-index values than their American colleagues. CONCLUSIONS: The results suggest that editorial board members of anaesthesia journals with higher IFs have higher h-indices.

Ketamine attenuates post-operative cognitive dysfunction after cardiac surgery.

BACKGROUND: Post-operative cognitive dysfunction (POCD) commonly occurs after cardiac surgery. Ketamine exerts neuroprotective effects after cerebral ischemia by anti-excitotoxic and anti-inflammatory mechanisms. We hypothesized that ketamine attenuates POCD in patients undergoing cardiac surgery concomitant with an anti-inflammatory effect. METHODS: Patients randomly received placebo (0.9% saline; n=26) or an i.v. bolus of ketamine (0.5 mg/kg; n=26) during anesthetic induction. Anesthesia was maintained with isoflurane and fentanyl. A nonsurgical group (n=26) was also included as control. Recent verbal and nonverbal memory and executive functions were assessed before and 1 week after surgery or a 1-week waiting period for the nonsurgical controls. Serum C-reactive protein (CRP) concentrations were determined before surgery and on the first post-operative day. RESULTS: Baseline neurocognitive and depression scores were similar in the placebo, ketamine, and nonsurgical control groups. Cognitive performance after surgery decreased by at least 2 SDs (z-score of 1.96) in 21 patients in the placebo group and only in seven patients in the ketamine group compared with the nonsurgical controls (P<0.001, Fisher's exact test). Cognitive performance was also significantly different between the placebo- and the ketamine-treated groups based on all z-scores (P<0.001, Mann-Whitney U-test). Pre-operative CRP concentrations were similar (P<0.33, Mann-Whitney U-test) in the placebo- and ketamine-treated groups. The post-operative CRP concentration was significantly (P<0.01, Mann-Whitney U-test) lower in the ketamine-treated than in the placebo-treated group. CONCLUSIONS: Ketamine attenuates POCD 1 week after cardiac surgery and this effect may be related to the anti-inflammatory action of the drug.

Suxamethonium-induced hyperkalaemia 6 weeks after chemoradiotherapy in a patient with rectal carcinoma.

Suxamethonium causes an efflux of potassium (K+) ions by depolarizing acetylcholine receptors within the neuromuscular junction and produces a transient, small rise in serum K+ concentration in normal individuals that is usually of little clinical importance. Despite the clear efficacy and relative safety of suxamethonium in many patients, anaesthetists are also very aware that acute, severe hyperkalaemia resulting in important cardiovascular sequelae (e.g. malignant ventricular arrhythmias, cardiac arrest) may also occur with administration of suxamethonium in susceptible patients, including those with skeletal muscle injury or thermal trauma. In the current report, we describe a patient with rectal cancer initially treated with chemoradiotherapy who developed hyperkalaemia after suxamethonium and further discuss the potential factors that contributed to this response.

MIPS: analysis and annotation of proteins from whole genomes in 2005.

The Munich Information Center for Protein Sequences (MIPS at the GSF), Neuherberg, Germany, provides resources related to genome information. Manually curated databases for several reference organisms are maintained. Several of these databases are described elsewhere in this and other recent NAR database issues. In a complementary effort, a comprehensive set of >400 genomes automatically annotated with the PEDANT system are maintained. The main goal of our current work on creating and maintaining genome databases is to extend gene centered information to information on interactions within a generic comprehensive framework. We have concentrated our efforts along three lines (i) the development of suitable comprehensive data structures and database technology, communication and query tools to include a wide range of different types of information enabling the representation of complex information such as functional modules or networks Genome Research Environment System, (ii) the development of databases covering computable information such as the basic evolutionary relations among all genes, namely SIMAP, the sequence similarity matrix and the CABiNet network analysis framework and (iii) the compilation and manual annotation of information related to interactions such as protein-protein interactions or other types of relations (e.g. MPCDB, MPPI, CYGD). All databases described and the detailed descriptions of our projects can be accessed through the MIPS WWW server (http://mips.gsf.de).

MIPS: analysis and annotation of proteins from whole genomes.

The Munich Information Center for Protein Sequences (MIPS-GSF), Neuherberg, Germany, provides protein sequence-related information based on whole-genome analysis. The main focus of the work is directed toward the systematic organization of sequence-related attributes as gathered by a variety of algorithms, primary information from experimental data together with information compiled from the scientific literature. MIPS maintains automatically generated and manually annotated genome-specific databases, develops systematic classification schemes for the functional annotation of protein sequences and provides tools for the comprehensive analysis of protein sequences. This report updates the information on the yeast genome (CYGD), the Neurospora crassa genome (MNCDB), the database of complete cDNAs (German Human Genome Project, NGFN), the database of mammalian protein-protein interactions (MPPI), the database of FASTA homologies (SIMAP), and the interface for the fast retrieval of protein-associated information (QUIPOS). The Arabidopsis thaliana database, the rice database, the plant EST databases (MATDB, MOsDB, SPUTNIK), as well as the databases for the comprehensive set of genomes (PEDANT genomes) are described elsewhere in the 2003 and 2004 NAR database issues, respectively. All databases described, and the detailed descriptions of our projects can be accessed through the MIPS web server (http://mips.gsf.de).

Hyperglycemia reduces coronary collateral blood flow through a nitric oxide-mediated mechanism.

We tested the hypothesis that hyperglycemia alters retrograde coronary collateral blood flow by a nitric oxide-mediated mechanism in a canine Ameriod constrictor model of enhanced collateral development. Administration of 15% dextrose to increase blood glucose concentration to 400 or 600 mg/dl decreased retrograde blood flow through the left anterior descending coronary artery to 78 +/- 9 and 82 +/- 8% of baseline values, respectively. In contrast, saline or L-arginine (400 mg x kg(-1) x h(-1)) had no effect on retrograde flow. Coronary hypoperfusion and 1 h of reperfusion decreased retrograde blood flow similarly in saline- or L-arginine-treated dogs (76 +/- 11 and 89 +/- 4% of baseline, respectively), but these decreases were more pronounced in hyperglycemic dogs (47 +/- 10%). L-arginine prevented decreases in retrograde coronary collateral blood flow during hyperglycemia (100 +/- 5 and 95 +/- 6% of baseline at blood glucose concentrations of 400 and 600 mg/dl, respectively) and after coronary hypoperfusion and reperfusion (84 +/- 14%). The results suggest that hyperglycemia decreases retrograde coronary collateral blood flow by adversely affecting nitric oxide availability.

Desflurane, sevoflurane, and isoflurane affect left atrial active and passive mechanical properties and impair left atrial-left ventricular coupling in vivo: analysis using pressure-volume relations.

BACKGROUND: The effects of volatile anesthetics on left atrial function in vivo have not been described. The authors tested the hypothesis that desflurane, sevoflurane, and isoflurane alter left atrial mechanics evaluated with invasively derived pressure-volume relations. METHODS: Barbiturate-anesthetized dogs (n = 24) were instrumented for measurement of aortic, left atrial, and left ventricular pressures (micromanometers) and left atrial volume (orthogonal sonomicrometers). Left atrial contractility and chamber stiffness were assessed with end-systolic and end-reservoir pressure-volume relations, respectively, obtained from differentially loaded diagrams. Relaxation was determined from the slope of left atrial pressure decline after contraction. Stroke work and reservoir function were assessed by A and V loop areas, respectively. Left atrial-left ventricular coupling was determined by the ratio of left atrial contractility and left ventricular elastance. Dogs received 0.6, 0.9, and 1.2 minimum alveolar concentration desflurane, sevoflurane, or isoflurane in a random manner, and left atrial function was determined after 20-min equilibration at each dose. RESULTS: Desflurane, sevoflurane, and isoflurane decreased heart rate, mean arterial pressure, and maximal rate of increase of left ventricular pressure and increased left atrial end-diastolic, end-systolic, and maximum volumes. All three anesthetics caused dose-related reductions in left atrial contractility, relaxation, chamber stiffness, and stroke work. Administration of 0.6 and 0.9 minimum alveolar concentration desflurane, sevoflurane, and isoflurane increased V loop area. All three anesthetics decreased the ratio of stroke work to total left atrial pressure-volume diagram area, increased the ratio of conduit to reservoir volume, and reduced left atrial contractility-left ventricular elastance to equivalent degrees. CONCLUSIONS: The results indicate that desflurane, sevoflurane, and isoflurane depress left atrial contractility, delay relaxation, reduce chamber stiffness, preserve reservoir and conduit function, and impair left atrial-left ventricular coupling in vivo.

Conscious sedation with midazolam or propofol does not alter left ventricular diastolic performance in patients with preexisting diastolic dysfunction: a transmitral and tissue Doppler transthoracic echocardiography study.

UNLABELLED: The effects of midazolam and propofol on left ventricular (LV) diastolic function have not been evaluated in humans. We tested the hypothesis that midazolam and propofol alter LV diastolic function evaluated with transmitral and tissue Doppler transthoracic echocardiography in patients with normal LV systolic function in the presence and absence of preexisting diastolic dysfunction. After IRB approval and informed consent, patients (n = 34) with normal or reversed transmitral blood flow velocity E-to-A ratios received 3 escalating doses of midazolam (0.025, 0.05, and 0.1 mg/kg) or propofol (0.25, 0.5, and 1.0 mg/kg) over 10 s at 5-min intervals. Hemodynamic variables and indices of diastolic function were recorded 3 min after each dose of midazolam and propofol. Patients with diastolic dysfunction demonstrated decreased ratios of peak transmitral E-to-A wave velocity and their corresponding time-velocity integrals as compared with normal patients. Reductions in anterior and posterior mitral annulus E/A ratios were also present. Midazolam and propofol did not further alter indices of LV diastolic function in patients with impaired early LV filling. The results indicate that sedation with midazolam or propofol does not affect indices of LV diastolic performance in healthy patients and those with preexisting diastolic dysfunction. IMPLICATIONS: Sedation with midazolam or propofol does not alter indices of left ventricular diastolic function in healthy patients and those with preexisting left ventricular filling abnormalities as evaluated by transthoracic echocardiography.

Diabetes and hyperglycemia impair activation of mitochondrial K(ATP) channels.

Hyperglycemia is an important predictor of cardiovascular mortality in patients with diabetes. We investigated the hypothesis that diabetes or acute hyperglycemia attenuates the reduction of myocardial infarct size produced by activation of mitochondrial ATP-regulated potassium (K(ATP)) channels. Acutely instrumented barbiturate-anesthetized dogs were subjected to a 60-min period of coronary artery occlusion and 3 h of reperfusion. Myocardial infarct size (triphenyltetrazolium chloride staining) was 25 +/- 1, 28 +/- 3, and 25 +/- 1% of the area at risk (AAR) for infarction in control, diabetic (3 wk after streptozotocin-alloxan), and hyperglycemic (15% intravenous dextrose) dogs, respectively. Diazoxide (2.5 mg/kg iv) significantly decreased infarct size (10 +/- 1% of AAR, P < 0.05) but did not produce protection in the presence of diabetes (28 +/- 5%) or moderate hyperglycemia (blood glucose 310 +/- 10 mg/dl; 23 +/- 2%). The dose of diazoxide and the degree of hyperglycemia were interactive. Profound (blood glucose 574 +/- 23 mg/dl) but not moderate hyperglycemia blocked the effects of high-dose (5.0 mg/kg) diazoxide [26 +/- 3, 15 +/- 3 (P < 0.05), and 11 +/- 2% (P < 0.05), respectively]. There were no differences in systemic hemodynamics, AAR, or coronary collateral blood flow (by radioactive microspheres) between groups. The results indicate that diabetes or hyperglycemia impairs activation of mitochondrial K(ATP) channels.

Ethanol enhances the functional recovery of stunned myocardium independent of K(ATP) channels in dogs.

Chronic, intermittent exposure to small amounts of ethanol reduces myocardial infarct size in vivo. We tested the hypothesis that acute administration of ethanol enhances the functional recovery of stunned myocardium and that adenosine triphosphate-dependent potassium (K(ATP)) channels mediate this beneficial effect. Barbiturate-anesthetized dogs were instrumented for measurement of aortic and left ventricular pressure, +dP/dt(max), and subendocardial segment shortening (%SS) and were subjected to five 5-min periods of coronary artery occlusion, each separated by 5 min of reperfusion followed by a 3-h final reperfusion. In four groups (n = 7 each), dogs received 0.9% saline or ethanol (0.25, 0.5, or 1.0 g/kg over 30 min) in a random manner before occlusions and reperfusions. In other groups (n = 7 each), dogs received the K(ATP) channel antagonist glyburide (0.3 mg/kg, IV) 30 min before saline or ethanol (0.25 g/kg) was administered. Dogs receiving saline or glyburide alone demonstrated poor recovery of contractile function during reperfusion (%SS = 0.9% +/- 2.0% and 1.6% +/- 1.2% at 3 h, respectively). Recovery of %SS was enhanced in dogs receiving the 0.25- and 0.5-g/kg doses of ethanol (10.0% +/- 1.8% and 8.6% +/- 2.2% at 3 h, respectively) independent of alterations in hemodynamics or coronary collateral blood flow (radioactive microspheres). Glyburide did not affect improvement of recovery of stunned myocardium produced by ethanol (11.8% +/- 2.2% at 3 h). The results indicate that ethanol enhances the functional recovery of stunned myocardium independent of K(ATP) channels in vivo.

Aldosterone and nuclear volume cycling.

The response of target cells to the steroid hormone aldosterone has been divided into acute nongenomic (< 10 min) and sustained genomic (> 10 min) action. In the light of recent experiments this nomenclature does not hold anymore and should be abandoned. By applying atomic force microscopy (AFM) we observed in living endothelial cells that aldosterone induces cell volume increase in less than 10 minutes. The cell nucleus was identified as the swelling site. Hormone-induced nuclear swelling can reach 15 to 28% of total cell volume dissipating within 30 minutes. This phenomenon could have functional impact on flow resistance in small blood vessels. AFM-investigation of the intracellular signal pathway in nuclear envelope of aldosterone-injected Xenopus laevis oocytes visualizes putative intracellular receptors (40 kD granules) bound to nuclear pores 2 minutes after hormone injection, with subsequent macromolecule translocation into the nucleus. 15 minutes later macromolecules (800 kD plugs) appear in the central channels of the nuclear pores. The plugs resemble ribonucleoproteins that carry the aldosterone-induced mRNA to the ribosomes. We postulate that steroid-induced nuclear swelling is caused by a shift of receptors/transcription factors from cytoplasm into nucleoplasm followed by gene transcription. Nuclear volume returns to normal when mRNA export through the nuclear pores is finished. Thus, steroid-induced net-movements of macromolecules between intracellular compartments initiate shifts in cell volume compensated by volume regulatory transporters and ion channels in the plasma membrane.

Development of a method for sample preparation for subsequent identification and measurement of 1,2,3,4-tetrahydroisoquinolines and other potentially neurotoxic compounds by high-performance liquid chromatography with ultraviolet and fluorescence detection in blood plasma of Parkinson's disease patients.

We developed sample preparation methods for the detection of various biogenic phenylethylamine derivatives such as 3,4-dihydroxyphenylalanine, and their cyclisation products with aldehydes, i.e., 1,2,3,4-tetrahydroisoquinoline derivatives in blood samples. 1,2,3,4-Tetrahydroisoquinolines are considered to play an essential role as neurotoxic compounds in the pathomechanism of Parkinson's disease. We used reversed-phase high-performance liquid chromatography with ultraviolet and fluorescence detection for separation and identification. Ultrafiltration, protein precipitation and solid-phase extraction were investigated for purification of blood samples and enrichment of various compounds with a wide range of hydrophilicity and hydrophobicity. Protein precipitation by methanol and perchloric acid is a fast method to separate the analytes from the plasma matrix. A higher yield of the analytes is attained with prior addition of an alkylsulfonic acid giving a fine-grained precipitate. With the addition of ion pairing compounds into the sample it is possible to enrich not only lipophilic compounds such as norharman, tryptamine and melatonin, but also hydrophilic ones such as 3,4-dihydroxyphenylalanine by reversed-phase solid-phase extraction. Ultrafiltration is not useful as a screening method.

High-performance liquid chromatographic separation and measurement of various biogenic compounds possibly involved in the pathomechanism of Parkinson's disease.

The work presented here describes an optimised, reversed-phase high-performance liquid chromatographic (RP-HPLC) method for separating 46 biogenic compounds, which, as neurotoxins or as their precursors or derivatives, may be relevant in the pathomechanism of Parkinson's disease. In some cases, the physico-chemical properties of these substances are very similar, in other cases they differ greatly. In order to facilitate their detection in one chromatographic run, ion-pair chromatography was uniquely combined with a gradient elution. A diode array or a dual wavelength detector was used in combination with a fluorescence detector to verify the identity of the compounds.