Maternal smoking during pregnancy increases the risk of gut microbiome-associated childhood overweight and obesity.

Childhood obesity is linked to maternal smoking during pregnancy. Gut microbiota may partially mediate this association and could be potential targets for intervention; however, its role is understudied. We included 1,592 infants from the Canadian Healthy Infants Longitudinal Development Cohort. Data on environmental exposure and lifestyle factors were collected prenatally and throughout the first three years. Weight outcomes were measured at one and three years of age. Stool samples collected at 3 and 12 months were analyzed by sequencing the V4 region of 16S rRNA to profile microbial compositions and magnetic resonance spectroscopy to quantify the metabolites. We showed that quitting smoking during pregnancy did not lower the risk of offspring being overweight. However, exclusive breastfeeding until the third month of age may alleviate these risks. We also reported that maternal smoking during pregnancy significantly increased Firmicutes abundance and diversity. We further revealed that Firmicutes diversity mediates the elevated risk of childhood overweight and obesity linked to maternal prenatal smoking. This effect possibly occurs through excessive microbial butyrate production. These findings add to the evidence that women should quit smoking before their pregnancies to prevent microbiome-mediated childhood overweight and obesity risk, and indicate the potential obesogenic role of excessive butyrate production in early life.

A synbiotic preparation (SIM01) for post-acute COVID-19 syndrome in Hong Kong (RECOVERY): a randomised, double-blind, placebo-controlled trial.

BACKGROUND: Post-acute COVID-19 syndrome (PACS) affects over 65 million individuals worldwide but treatment options are scarce. We aimed to assess a synbiotic preparation (SIM01) for the alleviation of PACS symptoms. METHODS: In this randomised, double-blind, placebo-controlled trial at a tertiary referral centre in Hong Kong, patients with PACS according to the US Centers for Disease Control and Prevention criteria were randomly assigned (1:1) by random permuted blocks to receive SIM01 (10 billion colony-forming units in sachets twice daily) or placebo orally for 6 months. Inclusion criterion was the presence of at least one of 14 PACS symptoms for 4 weeks or more after confirmed SARS-CoV-2 infection, including fatigue, memory loss, difficulty in concentration, insomnia, mood disturbance, hair loss, shortness of breath, coughing, inability to exercise, chest pain, muscle pain, joint pain, gastrointestinal upset, or general unwellness. Individuals were excluded if they were immunocompromised, were pregnant or breastfeeding, were unable to receive oral fluids, or if they had received gastrointestinal surgery in the 30 days before randomisation. Participants, care providers, and investigators were masked to group assignment. The primary outcome was alleviation of PACS symptoms by 6 months, assessed by an interviewer-administered 14-item questionnaire in the intention-to-treat population. Forward stepwise multivariable logistical regression was performed to identify predictors of symptom alleviation. The trial is registered with ClinicalTrials.gov, NCT04950803. FINDINGS: Between June 25, 2021, and Aug 12, 2022, 463 patients were randomly assigned to receive SIM01 (n=232) or placebo (n=231). At 6 months, significantly higher proportions of the SIM01 group had alleviation of fatigue (OR 2·273, 95% CI 1·520-3·397, p=0·0001), memory loss (1·967, 1·271-3·044, p=0·0024), difficulty in concentration (2·644, 1·687-4·143, p<0·0001), gastrointestinal upset (1·995, 1·304-3·051, p=0·0014), and general unwellness (2·360, 1·428-3·900, p=0·0008) compared with the placebo group. Adverse event rates were similar between groups during treatment (SIM01 22 [10%] of 232 vs placebo 25 [11%] of 231; p=0·63). Treatment with SIM01, infection with omicron variants, vaccination before COVID-19, and mild acute COVID-19, were predictors of symptom alleviation (p<0·0036). INTERPRETATION: Treatment with SIM01 alleviates multiple symptoms of PACS. Our findings have implications on the management of PACS through gut microbiome modulation. Further studies are warranted to explore the beneficial effects of SIM01 in other chronic or post-infection conditions. FUNDING: Health and Medical Research Fund of Hong Kong, Hui Hoy and Chow Sin Lan Charity Fund, and InnoHK of the HKSAR Government. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Intravenous Lidocaine for Treatment of Chronic Pain: A Retrospective Cohort Study.

Introduction: Neuropathic pain is a widespread problem with a big impact on quality of life. The currently used drug regimens are often insufficiently effective or cause - sometimes unacceptable - side effects. Intravenous lidocaine could be an alternative treatment, by blocking spontaneous depolarization and hyperexcitability in upregulated sodium channels in nociceptors. Research so far has shown varying results but the treatment protocols differed a lot and follow-up was usually short. In our hospital, lidocaine infusions have been applied for many years in a unique treatment protocol consisting of a relatively high dose of lidocaine (1000 mg) administered over 25 hours. Our aim is to share information on both the efficacy and safety of this treatment schedule. Methods: We conducted a retrospective cohort study in all patients who received a lidocaine infusion between January 2014 and January 2018. The standard infusion protocol consists of a total of 1000 mg lidocaine administered intravenously during 25 hours (40 mg/hour). Pain diagnoses were stratified into 15 groups, in agreement with diagnoses used in daily practice. Effectiveness of the treatment was classified as effect or no effect based on the description found in the chart. Results: We included 282 patients, with a median age of 58 years and 64% of whom were female. Patients with myofascial pain syndrome, peripheral (mono)neuropathy, small fiber neuropathy and vascular disease benefited most. Patients with cancer pain, postherpetic neuralgia, chemotherapy-induced neuropathy and radicular pain showed the least pain improvement. There were no serious adverse events. Conclusion: In selected patients, lidocaine infusions may be a safe and efficacious treatment for chronic neuropathic pain. More prospective research is needed to further determine the optimal dosing, duration and interval of lidocaine infusion therapy, and to better understand in which specific patient categories this treatment is most beneficial.

Faecal microbiome-based machine learning for multi-class disease diagnosis.

Systemic characterisation of the human faecal microbiome provides the opportunity to develop non-invasive approaches in the diagnosis of a major human disease. However, shared microbial signatures across different diseases make accurate diagnosis challenging in single-disease models. Herein, we present a machine-learning multi-class model using faecal metagenomic dataset of 2,320 individuals with nine well-characterised phenotypes, including colorectal cancer, colorectal adenomas, Crohn's disease, ulcerative colitis, irritable bowel syndrome, obesity, cardiovascular disease, post-acute COVID-19 syndrome and healthy individuals. Our processed data covers 325 microbial species derived from 14.3 terabytes of sequence. The trained model achieves an area under the receiver operating characteristic curve (AUROC) of 0.90 to 0.99 (Interquartile range, IQR, 0.91-0.94) in predicting different diseases in the independent test set, with a sensitivity of 0.81 to 0.95 (IQR, 0.87-0.93) at a specificity of 0.76 to 0.98 (IQR 0.83-0.95). Metagenomic analysis from public datasets of 1,597 samples across different populations observes comparable predictions with AUROC of 0.69 to 0.91 (IQR 0.79-0.87). Correlation of the top 50 microbial species with disease phenotypes identifies 363 significant associations (FDR < 0.05). This microbiome-based multi-disease model has potential clinical application in disease diagnostics and treatment response monitoring and warrants further exploration.

Pyrosequencing of the bacteria associated with Platygyra carnosus corals with skeletal growth anomalies reveals differences in bacterial community composition in apparently healthy and diseased tissues.

Corals are rapidly declining globally due to coral diseases. Skeletal growth anomalies (SGA) or "coral tumors" are a group of coral diseases that affect coral reefs worldwide, including Hong Kong waters in the Indo-Pacific region. To better understand how bacterial communities may vary in corals with SGA, for the first time, we examined the bacterial composition associated with the apparently healthy and the diseased tissues of SGA-affected Platgyra carnosus using 16S ribosomal rRNA gene pyrosequencing. Taxonomic analysis revealed Proteobacteria, Bacteroidetes, Cyanobacteria, and Actinobacteria as the main phyla in both the apparently healthy and the diseased tissues. A significant difference in the bacterial community composition was observed between the two conditions at the OTU level. Diseased tissues were associated with higher abundances of Acidobacteria and Gemmatimonadetes, and a lower abundance of Spirochaetes. Several OTUs belonging to Rhodobacteraceae, Rhizobiales, Gammaproteobacteria, and Cytophaga-Flavobacterium-Bacteroidetes (CFB) were strongly associated with the diseased tissues. These groups of bacteria may contain potential pathogens involved with the development of SGA or opportunistic secondary or tertiary colonizers that proliferated upon the health-compromised coral host. We suggest that these bacterial groups to be further studied based on inoculation experiments and testing of Koch's postulates in efforts to understand the etiology and progression of SGA.

Acute effects of superimposed electromyostimulation during cycling on myokines and markers of muscle damage.

OBJECTIVES: The purpose of the present study was to evaluate the effects of superimposed electromyostimulation (E) during cycling on myokines and markers of muscle damage, as E might be a useful tool to induce a high local stimulus to skeletal muscle during endurance training without performing high external workloads. METHODS: 13 subjects participated in three experimental trials each lasting 60 min in a randomized order. 1) Cycling (C), 2) Cycling with superimposed E (C+E) and 3) E. Interleukin-6 (IL-6), brain-derived neurotrophic factor (BDNF), creatine kinase (CK) and myoglobin were determined before (pre) and 0', 30', 60', 240' and 24h after each intervention. RESULTS: Only C+E caused significant increases in levels of CK and myoglobin. BDNF and IL-6 significantly increased after C and C+E, however increases for IL-6 were significantly higher after C+E compared to C. CONCLUSION: The present study showed that superimposed E during cycling might be a useful tool to induce a high local stimulus to skeletal muscle even when performing low to moderate external workloads. This effect might be due the activation of additional muscle fibers and mild eccentric work due to the concomitant activation of agonist and antagonist. However the higher load to skeletal muscle has to be taken into account.

Simplified detection of myocardial ischemia by seismocardiography. Differentiation between causes of altered myocardial function.

Seismocardiography (SCG) is a noninvasive technique for recording cardiac vibrations. Changes in these waves have been correlated with chronic and acute alterations in myocardial function. This analysis is complex and clinical integration limited. The current study aimed to simplify the utilization of SCG by fast Fourier transformation for a reliable discrimination between different intra- and postoperative causes of hypotension (i.e., myocardial ischemia or hypovolemia). We operated on nine pigs and recorded SCG at baseline, at hypovolemia (occlusion of the inferior vena cava), and at ischemia (occlusion of the right coronary artery). In conclusion, SCG enables detection and differentiation of ischemia and hypovolemia as important causes of altered myocardial function during and after surgery. Thus, this simple and noninvasive diagnostic tool may be used intra- and postoperatively to identify patients at risk.

Myocardial effects of local shock wave therapy in a Langendorff model.

OBJECTIVE: Applying shock waves to the heart has been reported to stimulate the heart and alter cardiac function. We hypothesized that shock waves could be used to diagnose regional viability. METHOD: We used a Langendorff model to investigate the acute effects of shock waves at different energy levels and times related to systole, cycle duration and myocardial function. RESULTS: We found only a small time window to use shock waves. Myocardial fibrillation or extrasystolic beats will occur if the shock wave is placed more than 15 ms before or 30 ms after the onset of systole. Increased contractility and augmented relaxation were observed after the second beat, and these effects decreased after prolonging the shock wave delay from 15 ms before to 30 ms after the onset of systole. An energy dependency could be found only after short delays (-15 ms). The involved processes might include post-extrasystolic potentiation and simultaneous pacing. CONCLUSION: In summary, we found that low-energy shock waves can be a useful tool to stimulate the myocardium at a distance and influence function.

Xenon is not superior to isoflurane on cardiovascular function during experimental acute pulmonary hypertension.

BACKGROUND: Acute right ventricular afterload increase is a known perioperative challenge for the anaesthetic regime especially for patients with a compromised right ventricle. The accused negative inotropic action of volatile anaesthetics, with the exception of xenon, might be crucial for the adaptation of the right ventricle. METHODS: Reversible pulmonary hypertension (mean pressure 40 mmHg) was induced by an infusion of the stable thromboxane A(2) analog U46619 in a porcine model (n = 35). The effects of 70 vol% xenon and 0.9 vol% isoflurane on biventricular function were studied by conductance catheter technique. Inflammation and myocardial injury was quantified using serum probes [tumour necrosis factor α (TNFα), interleukin 6 (IL-6), troponin] and myocardial tissue [B natriuretic peptide (BNP), TNFα, activated caspase 3] by enzyme-linked immunosorbance assays and reverse-transcription polymerase chain reaction. RESULTS: After wash in of xenon global haemodynamic parameters remained stable whereas isoflurane caused a systemic vasodilation. This led to a significant decrease in mean arterial pressure in the isoflurane group whereas cardiac output remained stable. Both substances did not alter the biventricular contractility nor did they induce changes in preload for both ventricles. Xenon led to an additional increase in right ventricular afterload, whereas isoflurane reduced pulmonary vascular resistance. No effects on systemic inflammatory response and myocardial injury were found, whereas higher apoptosis rate and expression of BNP and IL-6 was determined in the right ventricle. CONCLUSIONS: These results do not support the idea that xenon is more beneficial than isoflurane in right ventricular failure during pulmonary hypertension. Isoflurane did not compromise systolic ventricular function during acute PHT it only led to vasodilation in contrast to xenon.

The effects of metoprolol on hypoxia- and isoflurane-induced cardiac late-phase preconditioning.

BACKGROUND: The detrimental effects of metoprolol on early-phase preconditioning (pc) have been proven. The late phase of pc is mediated via gene transcription and cyclooxygenase-2 (COX-2) was identified as one of the key mediators. The effect of metoprolol on this is yet unknown as is its effect on cellular energy metabolism and reactive oxygen species (ROS) creation. METHODS: Cardiomyocytes from neonatal rats were cultured and randomly assigned to four pairs of treatment groups. In each pair, one group received metoprolol at a dose of 0.5 µg/ml medium. One pair served as a control; the others were subjected to 5 h of hypoxia 24 h after either hypoxia-induced, isoflurane-induced or no pc. Cell survival was measured with a redox indicator for cell metabolism. COX-2 transcription, ATP and ROS creation were measured. RESULTS: Whereas both ischemic and isoflurane pc produced mild beneficial effects (48.8±6.0% and 48.2±7.8% of surviving cells, respectively) compared with unpreconditioned controls (35.9±7.9%, P<0.01 for both), adding metoprolol was detrimental for both kinds of pc (hypoxia: 31.5±3.5%; isoflurane: 25.7±3.8%, P<0.001) but not in the unpreconditioned group (39.4±4.9%). mRNA for COX-2 was up to 10-fold elevated in pc cells. This induction was suppressed by metoprolol. Hypoxic and isoflurane-induced pc showed significant differences in ATP balance and ROS generation. CONCLUSION: Metoprolol abolishes the protection of both isoflurane- and hypoxia-induced late-phase pc in our model. This effect is accompanied by the blockade of COX-2 induction. The differences between hypoxic and isoflurane pc in ATP and ROS creation allow to presume distinct pathways on the mitochondrial level.

Comprehensive array CGH of normal karyotype myelodysplastic syndromes reveals hidden recurrent and individual genomic copy number alterations with prognostic relevance.

About 40% of patients with myelodysplastic syndromes (MDSs) present with a normal karyotype, and they are facing different courses of disease. To advance the biological understanding and to find molecular prognostic markers, we performed a high-resolution oligonucleotide array study of 107 MDS patients (French American British) with a normal karyotype and clinical follow-up through the Duesseldorf MDS registry. Recurrent hidden deletions overlapping with known cytogenetic aberrations or sites of known tumor-associated genes were identified in 4q24 (TET2, 2x), 5q31.2 (2x), 7q22.1 (3x) and 21q22.12 (RUNX1, 2x). One patient with a 7q22.1 deletion had an additional 5q31.2 deletion of the acute myeloid leukemia/MDS region, the smallest deletion identified so far and including the putative tumor suppressor (ts) genes, EGR1 and CTNNA1. One TET2 deletion was homozygous and one heterozygous, with a missense mutation in the remaining allele, further supporting its role as a ts gene. Besides these recurrent alterations, additional individual imbalances were found in 34 cases; in total, 42/107 (39%) cases had genomic imbalances. These patients had an inferior survival as compared with the rest of the patients (P=0.002). This study emphasizes the heterogeneity of MDS, but points to interesting genes that may have diagnostic and prognostic impact.

Accidental renal injury by an external heating device during surgery in rats.

Hypothermia can be caused by anaesthesia and/or surgery and represents a daily challenge in the operating room. Experimental animal surgery settings typically use heating pads or warming blankets to maintain the rodent's body temperature during long-lasting experiments. Warming is crucial in small animal experiments because these animals quickly lose temperature due to their large body surface to body weight ratio. While establishing a left ventricular infarction model in rats, we inserted a rectal temperature probe. The heating pad's set point was 37°C. Although a dual set point control circuit should prevent overheating, we observed a maximum heating pad's surface temperature of 43°C between the animal's back and the surface of the heating pad. At the end of the experiments, which lasted up to 8 h, the animals showed severe haematuria and segmental kidney damage. We hypothesized that overheating of the heating pad and uneven distribution of temperature led to kidney damage. Therefore, the maximal temperature of commonly used heating pads must be tightly controlled to avoid overheating, which may cause kidney or tissue injury, may falsify the experimental data and could influence the study results.

Evaluación de la toxicidad subaguda del Camu-camu (Myrciaria dubia) administrado por vía oral en ratas / n vitro evaluation of the subacute toxicity of oral administration of (Myrciaria dubia) Camu-camu in rats / I

Camu-camu, es un árbol frutal, oriundo de la amazonía sudamericana que crece en las orillas anegables de ríos amazónicos. Pertenece al género Myrciaria, especie dubia. Presenta gran importancia nutritiva. Su alto contenido en ácido ascórbico (2780 mg/100 g de pulpa) le confieren propiedades antioxidantes. Objetivo: Evaluar la toxicidad subaguda (30 días) del Camu-camu. Material y método: Utilizamos 33 ratas albinas, macho, Holtzman, distribuidas en 3 grupos equitativos: Grupo I (grupo control), se le administró agua destilada, Grupo II y Grupo III, se les administró por vía oral el extracto seco de Camu-camu a las dosis de 100 y 200mg/Kg, respectivamente. Al inicio del experimento (basal), a las 15 y a los 30 días, se determinó: hemoglobina, WBC, urea, albúmina, creatinina, proteínas GGT, TGP, TGO, en sangre, y peso corporal; además, se realizó el examen histológico de hígado, riñones, bazo y estómago al finalizar el estudio (30 días). Resultados: Los valores de hemoglobina, albúmina y proteínas, fueron mayores que las del grupo control (p<0.05); a su vez, los valores de GGT fueron menores que los del grupo control (p<0.05). No encontramos evidencias de toxicidad sub-aguda, en ninguno de los 2 grupos expuestos, en el examen histopatológico. Conclusión: El Camu-camu, a las dosis y formas de administración, del presente trabajo, carece de efectos tóxicos para las ratas.

Camu-camu, is a native fruit tree of the South American jungle and grows at the borders of amazonian rivers. It belongs to Myrciaria generous and dubia specie and has a great nutritional importance. Contains a high amounts of ascorbic acid, (2780mg/100g of pulp), that is why it is good antioxidant. Objective: To evaluate the subacute toxicity of the atomized Camu-camu. Material and method: We used 33 Holtzman albino male rats, distributed in 3 equitable groups: Group I, the control group, only received distilled water, Groups II and III received 100 and 200 mg/Kg of Camu-camu, respectively. Blood samples were taken for biochemical analysis at the beginning, 15th and 30th days (at the end), to determinate Hb, WBC, urea, albumin, total proteins, creatinine, GGT, TGP, TGO and the weight of the animals; we also do the histological examination of liver, kidneys, spleen and stomach at the end of the experiments (day 30th). Results: The values of albumin, total proteins and hemoglobin were higher than the control group (p<0.05) while the values of GGT were lower that control group (p<0.05). We didnÆt find evidences of subacute toxicity in any of the 2 groups exposed to Camu-camu in the histopathological examination. Conclusion: Camu camu hadn´t toxic effect, in rats, with oral administration during 30 days.

Anti-ischemic effects of inotropic agents in experimental right ventricular infarction.

BACKGROUND: Right ventricular (RV) function is an important determinant of survival after myocardial infarction. The efficacy of reperfusion therapy might be increased by the cardioprotective action of inotropic agents, which are used for symptomatic therapy in situations with compromised hemodynamics. Therefore, we used a porcine model of RV ischemia and reperfusion (IR) injury to study the influence of milrinone, levosimendan and dobutamine on the extent and degree of myocardial injury. METHODS: IR injury was induced by temporary ligation of the distal right coronary artery for 90 min, followed by 120 min of reperfusion. Treatment was initiated 30 min after coronary artery occlusion. A bolus of milrinone (n=12; 50 microg/kg) and levosimendan (n=10; 24 microg/kg) was applied in different groups, followed by continuous infusion of the drugs at 0.5 and 0.2 microg/kg/min, respectively. The effects on myocardial injury and inflammation were compared with a control (n=12) and a dobutamine group (n=10), where treatment was started with an infusion of 5 microg/kg/min. RESULTS: Milrinone and levosimendan reduced the resulting infarct size with respect to the area at risk (41.7+/-10.2%, 45.7+/-8.1%) when compared with the control group (58.3+/-6.1%). In contrast, dobutamine had no effect (55.8+/-7.7%). All drugs reduced the number of neutrophils infiltrating into the different myocardial regions and the circulating levels of interleukin-6. Increased levels of tumor necrosis factor alpha during reperfusion were only abated by milrinone and levosimendan. CONCLUSIONS: Cardioprotective properties of milrinone and levosimendan were demonstrated for the first time in a clinically relevant model of RV infarction.

[Perioperative management of patients with obstructive sleep apnoea]. / Perioperatives Management der obstruktiven Schlafapnoe.

There is lack of studies investigating procedures aiming at a decrease in perioperative mortality in patients with obstructive sleep apnoea (OSA). During anesthetic evaluation, identification of patients with OSA as well as using a risk score has been recommended by the American Society of Anesthesiology in order to identify the best perioperative strategy. Perioperative attention should be focused on a secure airway and the duration of monitoring that is necessary regarding severity of OSA, surgical stress and respiratory function. Postoperatively, residual neuromuscular blockade and a supine position have to be avoided. Continuous pulse oximetry should be used as long as patients remain at increased risk and should be applied until oxygen saturation remains above 90% with room air during sleep. Opioids should be excluded for pain management whenever possible, and CPAP or NIPPV should be administered as soon as feasible after surgery to patients who have been receiving it preoperatively.

Xenon: recent developments and future perspectives.

The noble gas xenon exerts favorable anesthetic properties along with remarkable hemodynamic stability in healthy patients undergoing elective surgery. Recent investigations documented that it does not prolong the duration of widely used neuromuscular blocking agents, including mivacurium and rocuronium. Some studies also suggest reduced neurocognitive compromise in the very early phase after general anesthesia. These properties differ from those observed for conventional inhalational anesthetics like isoflurane, desflurane and sevoflurane. However, a wider use of xenon in daily clinical routine has been limited owing to its higher price and technical restraints regarding economic delivery. Although there are controversial opinions, xenon seems to exert its main anesthetic features via the glutamate receptor. Recently, a novel binding cavity on the NMDA-subtype glutamate receptor has been elucidated that is occupied by xenon as well as isoflurane. Studies utilizing advanced imaging technologies have furthermore revealed that xenon markedly suppresses cerebral blood flow and glucose metabolism in distinct regions of the human brain. These investigations promise to further the understanding of the basic mechanisms underlying the induction and maintenance of anesthesia in general. Results from in vitro studies and various animal models have consistently demonstrated organoprotective properties of xenon, mainly in settings of ischemia and reperfusion injury. Interestingly, these effects have frequently been observed at subanesthetic concentrations and seem to be synergistic when used in combination with therapeutic hypothermia. Future studies will have to prove whether the high costs of xenon administration might be outweighed by its ability to substantially reduce the sequelae of myocardial and cerebral ischemia.

Establishment of a porcine right ventricular infarction model for cardioprotective actions of xenon and isoflurane.

BACKGROUND: Right ventricular (RV) function is an important determinant of post-operative outcome. Consequences of RV infarction might be limited by pre-conditioning with volatile anesthetic drugs. Therefore, we used a porcine model of RV ischemia and reperfusion (IR) injury to study the influence of isoflurane and xenon on the extent and degree of myocardial injury. METHODS: IR injury was induced by a 90-min ligation of the distal right coronary artery and 120-min reperfusion in thiopental anesthetized pigs. A control group (n=12) was compared with two groups, which received either 0.55 minimum alveolar concentration (MAC) isoflurane (n=10) or xenon (n=12) starting 60 min before ischemia. Myocardial injury was described by three criteria: the infarct size related to area at risk (IS/AAR), the infiltration of neutrophils as determined by myeloperoxidase (MPO) activity, and the plasma levels of tumor necrosis factor alpha (TNFalpha), interleukin 6 (IL-6), myoglobin and troponin-T (TnT). RESULTS: IS/AAR was reduced from 58.3+/-6.2% in the control group to 41.8+/-7.8% after isoflurane and 42.7+/-8.5% after xenon pre-treatment, which equals an absolute reduction of 16.5% [95% confidence interval (CI): 10.9-22.1] and 15.5% (95% CI: 10.1-20.9). The maximum increase of TnT could be observed within the xenon group. Both treatment groups were characterized by lower MPO activity, in the infarct and periinfarct region and lower plasma concentrations of TNFalpha and IL-6. CONCLUSIONS: It could be demonstrated for the first time in a model of RV infarction that the continuous application of isoflurane or xenon before, during and after ischemia reduced the extent (size) and severity (inflammation) of myocardial injury.

A comparison of waste gas concentrations during xenon or nitrous oxide anaesthesia.

BACKGROUND AND OBJECTIVE: The aim of this study was to compare waste gas concentrations during xenon or nitrous oxide anaesthesia. METHODS: A total of 64 patients were included in this study. Gas concentrations were measured with a mass spectrometer during anaesthesia. The probes were taken beside the patient's head and thorax and at a height of 180 cm above and at the floor level. RESULTS: In both groups, waste gas concentrations peak after intubation and extubation. Waste gas levels during xenon anaesthesia are low compared with nitrous oxide. CONCLUSIONS: The low waste gas levels of xenon seem to be beneficial compared to nitrous oxide.

Xenon or propofol anaesthesia for patients at cardiovascular risk in non-cardiac surgery.

BACKGROUND: The results of two European multi-centre trials on xenon anaesthesia led to the hypothesis that a xenon-based anaesthetic would keep left ventricular (LV) and circulatory function more stable than a propofol-based anaesthetic, in patients with coronary artery disease (CAD). METHODS: In a prospective, randomized design, 40 patients of ASA classes III and IV with known CAD were anaesthetized for elective non-cardiac surgery with either xenon (n=20) or propofol (n=20), each combined with remifentanil. Target criteria were intraoperative LV function as evaluated by transoesophageal echocardiography (TOE: Tei index, circumferential fibre shortening), arterial pressure, and heart rate (HR). RESULTS: Mean arterial pressure was decreased with propofol but was stable at pre-anaesthetic level with xenon (P<0.02) and HR was lower with xenon (P<0.01). The Tei index (also known as myocardial performance index) improved from 0.53 (0.14) to 0.45 (0.10) after 1 h with xenon and changed from 0.50 (0.14) to 0.55 (0.20) with propofol anaesthesia [means (SD); P=0.01 between the groups]. Deviation of circumferential fibre shortening from expected value after 1 h was -2 (14)% with xenon and -14 (18)% with propofol [means (SD); P=0.03]. There were no perioperative signs of acute myocardial ischaemia (TOE, ECG, and troponin T release). CONCLUSIONS: Xenon anaesthesia provided a higher arterial pressure level than propofol, with no signs of cardiovascular compromise, in patients with CAD. Echocardiographic indices showed better LV function with xenon.

An epidemiological study of the role of chrysotile asbestos fibre dimensions in determining respiratory disease risk in exposed workers.

BACKGROUND: Evidence from toxicological studies indicates that the risk of respiratory diseases varies with asbestos fibre length and width. However, there is a total lack of epidemiological evidence concerning this question. METHODS: Data were obtained from a cohort mortality study of 3072 workers from an asbestos textile plant which was recently updated for vital status through 2001. A previously developed job exposure matrix based on phase contrast microscopy (PCM) was modified to provide fibre size-specific exposure estimates using data from a re-analysis of samples by transmission electron microscopy (TEM). Cox proportional hazards models were fit using alternative exposure metrics for single and multiple combinations of fibre length and diameter. RESULTS: TEM-based cumulative exposure estimates were found to provide stronger predictions of asbestosis and lung cancer mortality than PCM-based estimates. Cumulative exposures based on individual fibre size-specific categories were all found to be highly statistically significant predictors of lung cancer and asbestosis. Both lung cancer and asbestosis were most strongly associated with exposure to thin fibres (<0.25 microm). Longer (>10 microm) fibres were found to be the strongest predictors of lung cancer, but an inconsistent pattern with fibre length was observed for asbestosis. Cumulative exposures were highly correlated across all fibre size categories in this cohort (0.28-0.99, p values <0.001), which complicates the interpretation of the study findings. CONCLUSIONS: Asbestos fibre dimension appears to be an important determinant of respiratory disease risk. Current PCM-based methods may underestimate asbestos exposures to the thinnest fibres, which were the strongest predictor of lung cancer or asbestosis mortality in this study. Additional studies are needed of other asbestos cohorts to further elucidate the role of fibre dimension and type.