Feasibility of continuous bronchoscopy during exercise in the assessment of large airway movement in healthy subjects.

Excessive dynamic airway collapse (EDAC) is a recognized cause of exertional dyspnea arising due to invagination of the trachea and/or main bronchi. EDAC is typically assessed by evaluating large airway movement with forced expiratory maneuvers. This differs from the respiratory response to exercise hyperpnea. We aimed to evaluate large airway movement during physical activity, with continuous bronchoscopy during exercise (CBE), in healthy subjects and compare findings with resting bronchoscopic maneuvers and imaging techniques. Twenty-eight individuals were recruited to complete two visits including treadmill-based CBE, to voluntary exhaustion, and cine magnetic resonance imaging (MRI) with forced expiratory maneuvers at rest. Twenty-five subjects [aged 29 (26-33) yr, 52% female] completed the study (n = 2 withdrew before bronchoscopy, and one was unable to tolerate insertion of bronchoscope). The majority (76%) achieved a peak heart rate of >90% predicted during CBE. The procedure was prematurely terminated in five subjects (n = 3; elevated blood pressure and n = 2; minor oxygen desaturation). The CBE assessment enabled adequate tracheal visualization in all cases. Excessive dynamic airway collapse (tracheal collapse ≥50%) was identified in 16 subjects (64%) on MRI, and in six (24%) individuals during resting bronchoscopy, but in no cases with CBE. No serious adverse events were reported, but minor adverse events were evident. The CBE procedure permits visualization of large airway movement during physical activity. In healthy subjects, there was no evidence of EDAC during strenuous exercise, despite evidence during forced maneuvers on imaging, thus challenging conventional approaches to diagnosis.NEW & NOTEWORTHY This study demonstrates that large airway movement can be visualized with bronchoscopy undertaken during vigorous exercise. This approach does not require sedation and permits characterization of the behavior of the large airways and the tendency toward collapse during upright, ambulatory exercise. In healthy individuals, the response pattern of the large airways during exercise appears to differ markedly from the pattern of airway closure witnessed during forced expiratory maneuvers, assessed via imaging.

No sex differences in oxygen uptake or extraction kinetics in the moderate or heavy exercise intensity domains.

The integrative response to exercise differs between sexes, with oxidative energy contribution purported as a potential mechanism. The present study investigated whether this difference was evident in the kinetics of oxygen uptake (V̇o2) and extraction (HHb + Mb) during exercise. Sixteen adults (8 males, 8 females, age: 27 ± 5 yr) completed three experimental visits. Incremental exercise testing was performed to obtain lactate threshold and V̇o2peak. Subsequent visits involved three 6-min cycling bouts at 80% of lactate threshold and one 30-min bout at a work rate of 30% between the lactate threshold and power at V̇o2peak. Pulmonary gas exchange and near-infrared spectroscopy of the vastus lateralis were used to continuously sample V̇o2 and HHb + Mb, respectively. The phase II V̇o2 kinetics were quantified using monoexponential curves during moderate and heavy exercise. Slow component amplitudes were also quantified for the heavy-intensity domain. Relative V̇o2peak values were not different between sexes (P = 0.111). Males achieved ∼30% greater power outputs (P = 0.002). In the moderate- and heavy-intensity domains, the relative amplitude of the phase II transition was not different between sexes for V̇o2 (∼24 and ∼40% V̇o2peak, P ≥ 0.179) and HHb + Mb (∼20 and ∼32% ischemia, P ≥ 0.193). Similarly, there were no sex differences in the time constants for V̇o2 (∼28 s, P ≥ 0.385) or HHb + Mb (∼10 s, P ≥ 0.274). In the heavy-intensity domain, neither V̇o2 (P ≥ 0.686) or HHb + Mb (P ≥ 0.432) slow component amplitudes were different between sexes. The oxidative response to moderate- and heavy-intensity exercises did not differ between males and females, suggesting similar dynamic responses of oxidative metabolism during intensity-matched exercise.NEW & NOTEWORTHY This study demonstrated no sex differences in the oxidative response to moderate- and heavy-intensity cycling exercise. The change in oxygen uptake and deoxyhemoglobin were modeled with monoexponential curve fitting, which revealed no differences in the rate of oxidative energy provision between sexes. This provides insight into previously reported sex differences in the integrative response to exercise.

The ONTAI study - a survey on antimicrobial dosing and the practice of therapeutic drug monitoring in German intensive care units.

PURPOSE: Optimization of antibiotic therapy is still urgently needed in critically ill patients. The aim of the ONTAI survey (online survey on the use of Therapeutic Drug Monitoring of antibiotics in intensive care units) was to evaluate which strategies intensive care physicians in Germany use to improve the quality of antibiotic therapy and what role a Therapeutic Drug Monitoring (TDM) plays. METHODS: Among the members of the German Society for Anaesthesiology and the German Society for Medical Intensive Care Medicine and Emergency Medicine, a national cross-sectional survey was conducted using an online questionnaire. RESULTS: The questionnaire was completely answered by 398 respondents. Without TDM, prolonged infusion was judged to be the most appropriate dosing regimen for beta lactams. A TDM for piperacillin, meropenem and vancomycin was performed in 17, 22 and 75% of respondents, respectively. For all beta lactams, a TDM was requested more often than it was available. There was great uncertainty as to the optimal pharmacokinetic/pharmacodynamic index for beta-lactams. 86% of the respondents who received minimal inhibitory concentrations adapted the therapy accordingly. CONCLUSION: German intensive care physicians are convinced of TDM for dose optimization. However, practical implementation, the determination of MICs and defined target values are still lacking.

New application for haplotype-specific extraction: Separation of mitochondrial DNA mixtures.

A particularly challenging aspect of forensic casework is the accurate interpretation of samples that contain DNA from more than one contributor, since DNA analysis of specific identification markers often results in ambiguous mixed profiles. Physically separating the various haploid components of a diploid or polyploid DNA sample or of a specimen containing DNA from multiple individuals can resolve this problem. We adapted and combined previously developed methods of haplotype-specific extraction (HSE) to separate and analyze mitochondrial DNA (mtDNA) in samples containing DNA from two individuals. After optimizing conditions and probes, we performed HSE to separate mitochondrial DNA mixtures, which manifest as mixed nucleotide calls at single base positions. We were able to subsequently identify the DNA of the two individuals by sequencing. Based on our findings from this proof-of-concept experiment, this novel assay will be useful for distinguishing among the mtDNA of individuals in mixed DNA samples.

[Quality assurance of rehabilitation by the German pension insurance: an overview]. / Ein aktueller Überblick zur Reha-Qualitätssicherung der Rentenversicherung.

The German pension insurance has in recent years developed a comprehensive programme for quality assurance in rehabilitation, and has implemented the programme into routine practice. Different aspects of rehabilitation are evaluated with differentiated instruments. Issues dealt with inter alia include the quality of rehabilitative care in a narrower sense, the structure and organisation of the rehabilitation centres, as well as quality from the patients' perspective. On the whole, positive results predominate. Big differences in quality however have been found between the rehabilitation centres. The data collections and data evaluations carried out make a continuous process of quality assurance reporting possible for use by rehabilitation centres and pension insurance agencies. This will enable targeted initiatives for quality improvement. The methods and procedures of quality assurance are enhanced at regular intervals, and the scope of quality assurance is extended. Thus, rehab quality assurance is also expanded to cover ambulant rehabilitation or rehabilitation of children and young people.

[Peri-operative adjustment and treatment of diabetes mellitus]. / Perioperative Einstellung und Behandlung des Diabetes mellitus.

In all disciplines of operative medicine the number of patients who suffer from diabetes mellitus is increasing dramatically. The reason is that nowadays up to 10% of the population is suffering from this disease. These patients must be treated with respect to the diabetes and also subsequent related conditions to prevent peri-operative complications. A special problem is that many patients do not know that they are suffering from diabetes. Pre-operatively and during the peri-operative course the coordinated efforts of surgeons, anaesthesiologists and diabetes specialists are essential to reach an optimal result. In all hospitals obligatory algorithms must be established for the treatment of these patients.

High potassium-induced activation of choline-acetyltransferase in human neocortex: implications and species differences.

The role of electrical and potassium (K(+))-induced depolarisation on choline-acetyltransferase (ChAT) activity in human and mouse neocortical slices was studied. When [3H]-ACh release was evoked by two K(+) stimulations in human neocortex, the mean S(2)/S(1) ratio was significantly below unity. ChAT inhibitors, like bromo-acetylcholine and ocadaic acid, raised this ratio by 79 and 63%, respectively, suggesting that the diminished S(2)/S(1) value in the absence of ChAT inhibitors reflected an increased ChAT activity at S(2) following K(+) depolarisation at S(1). When stimulated electrically, however, the S(2)/S(1) ratio in human neocortex was near unity and ocadaic acid remained without effect. In parallel experiments on mouse neocortical slices, the S(2)/S(1) ratio was near unity in both electrically or K(+)-evoked [3H]-ACh release and was not altered by ChAT inhibition. ChAT activity following K(+) depolarisation was also determined directly. ChAT activation in human neocortical slices was highest at 10 and 20mM K(+). ChAT activity in mouse neocortical tissue was not altered by K(+) depolarisation. These results suggest that in human, but not in mouse, neocortex ChAT activity may be increased due to ongoing K(+) depolarisation. This increase of ChAT activity supports a cholinergic degeneration hypothesis which has been entitled "autocannibalism" by Wurtman [TINS 15 (1992) 177].

Subarachnoid haemorrhage.

A high percentage of the population has aneurysms of the cerebral vessels, which are detected only by chance or after spontaneous rupture. Subarachnoid haemorrhage is still a problem because of high morbidity and mortality. Many patients do not fully recover neurologically and suffer from physical and psychosocial symptoms. The aims of treatment are to prevent the patient from rebleeding and to prevent secondary neurological damage. Whereas in former times, clipping of the aneurysm was often delayed for days or weeks, early operative intervention is the rule today, if the patient is not moribund and if there is no significant cerebral oedema. The anaesthetist can support the neurosurgeon with a spectrum of different methods of anaesthesia and monitoring, individually tailored to the needs of the patient. Most important, however, is a stable haemodynamic status, stable and normal intracranial pressure and a sufficient cerebral perfusion pressure. Vasospasm is still the main problem, as is early rebleeding. To treat this, nimodipine is the drug of choice combined with volume therapy, a slightly elevated cardiac output and a modestly elevated blood pressure.

Postoperative alpha 2-adrenergic stimulation attenuates protein catabolism.

The metabolic effects of continuous intravenous (IV) application of the alpha 2 agonist clonidine were evaluated by assessment of nitrogen economy and postaggression endocrine patterns. Twenty-four patients undergoing abdominothoracic esophageal cancer resection were studied. Thirteen of these patients with alcohol abuse were treated postoperatively with IV clonidine for prevention of alcohol withdrawal syndrome. Eleven patients who were not treated with clonidine served as controls. All patients were treated in a standardized manner in regard to surgical technique, balanced anesthesia, and postoperative intensive care treatment, including thoracic epidural analgesia with bupivacaine and fentanyl. Isonitrogenous and isocaloric nutrition was comparable in all patients. A significantly improved cumulated 6-day nitrogen balance was found in clonidine-treated patients (-1.5 +/- 4.9 g nitrogen) compared to the control group (-17.6 +/- 4.2 g nitrogen) (P < 0.05). The main reason for improved nitrogen economy may be clonidine-induced growth hormone (GH) release. The pattern of insulin-like growth factor I (IGF-I) and insulin-like growth factor binding protein 3 (IGFBP-3) concentrations could support this hypothesis.

Dexamethasone-induced sodium influx in human lymphocytes.

We evaluated the direct effects of glucocorticoids on intracellular sodium content and cellular transport systems. Cytosolic free sodium concentration ([Na+]i) was measured in intact human lymphocytes using the sodium-sensitive fluorescent dye sodium-binding benzofuran-isophthalate. Administration of dexamethasone for 60 min increased lymphocytic [Na+]i from 17.6 +/- 2.0 mmol/L to 24.3 +/- 3.9 nmol/L (n = 12; P < 0.01). The dexamethasone-induced [Na+]i increase was abolished in the absence of extracellular sodium, by mifepristone and by actinomycin D. The dexamethasone-induced [Na+]i increase was also seen after inhibition of Na+,K(+)-ATPase by 1 mmol/L ouabain. The present results indicate that dexamethasone produces a trans-plasma membrane sodium influx probably by early occurring genomic effects.

[Glucose-xylitol 35% (1:1) versus glucose 40%. Effectiveness and metabolic effects after major surgery]. / Glukose-Xylit 35% (1:1) versus Glukose 40%. Effektivität und metabolische Auswirkungen nach grossen operativen Eingriffen.

Injury and stress are accompanied by a characteristic hormonal response and altered energy utilisation. Hyperglycaemia and negative nitrogen (N) balance are the leading symptoms of the metabolic changes in the post-operative state. In a prospective, randomised study the efficacy and metabolic effects of glucose-xylitol (GX) 35% (1:1) versus glucose (G) 40% were investigated in patients undergoing major surgery. METHOD. Twenty-four patients undergoing abdomino-thoracic oesophageal cancer surgery were treated in a standardised manner. Total parenteral nutrition was administered over 6 days (kg body wt.-1/day): day of surgery 1-1.25 g carbohydrate (CH); 1st postoperative day (POD) 1.5 g CH, 1 g amino acids (AA); 2nd POD 3 g CH, 1.5 g AA, 1.0 g fat; from 3rd POD 3 g CH, 1.5 g AA, 1.5 g fat (CH GX35% (n = 12) or G40% (n = 12), AA Intrafusin 15%, fat Intralipid 20%). Daily and cumulative N balances, blood-G profiles, blood chemistry, and physical parameters were determined. Glucagon and insulin profiles, CH losses, and oxalic acid secretion were measured. RESULTS. Both groups were comparable for age, body mass index, clinical and physical parameters, and blood chemistry. Mean cumulative N balances after 6 days were -12.0 +/- 16.3 g N for GX35% and -5.6 +/- 19.4 g N for G40% (n.s.; Wilcoxon, P < 0.05). Blood G was similar for both groups with values ranging from 130 to 240 mg/dl on the day of surgery and below 150 mg/dl on the consecutive days. In each group 1 patient needed additional insulin therapy. Glucagon and insulin levels did not show a significant difference between the groups. CONCLUSION. No difference in tolerance and efficacy of nutritional support by GX versus G at a dose of 3 g.kg body wt.-1.d in oesophagectomised patients could be observed. Similar blood G profiles were in accordance with comparable glucagon and insulin levels. Because of the high standard deviations of N balances, differences in efficacy could not be proven. A significantly lower level of pseudocholinesterase (PCHE) for G40% on day 7 might indicate enhanced hepatic protein synthesis in the GX group.

The influence of different procedures of general anaesthesia on platelet function, coagulation and the fibrinolytic system.

We investigated whether different procedures during general anaesthesia alter platelet activation in vivo and/or activate coagulation and fibrinolysis. Forty-one healthy adult patients, scheduled for elective ophthalmic surgery under general anaesthesia, were studied with regard to changes of plasma beta-thromboglobulin (beta TG, index of platelet activation), thrombin-antithrombin III-complex (TAT, index of activation of coagulation) and d-dimer (index of fibrinolysis) during anaesthesia. The patients underwent either inhalation anaesthesia with enflurane and nitrous oxide or balanced anaesthesia with enflurane (0.5% end-tidal concentration) and alfentanil. Ten minutes after intubation the beta TG level was significantly reduced compared to the preoperative value in both general anaesthesia groups. Balanced anaesthesia caused a moderate but significant increase of TAT values at 10 min after extubation. No significant change in d-dimer levels was seen. Presuming a minimal effect of the surgical procedure on the determined variables, we conclude that none of the anaesthetic procedures induces platelet activation and fibrinolysis. The clinical relevance of the moderate coagulation activation during balanced anaesthesia remains to be investigated.