Beneficial Metabolic Effects of Duodenal Jejunal Bypass Liner for the Treatment of Adipose Patients with Type 2 Diabetes Mellitus: Analysis of Responders and Non-Responders.

Implantation of a duodenal-jejunal endoluminal bypass liner (DJBL) has shown to induce weight loss and to improve metabolic parameters. DJBL is a reversible endoduodenal sleeve mimicking duodenal bypass while lacking risks and limitations of bariatric surgery.Effects on metabolic control, body mass parameters, appetite regulation, glucose tolerance, organ health, and lipid profile were determined in 16 morbidly overweight patients with type 2 diabetes mellitus. In addition, relevant hormones (leptin, ghrelin, gastric inhibitory peptide, glucagon-like peptide, and insulin) were measured by enzyme-linked immunosorbent assay (ELISA) and chemiluminescent microparticle immunoassay (CMIA) at 0, 1, 32, and 52 weeks post-implant following a mixed meal tolerance test. Lipoprotein subclasses were analysed by proton nuclear magnetic resonance (1H NMR) spectrometry. DJBL provoked weight loss, a decrease in fat mass, and an improvement in insulin resistance and hepatic function in most but not all of the patients, but in the long term did not increase gut hormone fasting levels pointing to a combined effect of more than gut parameters alone. Lipidome analysis was done in 10 patients, allowing classification to responders and non-responders by reduction of sLDL-p subfraction; and to further analyse the atherogenic profile. Responders showed an overall more pronounced effect regarding improvement of HbA1c, BMI, and HOMA index.Implantation of a DJBL in obese type 2 diabetes patients does not per se lead to an improvement of the metabolic situation. Further analyses including larger cohorts have to be performed to identify responding patients, to better treat non-responders and to analyse the key effectors.

[Proteome-based diagnostic and prognostic biomarkers of prostate cancer]. / Proteombasierte diagnostische und prognostische Biomarker beim Prostatakarzinom.

BACKGROUND: Due to comprehensive PSA screening, the incidence for prostate cancer (PCa) is rising. Therefore, there is an urgent need for improved PCa diagnostics and prognostic tools to differentiate between insignificant and aggressive, fast growing tumors. METHODS: With the proteome-based method presented here, we were able to distinguish PCa from BPH, chronic prostatitis and healthy controls with 83 % sensitivity and 67 % specificity. Furthermore, the methods discerned advanced PCa from local, organ-confined PCa in a group of patients with gleason score 7 (80 % sensitivity, 82 % specificity). RESULTS: Our proteomic approach is based on the analysis of low molecular weight polypeptides, identified as the endpoint of the naturally occuring liquefaction cascade in seminal plasma. For the first time using seminal plasma as a source, we analysed a complex network of interacting proteases and specific inhibitors, reflecting tumor biology specificity. Our diagnostic and prognostic tool is robust and easy to handle, and therefore it is well suitable for the laboratory and medical practice.

Proteomics in hypertension.

Proteomics, the study of the proteins making up the proteome, has emerged in recent years as an important tool in several different fields of medical research for early disease detection, for assessment of response to treatment and for unravelling underlying pathophysiological mechanisms. Although the majority of patients with hypertension are treated in a similar manner, the causes underlying the condition are diverse, and often poorly understood. Genetic studies have implicated several different candidate genes, but it may be that examination of the 'downstream' products of genes, the proteins, will help to improve understanding of the link between the environmental and genetic effects that contribute towards development of hypertension. Proteomic studies can be performed quickly and reliably on several different sample types including plasma and urine, requiring minimal pre-test preparation. In this review, we will compare the different analytical platforms and technical issues involved in proteomic analysis. We will discuss existing studies of proteomics in hypertension, as well as related conditions such as renal disease, pre-eclampsia and coronary artery disease. We will also explore potential future applications of proteomics-based research, which may ultimately lead to improved population screening, monitoring of therapy and early detection of target organ damage.

Clinical proteomics: current techniques and potential applications in the elderly.

In Western societies the process of aging is closely related to the onset of chronic diseases, such as coronary artery disease, diabetic nephropathy or different types of malignancies. Novel biomarkers are urgently needed to assist in managing these diseases. Parallel to technical advancements possibilities for the analysis of the human proteome for biomarkers have recently made considerable progress. In a first part, this article attempts to describe the main proteomic platform technologies, their advantages and disadvantages and will critically review proteomic study design aspects necessary to obtain valuable data, such as choosing suitable clinical specimens, data processing and mining. Physiological age-related alterations in the human proteome have been described and were similar to indolent changes associated with chronic diseases, in particular of the kidneys. Therefore, in a second part this review will introduce several examples for the application of clinical proteomics to aging itself and age-related diseases. Several recent proteome studies with clinically sound designs are available. These performed careful validation in blinded cohorts. It is anticipated that a boost in disease-related proteomic data is expected in the very near future. However, lessons of the past teach the strict adherence to proper technological approaches, appropriate statistics, and large databases to fulfil these high expectations.

[Urinary proteomics: the diagnostic key for urinary tract abnormalities and kidney diseases in children?]. / Urinproteomanalytik : Der Diagnoseschlüssel bei Harntransportstörungen und Nierenerkrankungen im Kindesalter?

Due to its accessibility and availability, ease of collection, and correlation with physiology and pathology, urine is an attractive source for clinical proteomics/peptidomics in urology and nephrology. Here, we review the published findings of a reproducible, high-resolution method for peptidome analysis of naturally occurring human urinary peptides and proteins - ranging from 0.8 to 17.0 kDA - using samples from renal patients analyzed by capillary electrophoresis coupled to mass spectrometry (CE-MS). CE-MS identified children with urodynamically relevant ureteric junction obstruction, vesicoureteric reflux of grades IV and V, glomerulopathies, tubulopathies, and chronic kidney disease. Our analysis revealed that the incorporation of urinary proteome analysis in the initial evaluation of children with urinary tract abnormalities will avoid side effects of radiological imaging techniques, reduce costs, and increase the quality-adjusted life years in this patient population. CE-MS can be recommended for clinical prospective studies on the analysis of naturally occurring urinary peptides in children with urinary tract diseases.

[Outpatient surgery: an unstoppable evolution]. / Chirurgie ambulatoire: une voie incontournable.

The trend is to definitely shorten hospital stays. It follows in the footsteps of a broader range of surgeries that can be managed in an ambulatory care setting. The expected benefits are: a reduction in costs, a shorter preoperative delay, a shorter absence for the work place and a lessened risk of hospital-borne infections. A multidisciplinary approach is essential for the success of such a program. Surgeons, anaesthetists and nursing staff must be prepared to modify and adapt their skills. The criterion of success for such an endeavour is a low level of readmissions and hospitalisations. If day surgery tends to keep the patient away for the hospital settings, it certainly places him in the centre of his medical management.

Proteomics in gerontology: current applications and future aspects--a mini-review.

BACKGROUND: Aging is closely related to the onset of chronic diseases, such as coronary artery disease, diabetic nephropathy or different types of malignancies, reflecting the demand for novel biomarkers to manage theses diseases. OBJECTIVE: The analysis of the human proteome for biomarkers has made considerable advances in the last years. METHODS: We describe the main technological approaches taken, their advantages and disadvantages. RESULTS: We will review the different clinical sources of material and attempt to highlight the different challenges and approaches associated with these. Age-related changes in the proteome have been described and were found to be highly similar to changes associated with chronic diseases. We will give several examples on the successful application of proteomics in the diagnosis, prognosis and therapy of these chronic diseases. CONCLUSIONS: A boost in disease-related proteomic information is expected in the very near future, and will also result in its broad clinical application. However, this view appears to be dependent on the strict adherence to proper technological/analytical parameters, correct statistics, and large databases that allow comparison of datasets provided by different scientists. Clearly, the proteome is by far too complex to be tackled by one laboratory on its own.

Comparison of the Glidescope, the McGrath, the Airtraq and the Macintosh laryngoscopes in simulated difficult airways*.

SUMMARY: Several indirect laryngoscopes have recently been developed, but relatively few have been formally compared. In this study we evaluated the efficacy and the usability of the Macintosh, the Glidescope, the McGrath and the Airtraq laryngoscopes. Sixty anaesthesia providers (20 staff, 20 residents, and 20 nurses) were enrolled into this study. The volunteers intubated the trachea of a Laerdal SimMan manikin in three simulated difficult airway scenarios. In all scenarios, indirect laryngoscopes provided better laryngeal exposure than the Macintosh blade and appeared to produce less dental trauma. In the most difficult scenario (tongue oedema), the Macintosh blade was associated with a high rate of failure and prolonged intubation times whereas indirect laryngoscopes improved intubation time and rarely failed. Indirect laryngoscopes were judged easier to use than the Macintosh. Differences existed between indirect devices. The Airtraq consistently provided the most rapid intubation. Laryngeal grade views were superior with the Airtraq and McGrath than with the Glidescope.

[Ischaemic cholestasis in intensive care unit]. / La cholestase ischémique en réanimation.

Cholestasis is frequently encountered in the ICU and is associated with a poor outcome. Ischaemia should be considered among the numerous aetiologic factors that may trigger cholestasis in the ICU. Blood supply to biliary tract is mainly provided by the hepatic artery, throughout a peribiliary vascular plexus. Interruption of the hepatic artery blood supply leads to cholestasis with a concomitant proliferative biliary reaction. Bile duct proliferation persists, while bile flow restores and biologic cholestasis syndrome spontaneously resolves in several weeks. Liver fibrosis related to the activation of periportal mesenchymental cells is observed in the close vicinity of proliferative bile ducts. Ischaemic cholestasis can be ascribed, at least partly, to hypoxia-induced disorders in the expression of hepatocytes biliary salts membrane transporters.

Laparoscopic colon surgery: unreliability of end-tidal CO2 monitoring.

BACKGROUND: The relatively good haemodynamic and respiratory tolerance to abdominal CO(2) insufflation has mostly been observed in healthy patients during short-lasting laparoscopic procedures. End-tidal CO(2) pressure (PetCO(2)) has been shown to be a reliable method to assess arterial CO(2) (PaCO(2)) in the absence of cardio-respiratory disease in this setting. However, no study has investigated whether PetCO(2) is accurately related to PaCO(2) during laparoscopic colon surgery. Indeed, these procedures last longer, prolonging the pneumoperitoneum and requiring a Trendelenburg position. The aim of the present study was to measure the PaCO(2)-PetCO(2) difference over time in patients undergoing laparoscopic colon surgery and to determine whether PaCO(2) is reliably assessed by PetCO(2). METHODS: Forty consecutive patients (ASA I and II) scheduled for laparoscopic colon surgery were anaesthetized and ventilated to obtain a PetCO(2) between 4.0 and 5.5 kPa. After initiation of CO(2) insufflation, PaCO(2) and PetCO(2) were recorded every 30 min during surgery. RESULTS: No complication was observed during anaesthesia. The mean arterial pressure increased significantly after CO(2) insufflation and remained steady up to the end of pneumoperitoneum. The heart rate remained stable over time. The relation between PaCO(2) and PetCO(2) was not constant among patients and increased over time within the same patients. The R(2) values fluctuated and did not show a constant correlation between PaCO(2) and PetCO(2). CONCLUSION: The correlation between PaCO(2) and PetCO(2) during laparoscopic colon surgery is inconsistent mainly due to inter- and intra-individual variability.

[Capillary electrophoresis coupled to mass spectrometry for proteome analysis. An innovative diagnostic method for prostate and bladder cancer]. / Kapillarelektrophorese gekoppelte Massenspektrometrie zur Proteomanalyse. Eine innovative diagnostische Methode bei Prostata- und Blasenkrebs.

We developed a proteomics-based technology for the non-invasive detection of urothelial and prostate carcinoma. Using capillary electrophoresis coupled to mass spectrometry, disease-specific changes in the urinary proteome were detected and subsequently relevant polypeptides were employed as disease-specific biomarkers. Here we report the results of various studies including approximately 1,000 patients with different diseases and healthy volunteers. The results of these studies revealed that prostate and urothelial carcinoma can be detected by using disease-specific polypeptide patterns. Preliminary results also indicate that the tumour stage of an urothelial carcinoma can be estimated by this approach. In conclusion, this new and non-invasive application might help to improve the diagnostic methods already available.

Hepatopulmonary syndrome increases the postoperative mortality rate following liver transplantation: a prospective study in 90 patients.

Hepatopulmonary syndrome (HPS) is a frequent pulmonary complication of patients with end-stage liver diseases. HPS is diagnosed by hypoxemia and pulmonary vascular dilatation and is an independent risk factor of mortality. Orthotopic liver transplantation (OLT) is the only factor that modifies the natural course of HPS. Once patients with HPS have been transplanted, their long-term survival rate is similar to transplanted patients without HPS. Consequently, HPS is an indication of OLT whatever the severity of hypoxemia. However, besides the favorable long-term survival of HPS patients with OLT, a high postoperative mortality (mostly within 6 months) has been suggested. The aim of our study was to analyze the incidence of HPS and postoperative outcome after OLT in 90 consecutive patients. All patients were prospectively included and had blood gas analysis to detect HPS. Patients with hypoxemia had contrast echocardiography to confirm HPS. Nine patients had HPS with a 50 50 mmHg in all HPS patients transplanted.

Acute desflurane or sevoflurane exposure on a previously stabilized atracurium-induced neuromuscular block.

BACKGROUND AND OBJECTIVE: The aim of this prospective study was to compare the effect of the administration of desflurane or sevoflurane to a fixed neuromuscular block. METHODS: After written consent, 12 patients were anaesthetized with propofol and sufentanil. Atracurium was administered via a continuous infusion in order to obtain 85% twitch depression of the control value assessed by repeated accelerometric stimulation at the adductor pollicis. Once stabilized over the course of 30 min, propofol was discontinued and either desflurane (n = 6) or sevoflurane (n = 6) was delivered at 1 MAC in a mixture of 50% O(2) in air. Study parameters were the magnitude and the time of twitch height variations. Results are presented in mean +/- SD. RESULT: Exposure to halogenated agents led to a significant reduction in twitch height with similar magnitude between the two agents. However, interaction with desflurane showed an initial and transient rise (35 +/- 22%) in twitch height before subsequent depression occurred. The time to reach 50% of the signal depression in the desflurane group was significantly delayed (25 +/- 7 vs. 11 +/- 4 min in the sevoflurane group; P < 0.01). CONCLUSIONS: On a stable neuromuscular block elicited by continuous infusion of atracurium, the abrupt administration of desflurane or sevoflurane reduces the accelerometric responses of the adductor pollicis in a similar way. This potentiating effect is produced faster after sevoflurane than after desflurane. With desflurane, a biphasic effect (of a transient and moderate increase followed by depression of the signal) was recorded.

Root-cause analysis of an airway filter occlusion: a way to improve the reliability of the respiratory circuit.

BACKGROUND: To show how root-cause analysis can identify system-level factors causing critical incidents and accidents, we present an investigation of the occlusion of an airway filter during anaesthesia. METHOD: The investigation was based on a framework specifically developed for the analysis of medical accidents. This framework helped to identify the chronology and outcome of the case, the care management problems and the factors that led to the event. Information was obtained by interviewing the anaesthesiologist in charge of the patient. RESULTS: Occlusion was not recognized because the filter was hidden under the drapes and below the patient's head. To reduce the frequency of this event, we recommend that filters should be visible, placed above the level of the patient's body, or mounted on the expiratory circuit, at a distance from patient's airway. CONCLUSIONS: To allow appropriate corrective actions, critical incidents and accidents should be systematically investigated using root-cause analysis.

Assessing cerebrospinal fluid rhinorrhea: a two-dimensional electrophoresis approach.

Assessment of nasal cerebrospinal fluid (CSF) fistula commonly relies on the determination of CSF markers in an aqueous rhinorrhea, such as the beta2-transferrin immunofixation assay. While generally reliable, false positive and false negative results have been reported for most of the laboratory tests yet available. Based on the hypothesis that the simultaneous assessment of several CSF markers may yield an increased sensitivity and specificity, we used a proteomics, two-dimensional electrophoresis 2-DE based approach to study samples of nasal secretions obtained from 18 patients suspected of CSF rhinorrhea. Since CSF, nasal mucus and plasma may coexist in the nasal cavities, we first defined five specific markers for each of these biological fluids (transferrin, prostaglandin-D synthase, transthyretin, and two unknown trains of spots for CSF, immunoglobulin A (IgA) S-chain, lipocortin-1, lipocalin-1, prolactine-inducible protein and palatal lung nasal epithelium clone protein for mucus, haptoglobin alpha1/2- and beta-chains, fibrinogen alpha-, beta- and gamma-chains for plasma). Gels from the rhinorrhea patients were then compared to these 2-DE reference maps to determine the presence or absence of the defined markers, and clinical data were independently compared to the results of the 2-DE study. In all cases, the biological fluid(s) anticipated to be present in the nasal secretions based on clinical data were correctly identified by 2-DE. Moreover, an excellent correlation was found in nine patients who underwent extensive workup for suspected CSF rhinorrhea, since CSF was found by the 2-DE method in four patients in whom a CSF fistula was confirmed, whereas the test was negative in five patients in whom a CSF fistula was excluded. In the remaining patients, mucus, sometimes contamined with blood, was found to be the major component of the nasal secretions, confirming that clear mucus may mimick CSF rhinorrhea. These preliminary results suggest that a 2-DE-based multimarker approach is a valid, sensitive, and specific method to assess the presence of CSF in occult rhinorrhea.

Hepatic haemodynamic changes following inhibition of endothelium-derived relaxing and hyperpolarising factors in anaesthetised miniature pigs.

The influence of endothelium-dependent vasodilatation in regulating the hepatic circulation has been investigated by intraportal infusion of inhibitors of either endothelium-derived relaxing factor (NG-nitro-L-arginine-methyl-ester [L-NAME]) or of endothelium-derived hyperpolarising factor (ATP-dependent K(+)-channel inhibitor, glybenclamide) in barbiturate anaesthetised miniature pigs. Intraportal infusion of acetylcholine (5.5 micrograms kg-1 min-1 over 2 min) produced a selective 3-fold increase in hepatic artery and coeliac trunk blood flow, while mesenteric, portal, systemic, and pulmonary vascular beds remained unchanged. Intraportal L-NAME or glybenclamide did not reduce the hepatic artery and coeliac trunk flows but increased systemic and mesenteric vascular resistances. The acetylcholine-induced hepatic artery vasodilatation was partially blocked by 59%, 76% and 66% by L-NAME, at 30, 100, and 300 mg/kg respectively. Glybenclamide pretreatment up to 3 mg/kg did not modify acetylcholine-induced vasodilatation of the hepatic artery and coeliac trunk. Furthermore, prior cyclooxygenase inhibition did not alter the hepatic vascular response to acetylcholine. These results suggest that, in contrast to what is observed in large vessels, the hepatic vascular tree may not be entirely regulated by nitric oxide under basal conditions, but nitric oxide is released readily upon stimulation with acetylcholine, a response that is largely but incompletely blocked by L-NAME pretreatment. Neither basal vascular tone nor acetylcholine-induced vasorelaxation are mediated by the opening of glybenclamide-sensitive K+ channels in the hepatic circulation in pigs.

Hypocomplementemic panniculitis with paraprotein.

Two episodes of severe panniculitis accompanied by fever and an acute phase response were the main clinical features in a patient who had an unusual IgG kappa paraprotein. Both episodes responded promptly to steroids. Complement proteins of the early classical pathway were depleted in the patient's serum, and in vitro experiments indicated that the IgG kappa paraprotein activated complement directly. The association of recurrent panniculitis and paraproteinemia-hypocomplementemia has been described in 2 other patients. It should be recognized since its response to steroids is immediate.

Influence of sex on cerebrospinal fluid density in adults.

The extent of sensory block during spinal anaesthesia is unpredictable and is influenced by many factors, mainly patient position, site of injection, baricity and the dose of drug injected. Among other factors, cerebrospinal fluid (CSF) density has been advocated to affect subarachnoid distribution of local anaesthetics. In this study, we have investigated the influence of patient characteristics such as sex, age, weight and height on variations in the density of CSF in more than 46 consecutive patients undergoing spinal anaesthesia. CSF 2 ml was obtained after spinal puncture and before injection of local anaesthetic. Mean CSF density measured at 37 degrees C was mean 1.00054 (SD 0.00017) g ml-1, with significantly lower CSF densities in women (1.00049 (0.00011) g ml-1) than in men (1.00058 (0.00011) g ml-1) (P = 0.024). In contrast, there was no correlation between age, weight or height, and CSF density. These results suggest that sex significantly influenced CSF density and may therefore modify subarachnoid distribution of local anaesthetics.

Effects of fenoldopam on systemic and splanchnic haemodynamics and oxygen delivery/consumption relationship during hyperdynamic ovine endotoxaemia.

OBJECTIVE: To evaluate the use of a selective dopamine-1 agonist (fenoldopam) to provide selective splanchnic vasodilatation during sustained hypotensive endotoxaemia in sheep. DESIGN: Randomised, controlled, experimental study. SETTING: Animal research laboratory. SUBJECTS: 12 adult instrumented, midazolam-sedated sheep. INTERVENTIONS: The animals were randomised to receive a 20-min continuous infusion of dopamine (10 microg x kg(-1) x min(-1), fenoldopam (10 microg x kg(-1) x min(-1) and noradrenaline (1 microg x kg(-1) x min(-1)) under control conditions and 12 h after endotoxaemia was induced by a continuous infusion of Escherichia coli endotoxin producing a stable hyperdynamic state simulating human septic shock. This drug dosage was selected to produce a 25-30% increase in cardiac output by all three drugs during control conditions. MEASUREMENTS AND RESULTS: Systemic and splanchnic haemodynamic data were continuously obtained and systemic and splanchnic oxygen delivery (DO2) and consumption (VO2) were calculated. Hyperdynamic hypotensive endotoxaemia did not modify the splanchnic and renal reduction in DO2 and the vasoconstrictive reactivity to noradrenaline observed during control conditions. In contrast, endotoxaemia abolished the fenoldopam and dopamine-induced increase in splanchnic DO2 (especially in the coeliac trunk) observed during control conditions. CONCLUSIONS: During sustained hyperdynamic endotoxaemia, the dopaminergic-induced selective increase in coeliac trunk blood flow is abolished, most probably because of an already maximally vasodilated splanchnic circulation which prevented dopamine or fenoldopam to vasodilate this area further. Contrary to common belief, selective dopamine-1 agonist administration under these conditions may therefore not be beneficial to the splanchnic organs, though it improves whole body DO2 and VO2.