Is there a chronic sleep stage-dependent linear and nonlinear cardiac autonomic impairment in obstructive sleep apnea?

RATIONALE: Obstructive sleep apnea (OSA) is a respiratory disorder that has the potential to negatively impact heart rate variability (HRV) during the sleep cycle. However, it is uncertain whether there is a chronic sleep stage-dependent linear and nonlinear cardiac autonomic impairment in OSA. The aim of this study was to perform HRV analysis in apnea-free samples as well as during stage 2 and rapid eye movement (REM) sleep in mild and moderate OSA (MiOSA and MOSA, respectively) subjects as well as health controls (NonOSA). METHODS: This study included 20 MiOSA (37 ± 14 years), 20 MOSA (39 ± 8 years), and 18 NonOSA (36 ± 8 years) subjects. Subjects underwent in-laboratory overnight polysomnography with electrocardiography recording. HRV indices were obtained by analyzing the R-R intervals (RRis) in 5-min apnea-free samples by the linear frequency domain [low frequency (LF), high frequency (HF) and LF/HF], Poincaré plot [standard deviation (SD1) and (SD2)], recurrence plot [mean line length (Lmean)], recurrence rate (REC), determinism (DET), and Shannon entropy (ShanEn). RESULTS: The MOSA group presented with higher LF, LF/HF, and DET indices compared to NonOSA as well as a lower parasympathetic index (HF), suggesting sympathetic hyperactivity in MOSA subjects. Interestingly, MiOSA subjects failed to show the expected linear HRV difference between sleep stages, as observed in NonOSA, which may represent an early onset of autonomic impairment at this stage of OSA. CONCLUSION: In OSA patients, there is a chronic sleep stage-dependent impairment of linear and nonlinear cardiac autonomic modulation. Interestingly, this impairment may be identifiable during the early stages of the disease.

[Bringing clinical simulation into an Anesthesia residency training program in a university hospital. Participants' acceptability assessment]. / Inserción de la simulación clínica en el currículum de Anestesiología en un hospital universitario. Evaluación de la aceptabilidad de los participantes.

INTRODUCTION: Clinical simulation is currently an integral part of the curriculum of the Anesthesiology residency programs in other countries. We aimed to describe and evaluate the insertion of simulation in an anesthesia residency training program. METHODS: Activities feasible to be used for training in a simulated environment were classified into 2 modules: workshops for technical skills conducted with first year residents, and high fidelity simulation scenarios performed with second and third year residents. After each activity, and using an anonymous questionnaire, residents assessed their satisfaction and objectives accomplished. RESULTS: A total of 18 activities: 6 skills workshops and 12 high fidelity scenarios were assessed. A total of 206 questionnaires were analyzed, corresponding to 41 residents. Almost all (96%) of respondents agreed or strongly agreed that workshops met the objectives and should be mandatory in the anesthesia curriculum; however, 11% agreed that the activity caused anxiety and/or nervousness. The high fidelity scenarios were considered realistic and consistent with the objectives by 97% of residents, and 42% felt that workshops caused anxiety and/or nervousness. CONCLUSIONS: The inclusion of simulation has been well accepted by the residents. The activities have been described as realistic, and limited to the objectives, essential points in adult education, as according to Kolb's learning model this is associated with profound, useful and long lasting knowledge.

Evaluation of the effect of intravenous lidocaine on propofol requirements during total intravenous anaesthesia as measured by bispectral index.

BACKGROUND: I.V. lidocaine is increasingly used as an adjuvant during general anaesthesia. The aim of this study was to evaluate the effect of i.v. lidocaine in reducing propofol anaesthetic requirements during total i.v. anaesthesia (TIVA) maintenance and to evaluate its effect on early recovery from anaesthesia. METHODS: Forty adult patients undergoing elective laparoscopic cholecystectomy under TIVA were randomly allocated into the lidocaine group (administered 1.5 mg kg(-1) i.v. lidocaine over 5 min followed by 2 mg kg(-1) h(-1)) and the control group (administered an equal volume of saline). Propofol was administered using a target-controlled infusion to maintain the bispectral index values between 40 and 60. After surgery, all infusions were discontinued and the time to extubation was recorded. Serial arterial blood samples were drawn to assess drug plasma levels. RESULTS: The maintenance dose of propofol was significantly lower in the lidocaine group [6.00 (0.97) mg kg(-1) h(-1)] vs the control group [7.25 (1.13) mg kg(-1) h(-1); P=0.01]. Propofol plasma levels measured at the end of the infusion were 3.71 (0.89) µg ml(-1) in the lidocaine group and 3.67 (1.28) µg ml(-1) in the control group (P=0.91). The median time to extubation was longer (11.0 min; range: 10.0-21.0) in the lidocaine group vs the control group (8.3 min; range: 5.5-12.5; P=0.02). CONCLUSIONS: I.V. lidocaine reduces propofol requirements during the maintenance phase of TIVA, particularly during surgical stimulation. This sparing effect is associated with an increased time to extubation. Owing to its effect on early recovery from anaesthesia, i.v. lidocaine should be taken into account when used as a component of i.v. anaesthesia.

Developing an anti-Campylobacter jejuni vaccine.

The proteomics era allows for the definition of biological organisms at the protein level, offering new opportunities for delimiting the self- and non-self boundaries between microbes and the human host. Here, we apply proteomics to design a vaccine against the major pathogenic factor of Campylobacter jejuni, i.e. cytolethal distending toxin (CDT). We used the scientific rationale that only peptide sequences not represented in the host proteome have the potential to evoke powerful, non-cross-reactive immune responses, thereby guaranteeing effectiveness and safety.

Scaling properties of universal tetramers.

We evidence the existence of a universal correlation between the binding energies of successive four-boson bound states (tetramers), for large two-body scattering lengths (a), related to an additional scale not constrained by three-body Efimov physics. Relevant to ultracold atom experiments, the atom-trimer relaxation peaks for |a|→∞ when the ratio between the tetramer and trimer energies is ≃4.6 and a new tetramer is formed. The new scale is also revealed for a < 0 by the prediction of a correlation between the positions of two successive peaks in the four-atom recombination process.

Propofol consumption and recovery times after bispectral index or cerebral state index guidance of anaesthesia.

BACKGROUND: We compared the propofol requirements and recovery times when either the bispectral index (BIS) monitor or the cerebral state monitor (CSM) is used to guide propofol anaesthesia. METHODS: Forty patients undergoing laparoscopic cholecystectomy were studied. All patients were monitored with both monitors and were randomly allocated into two groups according to the monitor used to titrate propofol administration. Propofol was administered to maintain BIS or CSM within 40 and 60. Propofol consumption and clinical markers of recovery were assessed after surgery. RESULTS: In the CSM group, the values of cerebral state index (CSI) and BIS were 47 (5) and 38 (6), respectively (P=0.00054). In the BIS group, the values of CSI and BIS were 47 (5) and 45 (2), respectively (P=0.15). In the BIS group, the total amount of propofol used was lower [109 (20) microg kg(-1) min(-1)] than in the CSM group [130 (27) microg kg(-1) min(-1)] (P=0.018). The time to eye opening was lower in the BIS [7.2 (3.5) min] than in the CSM group [10.7 (6.6)] (P=0.038). There were no differences in fentanyl consumption, or in other clinical markers of recovery. CONCLUSIONS: Compared with BIS, propofol anaesthesia guided with CSI resulted in 20% higher propofol doses. This, however, does not lead to clinically relevant differences in recovery times.

[Blockade of B7:CD28 costimulatory pathway reduces the vascular damage in an experimental model of chronic rejection]. / Riduzione del danno vascolare in un modello sperimentale de rigetto cronico mediante blocco selettivo della via di costimolazione B7:CD28.

AIM: Costimulatory blockade and donor specific transfusion (DST) can catalyze tolerance of transplanted organs through a multistep adaptation between the recipient and donor immune systems. Such an in vivo process may prolong graft survival. Aim of this study was to evaluate the outcome of aortic transplantation under CTLA4Ig and DST in a mismatched model in rats. METHODS: Orthotopic aortic transplantation was performed in recipients Lewis from Wistar-Furth rats. The animals were stratified into 3 groups, according to the postoperative treatment. Group 1 had aortic transplantation only (controls, n=6), while group 2 (n=7) had a load of donor splenocytes (DST). Group 3 was treated with DST and CTLA4Ig. All the animals were sacrificed at the 60th postoperative day and the aortic specimens were prepared for histology. Intimal cells, muscular cells and lymphocyte cell infiltration were evaluated by serial counts. RESULTS: In Group 1 there was a severe chronic rejection, while group 2 showed a slower onset of chronic rejection with less inflammatory infiltrate than group 1 (P<0.05). Group 3 had the best overall outcome with lower infiltration and minimal alterations compared with groups 1 and 2. CONCLUSIONS: Costimulatory blockade and DST load can prevent the onset of chronic rejection in this experimental setting. Despite the wide availability of immunosuppressors, which makes transplantation a today's clinical routine, the solution to chronic rejection is still elusive. The synergistic role of splenocytes and costimulatory blockade raises interesting perspectives about the immunomodulatory role of spleen in tolerance induction.

[Epilepsy, cerebral calcifications and coeliac disease. The importance of an early diagnosis]. / Epilepsia, calcificaciones cerebrales y enfermedad celíaca. Importancia del diagnóstico precoz.

INTRODUCTION: Coeliac disease (CD) has been linked to several neurological disorders, with a clearly higher incidence of epilepsy than in the general population. Since Gobbi's original description of the epilepsy with cerebral calcifications and coeliac disease syndrome in 1992, various reports have been published concerning different stages of development, although a number of questions remain to be answered with respect to its pathogenesis. The aim of this study is to describe the clinical symptoms and progression of three patients with the characteristic syndrome, who were diagnosed in the early stages of the disease. CASE REPORTS: We describe the cases of three males, of school age, who visited because of partial seizures with visual symptoms that were secondarily generalised. A tomography scan of the head revealed bilateral occipital calcifications in all cases. The electroencephalogram showed temporooccipital paroxysmal discharges with a normal background rhythm. Tests for antiendomysium and antigliadin antibodies, with positive results, and a small intestine biopsy study were requested, which confirmed the suspicion of a grade 3 severe enteropathy. All the patients, following a gluten-free diet and taking anticonvulsants, were free of seizures in the follow-up (1, 2 and 8 years). CONCLUSIONS: It is of vital importance to investigate CD in any patient with epilepsy and occipital cerebral calcifications, even in the absence of digestive symptoms, since early diagnosis and treatment with exclusion of gluten affect how the syndrome courses later on.

Serum lamivudine levels in the presence of a lamivudine-resistant HBV mutant.

BACKGROUND/AIMS: Lamivudine efficiently inhibits hepatitis B virus replication and has been used to treat hepatitis B virus recurrence after orthotopic liver transplantation. Although effective, its use is hampered by viral breakthrough due to the appearance of hepatitis B virus drug-resistant strains. Aims of this work were to evaluate the inter- and intra-individual variations of lamivudine serum levels and the effects on the drug levels of the lamivudine-resistant hepatitis B virus mutant infection. METHODS: Serum lamivudine concentration was measured by high-performance liquid chromatography. Polymerase chain reaction analysis and sequencing analysis of the reverse transcriptase area of the polymerase was performed on each sample using specific primers. A polymerase chain reaction-enzyme-linked immunosorbent assay was used to differentiate between wild-type hepatitis B virus and lamivudine-resistant hepatitis B virus strain. RESULTS: Lamivudine serum levels presented minor inter- and intra-individual fluctuations along time, with an important increase at the time of the hepatitis flare-up due to the hepatitis B virus mutant presence. When the wild-type hepatitis B virus briefly reappeared as a mixed population, the titre of lamivudine dropped to below the detection level. CONCLUSIONS: While lamivudine serum levels appears stable when the anti-viral efficacy is fully achieved, important fluctuations are present according to the type of viral population, with a considerable decrease possibly due to the presence of the wild-type virus.

Residual strain effects on the stress field in a thick wall finite element model of the human carotid bifurcation.

A three-dimensional finite element model of the carotid artery bifurcation was constructed in order to determine the stress field and assess the modification of the stress field when residual strain is taken into account. Residual strain in the carotid bifurcation was characterized by experimental observations. According to these observations, a geometrical model of the carotid artery was constructed to exhibit a state free of strain. Appropriate boundary conditions were applied to yield the correct geometry in the unloaded state, and physiological levels of pressure and axial stretching were applied. The model took into account the varying thickness of the arterial wall along the bifurcation. For modeling purposes, the material was considered to be hyperelastic, incompressible, homogenous and isotropic. For comparison, a similar model of the carotid artery which does not include the effects of residual strain was also created. The results demonstrate that in the model of the carotid artery bifurcation with residual strain, the distribution of maximum principal stress along the inner wall and the circumferential stress throughout the wall is much more uniform than in the model without residual strain. The ratio between the stress at the inner and the outer walls is highest at the lateral wall of the carotid sinus; this is the same location known to be a site of low and oscillatory fluid wall shear stress, and the principal location of early intimal thickening. These results suggest that the localization of atherosclerosis in the carotid artery may be due to local variations in both fluid wall shear stress and solid wall stress.

The effects of time-varying curvature on velocity profiles in a model of the coronary arteries.

Blood flow patterns in the coronary arteries are of interest due to their possible involvement in atherosclerosis localization. Spatial variations in hemodynamic flow patterns are predominantly determined by the vessel geometry. The coronary arteries represent a unique situation in the cardiovascular system because their geometry undergoes large dynamic variations during each cardiac cycle due to the contraction of the heart. This study was initiated to analyze the effects of time-varying curvature on flow velocity profiles in a curved tube model of the coronary arteries. An in vitro flow model was constructed, which consisted of a flexible curved tube through which fluid flowed under a steady imposed pressure gradient. The radius of curvature of the tube was varied in time using a stepper motor and carriage. Two different deformation configurations were used to determine if variations in center of curvature displacement affected the velocity profiles. It was found in both cases that the skewing of the axial velocity profile depended on the instantaneous dynamic vessel movement, with maximal skewing occurring when the radius of curvature was in transition from the minimum to the maximum value. The change in skewing was greater for the case where carriage moved obliquely to the main direction of flow than when the carriage moved perpendicularly. Although this study was limited to relatively low values of the radius of curvature and change in curvature, an initial understanding of this flow situation was obtained which may lead to the development of more physiologic models.

Lateral deformation and movement effects on flow through distensible tube models of blood vessels.

The fluid flow through a tube with an oscillating elliptical cross-section was analyzed in order to understand better the effects of lateral deformation and movement on flow patterns in large and medium-sized blood vessels. Time-dependent elliptical deformation may be caused by external forces, as is the case for the large vessels near the heart, or by lateral movement of the entire compliant vessel, as in the coronary arteries. An analytic, perturbation-type solution was found for the case of fully developed flow in a tube where the cross-section oscillated periodically from an ellipse to a circle. Analytic expressions were found for all three components of the velocity vector. The effects of the deformation on the axial velocity profile included near-wall fluctuations in velocity that depended on the local wall motion. At higher values of the Womersley parameter, these effects were more pronounced. Secondary flow patterns were established that swirled fluid from the center of the vessel to the walls, then back to the center. It was concluded that these phenomena could be important to flow in the largest vessels, but may not be so important in determining flow patterns in the coronary arteries.

Fabricated hyalS micropatterns and surface guidance of NCTC 2544 continuous cell line: an in vitro study.

Surface topography is important in establishing tissue organisation adjacent to implants, smooth surfaces generally being associated with fibrous encapsulation. By virtue of its large hydrated molecular volume and its capacity to form molecular matrix, hyaluronic acid can expand the interfibrillar collagen spaces to allow the movement of cells, although it can also hamper their locomotion. Low molecular-weight hyaluronan can also stimulate cell proliferation, especially at low concentrations. The aim of the present work was to evaluate in vitro the growth and migratory behaviour of NCTC 2544 keratinocytes cultured on different materials microstructured with hyaluronic acid or sulfated hyaluronic acid to assess the possibility of using these devices in the repair process of soft tissues. Ultrastructural morphological analyses, morphometric evaluations and detection of cytoskeletal elements were performed. Our observations provide evidence that micrometer-size parallel grooves of hyaluronic acid can influence cell growth behaviour since cells seeded onto the microstructured substrate arranged themselves according to a shape and an orientation that clearly reflected the chemotropism exerted on them by the two forms of acid. These data also highlight the importance of accurate microtexture fabrication. We intend to follow up these in vitro studies with in vivo experimental applications using PET and gelatin substrates structured with HyalS to evaluate wound healing responses, and to extend our investigations of the cytoskeletal modifications induced by different microstructures.

Cervical intraepithelial neoplasia and human papillomavirus related lesions of the genital tract in HIV positive and negative women.

Two hundred and twenty one women at high risk for HIV (intravenous drug users and/or those with infected partners) were investigated, through a self-filled questionnaire and gynaecological examination, to define the relationship between genital Human Papilloma Virus (HPV) infections, preneoplastic cervical intraepithelial lesions (CIN) and behavioural risk factors. In the 121 HIV positive women, 58 (47%) had HPV lesions at colposcopic and/or cytologic examination and, out of these 58, 23 (40%) had CIN 1, CIN 2 or CIN 3. Six out of the 16 cases with CIN 1 and CIN 2 (37%) followed-up showed a rapid progression of the lesion to CIN 3; in 3 women the interval was 6 months, in the other 3 about 12 months. Only 5 (7%) of the remaining 66 women without HPV lesions had a CIN lesion, with an obviously significant difference on comparison with HPV positive subjects. Sixty two women out of the 121 (52%) had a previous diagnosis of condylomata. In the 100 HIV negative women, 23 (23%) had HPV lesions and, among these 23, 6 (26%) had CIN 1, CIN 2 or CIN 3; 1 of them had rapid progression from CIN 1 to CIN 3 within a year. Only 5 (3%) without HPV infection showed any kind of CIN. 33 women out of 100 (33%) had a previous clinical history of condylomata. Our findings strongly suggest that HIV infection is associated with HPV lesions and that cervical cytological abnormalities develop in this situation. There is a need for short interval cytological and colposcopic follow-up for women at high risk of HIV infection.

Heart rate variability and cardiorespiratory coupling in obstructive sleep apnea: elderly compared with young.

INTRODUCTION: Aging is known to be a major contributing factor to the increased risk of obstructive sleep apnea (OSA). With aging, breathing undergoes significant changes during sleep, increasing the prevalence of apnea events, which affects heart rate variability (HRV) and cardiorespiratory coupling (CRC). OBJECTIVES: To compare HRV and CRC during wakefulness and sleep between young and elderly patients with and without OSA; and to determine whether the presence of OSA in young and elderly patients has a different impact on HRV and CRC during sleep. METHODS: One hundred subjects, 50 young (mean age, 27 ± 9; 20 normal and 30 OSA) and 50 elderly (mean age, 65 ± 7; 20 normal and 30 OSA), underwent polysomnography. Spectral, cross-spectrum, and HRV parameters were analyzed during wakefulness and sleep. RESULTS: The spectral analysis indicated that age affected HRV, with higher values of low frequency (P < 0.05) in elderly subjects during wakefulness and an interaction between the presence of OSA and age. OSA influenced HRV during sleep with lower LF/HF ratios during stage 2 (S2) and rapid eye movement (REM) sleep (P <0.05), with an interaction between the presence of OSA and age in REM sleep. Elderly patients had significantly lower percent tachogram power coherent with respiration (%TPCR) during wakefulness (P < 0.05), and OSA led to lower %TPCR during S2. CONCLUSIONS: Age and OSA have an unfavorable impact on HRV, with reduced autonomic modulation during wakefulness, S2, and REM sleep. Age affects CRC during wakefulness and the presence of OSA affects CRC during sleep.

Peripheral blood serum markers for apoptosis and liver fibrosis: are they trustworthy indicators of liver realness?

BACKGROUND/AIMS: No reliable serum markers for liver inflammation, apoptosis and fibrosis have been established yet, although a large number have been evaluated. Moreover, it is not clear if a molecule detected and quantified in peripheral vein blood is a really trustworthy marker of the liver condition. To answer to this question, we had the opportunity to study paired serum samples drawn simultaneously during haemodynamic study from the right hepatic vein and from a peripheral vein from patients with hepatitis C virus related cirrhosis. METHODS: The serum levels of transforming growth factor beta-1, tumour necrosis factor-alpha, hyaluronic acid, soluble (s)human leukocyte class I antigens, soluble FAS ligand, and stumour necrosis factor related ligand were assessed in a consecutive series of 15 patients with hepatitis C virus related cirrhosis. RESULTS: No statistically significant differences were found between hepatic vein and peripheral vein levels for the cytokines, substance or soluble molecules evaluated, excepted for shuman leukocyte class I antigens. Instead a strong correlation between hepatic vein and peripheral vein levels was present for: hepatic vein, shuman leukocyte class I antigens, tumour necrosis factor-alpha, soluble FAS ligand and stumour necrosis factor related ligand, but not for transforming growth factor beta-1. CONCLUSIONS: Our results show that peripheral vein measurements seem to reflect the liver compartment in a large majority of cases, but not for all molecules and probably for any liver diseases. Further studies on this line are warranted in particular for new molecules.

Soluble apoptosis molecules in primary biliary cirrhosis: analysis and commitment of the Fas and tumour necrosis factor-related apoptosis-inducing ligand systems in comparison with chronic hepatitis C.

Apoptosis in the liver is generated mainly by the Fas system. Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) has been proposed recently as a new apoptotic inducer. In the liver environment hepatocytes and biliary epithelial cells express TRAIL receptors which are up-regulated by increased levels of bile acids and during viral hepatitis. As for FasL, a soluble form of TRAIL has been described. To explore the commitment and level of activation of these two apoptotic systems in patients affected by primary biliary cirrhosis (PBC) or chronic hepatitis C (CH-C), a comparative study was drawn. Thirty patients with PBC on ursodeoxycholic acid have been enrolled. This group was compared with 30 patients with CH-C and with 20 healthy subjects. Soluble Fas ligand (sFasL) and soluble TRAIL (sTRAIL) levels were evaluated by double determinant immune assay and enzyme-linked immunosorbent assay (ELISA), respectively. Soluble FasL molecules were higher in PBC compared to CH-C (P=0 x 009). Soluble FasL was not detected in controls. Soluble TRAIL was significantly higher in CH-C patients compared to PBC (P=0 x 0001). Soluble TRAIL levels were higher in PBC and in CH-C than in controls (P=0 x 015 and P<0 x 001, respectively). No correlation between sFasL and sTRAIL, stage of disease, liver histology in each disease and cytolysis was present. Our data show different levels of commitment of TRAIL and Fas apoptosis-inducing systems in CH-C and PBC. Thus a different prominent role of TRAIL and Fas systems in the pathogenesis of these two conditions can be speculated: the former by inducing the death of infected hepatocytes, the latter by mediating the disappearance of bile duct.

Pre-oxygenation in the obese patient: effects of position on tolerance to apnoea.

BACKGROUND: In obese patients, reduced functional residual capacity exacerbated by supine position might decrease the effectiveness of pre-oxygenation and the tolerance to apnoea. The aim of this study was to compare the effect of body posture during pre-oxygenation, sitting or supine, on its effectiveness in obese patients. METHODS: Forty obese patients (BMI > or =35 kg m(-2)) undergoing surgery with general anaesthesia were randomly assigned to one of two groups: Group 1 (sitting, n=20) or Group 2 (supine, n=20). In the predetermined body position, pre-oxygenation was achieved with eight deep breaths within 60 s and an oxygen flow of 10 litre min(-1). After rapid sequence induction of anaesthesia in decubitus position, the trachea was intubated and the patient was left apneic and disconnected from the anaesthesia circuit until Sp(o2) decreased to 90%. The time taken for desaturation to 90% from the end of induction of anaesthesia was recorded. Arterial blood oxygen tension was measured before (baseline) and after pre-oxygenation. Values were compared with two-way anova and unpaired Student's t-test. RESULTS: Oxygen and carbon dioxide tensions were similar between groups, both at baseline and after pre-oxygenation. However, the mean time to desaturation to 90% was significantly longer in the sitting group compared with the supine group [mean (SD): 214 (28) vs 162 (38) s, P<0.05]. CONCLUSIONS: Pre-oxygenation in sitting position significantly extends the tolerance to apnoea in obese patients when compared with the supine position.