CineCT platform for in vivo and ex vivo measurement of 3D high resolution Lagrangian strains in the left ventricle following myocardial infarction and intramyocardial delivery of theranostic hydrogel.

Myocardial infarction (MI) produces acute changes in strain and stiffness within the infarct that can affect remote areas of the left ventricle (LV) and drive pathological remodeling. We hypothesized that intramyocardial delivery of a hydrogel within the MI region would lower wall stress and reduce adverse remodeling in Yorkshire pigs (n = 5). 99mTc-Tetrofosmin SPECT imaging defined the location and geometry of induced MI and border regions in pigs, and in vivo and ex vivo contrast cine computed tomography (cineCT) quantified deformations of the LV myocardium. Serial in vivo cineCT imaging provided data in hearts from control pigs (n = 3) and data from pigs (n = 5) under baseline conditions before MI induction, post-MI day 3, post-MI day 7, and one hour after intramyocardial delivery of a hyaluronic acid (HA)-based hydrogel with shear-thinning and self-healing properties to the central infarct area. Isolated, excised hearts underwent similar cineCT imaging using an ex vivo perfused heart preparation with cyclic LV pressurization. Deformations were evaluated using nonlinear image registration of cineCT volumes between end-diastole (ED) and end-systole (ES), and 3D Lagrangian strains were calculated from the displacement gradients. Post-MI day 3, radial, circumferential, maximum principal, and shear strains were reduced within the MI region (p < 0.04) but were unchanged in normal regions (p > 0.6), and LV end diastolic volume (LV EDV) increased (p = 0.004), while ejection fraction (EF) and stroke volume (SV) decreased (p < 0.02). Post-MI day 7, radial strains in MI border zones increased (p = 0.04) and dilation of LV EDV continued (p = 0.052). There was a significant negative linear correlation between regional radial and maximum principal/shear strains and percent infarcted tissue in all hearts (R2 > 0.47, p < 0.004), indicating that cineCT strain measures could predict MI location and degree of injury. Post-hydrogel day 7 post-MI, LV EDV was significantly reduced (p = 0.009), EF increased (p = 0.048), and radial (p = 0.021), maximum principal (p = 0.051), and shear strain (p = 0.047) increased within regions bordering the infarct. A smaller strain improvement within the infarct and normal regions was also noted on average along with an improvement in SV in 4 out of 5 hearts. CineCT provides a reliable method to assess regional changes in strains post-MI and the therapeutic effects of intramyocardial hydrogel delivery.

Protocolised thromboelastometric-guided haemostatic management in patients with traumatic brain injury: a pilot study.

Coagulopathy in patients with traumatic brain injury is associated with an increase in morbidity and mortality. Although timely and aggressive treatment of coagulopathy is of paramount importance, excessive transfusion of blood products has been linked with poor long-term outcomes in patients with traumatic brain injury. A point-of-care thromboelastometric-guided algorithm could assist in creating a more individually tailored approach to each patient. The aim of this study was to evaluate the feasibility of implementing a thromboelastometric-guided algorithm in centres that were formerly naïve to thromboelastometry. Hence, we developed such an algorithm and provided training to four centres across Europe to direct the haemostatic management of patients with severe traumatic brain injury. The primary outcome was adherence to the algorithm and timing of the availability of relevant results. Thirty-two patients were included in the study. Complete adherence to the algorithm was observed in 20 out of 32 cases. The availability of thromboelastometric results after hospital admission was reported significantly earlier than conventional coagulation tests (median (IQR [range]) 33 (20-40 [14-250]) min vs. 71 (51-101 [32-290]) min; p = 0.037). Although only 5 out of 32 patients had abnormalities of conventional coagulation tests, 21 out of 32 patients had a coagulopathic baseline thromboelastometric trace. Implementing a thromboelastometric-guided algorithm for the haemostatic therapy of traumatic brain injury is feasible in centres formerly naïve to this technology and may lead to more rapid and precise coagulation management. Further large-scale studies are warranted to confirm the results of this pilot trial and evaluate clinical outcomes.

Post-operative pain relief using local infiltration analgesia during open abdominal hysterectomy: a randomized, double-blind study.

BACKGROUND: Post-operative pain is common and often severe after open abdominal hysterectomy, and analgesic consumption high. This study assessed the efficacy of local infiltration analgesia (LIA) injected systematically into different tissues during surgery compared with saline on post-operative pain and analgesia. METHODS: Fifty-nine patients were randomized to Group LIA (n = 29) consisting of 156 ml of a mixture of 0.2% ropivacaine + 30 mg ketorolac + 0.5 mg (5 ml) adrenaline, where the drugs were injected systematically in the operating site, around the proximal vagina, the ligaments, in the fascia and subcutaneously, or to saline and intravenous ketorolac, Group C (Control, n = 28), in a double-blind study. Post-operative pain, analgesic consumption, side-effects, and home discharge were analysed. RESULTS: Median dose of rescue morphine given 0-24 h after surgery was significantly lower in group LIA (18 mg, IQR 5-25 mg) compared with group C (27 mg, IQR 15-43 mg, P = 0.028). Median time to first analgesic injection was significantly longer in group LIA (40 min, IQR 20-60 min) compared with group C (20 min, IQR 12-30 min, P = 0.009). NRS score was lower in the group LIA compared with group C in the direct post-operative period (0-2 h). No differences were found in post-operative side-effects or home discharge between the groups. DISCUSSION: Systematically injected local infiltration analgesia for pain management was superior to saline in the primary endpoint, resulting in significantly lower rescue morphine requirements during 0-24 h, longer time to first analgesic request and lower early post-operative pain intensity.

Ultrasonography-guided radial artery catheterization is superior compared with the traditional palpation technique: a prospective, randomized, blinded, crossover study.

BACKGROUND: Radial artery catheterization is gaining popularity for diagnostic and interventional procedures. Palpation technique is widely used for the procedure, but ultrasonography has been shown to increase catheterization success. A recently described ultrasonography technique is termed 'dynamic needle tip positioning'. We aimed to compare the traditional palpation technique and dynamic needle tip positioning technique in regard to clinically relevant end points. METHODS: The study was conducted as a randomized, patient-blinded, crossover study. Patients underwent bilateral radial artery catheterization using both techniques. The primary end point of the study was needle manipulation time. Additional end points were (1) the number of skin perforations, (2) the number of attempts targeting the vessel, (3) the number of catheters placed in first attempt and (4) the number of catheters used. RESULTS: Forty patients were analyzed. There was no significant difference in median needle manipulation time [32 s (range 11-96 s) vs. 39 s (range 9-575 s), P = 0.525], although the variance was lower in the dynamic needle tip positioning group (P < 0.001). In the traditional palpation technique group, a higher number of skin perforations (57 vs. 40, P = 0.003), catheters (46 vs. 40, P = 0.025) and attempts targeting the vessel (104 vs. 43, P < 0.001) were necessary compared with the ultrasonography dynamic needle tip positioning group. First attempt success rate was significantly higher in the ultrasonography dynamic needle tip positioning group (23/40 vs. 38/40, P < 0.001). CONCLUSION: Ultrasonography guidance using the dynamic needle tip positioning technique for radial artery catheterization significantly improves clinically relevant aspects of the procedure.

Public health response to an outbreak of Legionnaires' disease in Edinburgh, United Kingdom, June 2012.

We report an outbreak comprising 50 confirmed cases of Legionnaires' disease in Edinburgh, Scotland, June 2012. In addition, there were 49 suspected cases. Epidemiological evidence suggests that a common outdoor airborne exposure occurred over south-west Edinburgh. This probably emanated from cooling towers in the north-east of the affected area, although not yet clearly linked by scientific evidence. The co-ordinated public health, environmental and clinical response helped prevent ongoing exposure and mitigated associated mortality and morbidity.

High-resolution solid-state manometry of the effect of rocuronium on barrierpressure.

BACKGROUND: The pressure in the lower esophageal sphincter (LES) is partly dependent on striated muscles derived from the crural portion of the diaphragm. The effect of neuromuscular blockade on the integrity of the esophagogastric junction is not well studied. We conducted a prospective interventional study to determine the effect of rocuronium on the barrier pressure (LES pressure - intragastric pressure) of the esophagogastric junction. We also studied the effect of positive pressure ventilation on the barrier pressure after neuromuscular blockade with rocuronium. METHODS: Fourteen patients classified as American Society of Anesthesiologists classification system (ASA) I or II (aged 18-75 years) who presented for elective surgery (11 cholecystectomy, 3 inguinal hernia) participated in the study. Esophageal manometry was performed during anesthetization with propofol, fentanyl, and sevoflurane. The LES pressure was studied prior to anesthesia, after anesthesia induction during spontaneous breathing with laryngeal mask airway, after administration of rocuronium (0.6 mg/kg), and during positive pressure ventilation. RESULTS: Muscle relaxation with rocuronium showed no significant changes in barrier pressure when comparing the pressure immediately before rocuronium administration with the pressure obtained after rocuronium administration at the time point of 0% train-of-four (TOF). Conversion to positive pressure ventilation did not change the barrier pressure with inspiration or expiration. The greatest decrease in barrier pressure was measured after inducing anesthesia when comparing pressures during inspiration (P < 0.01). CONCLUSIONS: Neuromuscular blockade with rocuronium and conversion from spontaneous breathing to positive pressure ventilation does not decrease the barrier pressure during anesthesia induction.

Effects of cricoid pressure and remifentanil on the esophageal sphincters using high-resolution solid-state manometry.

BACKGROUND: Cricoid pressure has been shown to decrease the pressure in the lower esophageal sphincter (LES), increasing the risk of aspiration. Whether this reaction is due to pain associated with the application of cricoid pressure has not been studied. The aim of this study was to compare the effects of cricoid pressure with those of peripheral pain on pressures in the LES, and to study whether remifentanil influences these effects. Data from the upper esophageal sphincter (UES) are also described. METHODS: Continuous solid-state manometry was performed in 14 healthy volunteers. Initially, the effect of remifentanil (target-controlled infusion with a plasma target concentration of 5.0 ng/ml) was studied, and thereafter, the effects of cricoid pressure and peripheral pain stimulation (cold stimulation). Finally, these two interventions were repeated under ongoing remifentanil infusion. RESULTS: Remifentanil decreased the LES pressure significantly [ΔP-6.5 mmHg, 95% confidence interval (95% CI) -1.7 to -11.2]. Cricoid pressure application decreased the LES pressure significantly (ΔP-3.7 mmHg, 95% CI -1.4 to 6.1), whereas peripheral pain did not (ΔP 1.2 mmHg, 95% CI -3.5 to 1.1). Under ongoing remifentanil infusion, no cricoid pressure-induced LES relaxation was observed. Cricoid pressure induced high pressures in the area of the UES, 215.7 (±91.2) mmHg without remifentanil vs. 219.4 (±74.2) mmHg with remifentanil. CONCLUSIONS: Remifentanil as well as cricoid pressure per se induced decreases in LES pressure. However, cricoid pressure-induced changes of the barrier pressure were not significant whether induced with or without an infusion of remifentanil.

Kinetic model-based factor analysis of dynamic sequences for 82-rubidium cardiac positron emission tomography.

PURPOSE: Factor analysis has been pursued as a means to decompose dynamic cardiac PET images into different tissue types based on their unique temporal signatures to improve quantification of physiological function. In this work, the authors present a novel kinetic model-based (MB) method that includes physiological models of factor relationships within the decomposition process. The physiological accuracy of MB decomposed (82)Rb cardiac PET images is evaluated using simulated and experimental data. Precision of myocardial blood flow (MBF) measurement is also evaluated. METHODS: A gamma-variate model was used to describe the transport of (82)Rb in arterial blood from the right to left ventricle, and a one-compartment model to describe the exchange between blood and myocardium. Simulations of canine and rat heart imaging were performed to evaluate parameter estimation errors. Arterial blood sampling in rats and (11)CO blood pool imaging in dogs were used to evaluate factor and structure accuracy. Variable infusion duration studies in canine were used to evaluate MB structure and global MBF reproducibility. All results were compared to a previously published minimal structure overlap (MSO) method. RESULTS: Canine heart simulations demonstrated that MB has lower root-mean-square error (RMSE) than MSO for both factor (0.2% vs 0.5%, p < 0.001 MB vs MSO, respectively) and structure (3.0% vs 4.7%, p < 0.001) estimations, as with rat heart simulations (factors: 0.2% vs 0.9%, p < 0.001 and structures: 3.0% vs 6.7%, p < 0.001). MB blood factors compared to arterial blood samples in rats had lower RMSE than MSO (1.6% vs 2.2%, p =0.025). There was no difference in the RMSE of blood structures compared to a (11)CO blood pool image in dogs (8.5% vs 8.8%, p =0.23). Myocardial structures were more reproducible with MB than with MSO (RMSE=3.9% vs 6.2%, p < 0.001), as were blood structures (RMSE=4.9% vs 5.6%, p =0.006). Finally, MBF values tended to be more reproducible with MB compared to MSO (CV= 10% vs 18%, p =0.16). The execution time of MB was, on average, 2.4 times shorter than MSO (p < 0.001) due to fewer free parameters. CONCLUSIONS: Kinetic model-based factor analysis can be used to provide physiologically accurate decomposition of (82)Rb dynamic PET images, and may improve the precision of MBF quantification.

Body positions and esophageal sphincter pressures in obese patients during anesthesia.

BACKGROUND: The lower esophageal sphincter (LES) and the upper esophageal sphincter (UES) play a central role in preventing regurgitation and aspiration. The aim of the present study was to evaluate the UES, LES and barrier pressures (BP) in obese patients before and during anesthesia in different body positions. METHODS: Using high-resolution solid-state manometry, we studied 17 patients (27-63 years) with a BMI>or=35 kg/m(2) who were undergoing a laparoscopic bariatric surgery before and after anesthesia induction. Before anesthesia, the subjects were placed in the supine position, in the reverse Trendelenburg position (+20 degrees) and in the Trendelenburg position (-20 degrees). Thereafter, anesthesia was induced with remifentanil and propofol and maintained with remifentanil and sevoflurane, and the recordings in the different positions were repeated. RESULTS: Before anesthesia, there were no differences in UES pressure in the different positions but compared with the other positions, it increased during the reverse Trendelenburg during anesthesia. LES pressure decreased in all body positions during anesthesia. The LES pressure increased during the Trendelenburg position before but not during anesthesia. The BP remained positive in all body positions both before and during anesthesia. CONCLUSION: LES pressure increased during the Trendelenburg position before anesthesia. This effect was abolished during anesthesia. LES and BPs decreased during anesthesia but remained positive in all patients regardless of the body position.

Effects of different respiratory maneuvers on esophageal sphincters in obese patients before and during anesthesia.

BACKGROUND: Data on esophageal sphincters in obese individuals during anesthesia are sparse. The aim of the present study was to evaluate the effects of different respiratory maneuvers on the pressures in the esophagus and esophageal sphincters before and during anesthesia in obese patients. METHODS: Seventeen patients, aged 28-68 years, with a BMI ≥ 35 kg/m², who were undergoing a laparoscopic gastric by-pass surgery, were studied, and pressures from the hypopharynx to the stomach were recorded using high-resolution solid-state manometry. Before anesthesia, recordings were performed during normal spontaneous breathing, Valsalva and forced inspiration. The effects of anesthesia induction with remifentanil and propofol were evaluated, and positive end-expiratory pressure (PEEP) 10 cmH2O was applied during anesthesia. RESULTS: During spontaneous breathing, the lower esophageal sphincter (LES) pressure was significantly lower during end-expiration compared with end-inspiration (28.5 ± 7.7 vs. 35.4 ± 10.8 mmHg, P<0.01), but barrier pressure (BrP) and intra-gastric pressure (IGP) were unchanged. LES, BrP (P<0.05) and IGP (P<0.01) decreased significantly during anesthesia. BrP remained positive in all patients. IGP increased during Valsalva (P<0.01) but was unaffected by PEEP. Esophageal pressures were positive during both spontaneous breathing and mechanical ventilation. Esophageal pressures increased during PEEP from 9.4 ± 3.8 to 11.3 ± 3.3 mmHg (P<0.01). CONCLUSION: During spontaneous breathing, the LES pressure was the lowest during end-expiration but there were no differences in BrP and IGP. LES, BrP and IGP decreased during anesthesia but BrP remained positive in all patients. During the application of PEEP, esophageal pressures increased and this may have a protective effect against regurgitation.

Work related perceived stress and muscle activity during standardized computer work among female computer users.

The current study investigated the associations between work-related perceived stress and surface electromyographic (sEMG) parameters (muscle activity and muscle rest) during standardized simulated computer work (typing, editing, precision, and Stroop tasks). It was part of the European case-control study, NEW (Neuromuscular assessment in the Elderly Worker). The present cross-sectional study was based on a questionnaire survey and sEMG measurements among Danish and Swedish female computer users aged 45 or older (n=49). The results show associations between work-related perceived stress and trapezius muscle activity and rest during standardized simulated computer work, and provide partial empirical support for the hypothesized pathway of stress induced muscle activity in the association between an adverse psychosocial work environment and musculoskeletal symptoms in the neck and shoulder.

Effects of pain stimulation on bispectral index, heart rate and blood pressure at different minimal alveolar concentration values of sevoflurane.

BACKGROUND: The aim of the present study was to examine the level of unconsciousness measured with bispectral index (BIS) at different minimal alveolar concentration (MAC) levels of sevoflurane, and to study the hemodynamic and BIS reactions during noxious stimulation with transcutaneous electrical nerve stimulation (TENS) and an ice water pain test (IWP). METHODS: This study was approved by the Ethics Committee and was performed on 10 healthy, young volunteers (six males and four females), ASA physical status I. Anesthesia was induced and maintained with sevoflurane in an oxygen/air mixture. The volunteers were spontaneously breathing, but if necessary, ventilation was mechanically supported. TENS and IWP were performed at 1.0, 1.5 and 2.0 MAC of sevoflurane. RESULTS: At 1.0 MAC, there was a significant increase in BIS during pain stimulation both with IWP (P<0.03) and with TENS (P<0.005), but at 1.5 MAC there were no changes. A marked variation in BIS was seen at 2.0 MAC, with periods of burst suppression and periods of high BIS values despite clinical signs of deep anesthesia. These marked variations in BIS were seen before, during and after pain stimulation. One volunteer (# 8) had a short episode of convulsions at 2.0 MAC. CONCLUSION: BIS, heart rate and blood pressure increased during pain stimulation at 1.0 MAC but not at 1.5 MAC of sevoflurane. There was a remarkable variation in BIS at 2.0 MAC of sevoflurane, with BIS values indicating wakefulness despite clinical signs of deep anesthesia. This BIS variation is probably caused by epileptogenic activity due to sevoflurane.

Effects of fentanyl on gastric myoelectrical activity: a possible association with polymorphisms of the mu-opioid receptor gene?

BACKGROUND: Opioids have inhibitory effects on gastric motility, but the mechanism is far from clear. Electrical slow waves in the stomach determine the frequency and the peristaltic nature of gastric contractions. The primary aim of this study was to investigate the effects of the opioid fentanyl on gastric myoelectric activity. As there were large variations between the subjects, we investigated whether the variation was correlated to single nucleotide polymorphisms (SNP) of the mu-opioid receptor (MOR) gene. METHODS: We used cutaneous multichannel electrogastrography (EGG) to study myoelectrical activity in 20 patients scheduled for elective surgery. Fasting EGG was recorded for 30 min, followed by intravenous administration of fentanyl 1 microg/kg and subsequent EGG recording for 30 min. Spectral analysis of the two recording periods was performed and the variables assessed were dominant frequency (DF) of the EGG and its power (DP). Genetic analysis of the SNP A118G and G691C of the MOR gene was performed with the polymerase chain reaction technique. RESULTS: There was a significant reduction in DF and DP after intravenous fentanyl. However, there was a large variation between the patients. In eight subjects EGG was unaffected, five subjects had a slower DF (bradygastria) and in six subjects the slow waves disappeared. We found no correlation between the EGG outcome and the presence of A118G or G691C in the MOR gene. CONCLUSIONS: Fentanyl inhibited gastric myoelectrical activity in about half of the subjects. The variation could not be explained by SNP in the MOR gene. Because of small sample size, the results must be regarded as preliminary observations.

Trapezius muscle rest time during standardised computer work--a comparison of female computer users with and without self-reported neck/shoulder complaints.

Work related musculoskeletal disorders (WMSDs) in the shoulder/neck area are a common and increasing problem among European computer workers, especially women. Long-term low-level workloads with low degree of muscle rest are a potential risk factor for developing WMSDs. The purpose of the present study of female computer users (age 45-65 years) in Denmark and Sweden was to investigate if subjects with self-reported neck/shoulder complaints (cases, N=35) show less trapezius muscle relative rest time (RRT) than controls (N=44) when performing standardised short-term computer work tasks in controlled laboratory conditions. Surface electromyography (EMG) signals were recorded bilaterally from the upper trapezius muscles during a type, edit, precision and colour word stress task. Besides RRT, 10th percentile RMS values were calculated. On the average, 15 of the cases and 18 of the controls showed analysable EMG files per task. For the colour word stress task, the results showed lower RRT values and higher 10th percentile RMS amplitude levels among cases compared to controls. No such signs could be found for the other tasks performed. The present results indicate an increased motor response to a psychological stressor among subjects with self-reported neck/shoulder complaints.

Effect of estrogen on leptin and expression of leptin receptor transcripts in prepubertal dairy heifers.

Plasma leptin concentrations increase as growing dairy heifers approach puberty and have greater plasma estrogen. In intact and ovariectomized rodents, estrogen has been shown to modulate expression of leptin and its receptor (Ob-R). To determine if estrogen regulates the bovine leptin system, prepubertal dairy heifers were ovariectomized at 140 d of age or left intact. A month later, both groups received a subcutaneous injection of excipient or 17beta-estradiol for 3 consecutive days. Neither ovarian status nor 17beta-estradiol injection altered plasma leptin or leptin mRNA abundance in adipose tissue depots. To assess whether these factors affected Ob-R expression, we tested 20 bovine tissues for leptin receptor (Ob-R) by using quantitative real-time PCR assays for the short receptor isoform (Ob-Ra), the long receptor isoform (Ob-Rb), and all receptor isoforms (Ob-R(TOTAL)). Ob-R(TOTAL) was detected in all tissues, with copy numbers covering 3 orders of magnitude between the lowest and highest expressing tissues (kidney cortex vs. liver). The Ob-Rb isoform accounted for 40% of Ob-R(TOTAL) in the hypothalamus, but averaged less than 3% of Ob-R(TOTAL) in peripheral tissues. Reciprocally, Ob-Ra accounted for only 19% of Ob-R(TOTAL) in the hypothalamus and for nearly all of Ob-R(TOTAL) in most peripheral tissues. Finally, we evaluated the effects of ovarian status and 17beta-estradiol on Ob-R expression in selected tissues. Treatment with 17beta-estradiol reduced Ob-R(TOTAL), Ob-Rb, and Ob-Ra expression by 70% in the uterine endometrium and tended to do the same in mammary adipose tissue. There was no effect of 17beta-estradiol on Ob-R in the hypothalamus, liver, soleus muscle, or subcutaneous adipose tissue. We conclude that greater estrogen secretion does not cause increased plasma leptin in prepubertal dairy heifers but estradiol can modulate Ob-R expression in some estrogen-responsive tissues.

[Delays of treatment of acute myocardial infarction with ST elevation admitted to the CCU (coronary care unit) in Alsace]. / Délais de prise en charge de l'infarctus aigu du myocarde avec sus-décalage persistant du segment ST admis dans les USIC d'Alsace.

OBJECTIVE: to determine the time delay from symptom onset to diagnosis and treatment of patients with persistant ST segment elevation myocardial infarction (STEMI). DESIGN: prospective observational study. METHOD: patients with symptoms onset < 24 h admitted in all 10 cardiac intensive care units in one French administrative region (Alsace). Data were recorded by doctors on duty soon after hospital admission. Patients with STEMI during hospital stay or as a complication of cardiac interventional procedure were excluded. The Kruskal-Wallis test was used to assess statistical differences between the groups (p value < 0.05). RESULT: from April to October 2004, 326 patients were admitted for STEMI. Median time between the symptoms onset and the patient's call for medical help was 60 minutes. General practitioners were the first medical contact in 41%. The time from symptoms onset to first medical intervention and from first medical intervention to coronary care unit admission were markedly shorter in patients who had directly called the Emergency Medical Services (group 15-110 patients i.e. 33% of the study population): 44 min vs 75 min otherwise (p=0,003). Median transport time was 60 min. Sixty two percent of the pts were transported by the Emergency Medical Services. The median time from symptoms onset to initiation of reperfusion therapy was 240 min. It was significantly lower in group 15 (170 min vs 286 min - p < 0,001) and for thrombolytic therapy (190 min versus 245 min for primary angioplasty, p=0,007). When thrombolysis (THL) was used, 89% of the pts could be treated during 6 hours of symptoms onset and 44% in 3 hours. For angioplasty only 4% of the pts were treated in the first 90 minutes, 9% in the 2 hours and 30% in the 3 hours of symptoms onset. If the time delay is evaluated from the 1 st medical intervention, call to reperfusion intervention was significatly shorter for THL: 91 versus 157 min, p< 0,003. Angioplasty represented 75% of reperfusion strategy in our area and THL alone only 2,7% and combine therapy 5,4%. CONCLUSION: our study documents the beneficial effect of a direct call to Emergency Medical Services. Our results also underscore the need for an effort to reduce the time to offer the best appropriate reperfusion techniques in STEMI pts: speed up the admission in the cath-lab, think about pre-hospital thrombolysis followed by coronary angioplasty if necessary.

Leptin does not act directly on mammary epithelial cells in prepubertal dairy heifers.

The mammary gland of prepubertal dairy heifers consists of parenchyma expanding into the stroma, a matrix of connective and adipose tissue. High planes of nutrition increase stromal mass, but inhibit growth of parenchyma. The parenchyma consists of epithelial cells proliferating in response to growth factors such as insulin like growth factor-I (IGF-I). These observations have led to the hypothesis that elevated planes of nutrition increase leptin production, which in turn inhibits IGF-I-mediated epithelial cell proliferation. To assess this possibility, heifers were offered planes of nutrition sustaining average daily gains of 715 g/d (normal; NP) or 1,202 g/d (high; HP) from 42 d of age until slaughter at 240 kg. At slaughter, HP heifers had 2-fold greater plasma leptin concentration and 3-fold greater leptin mRNA abundance in mammary stroma and parenchyma. To assess the causal nature between leptin and parenchymal development, the induction of signaling events and functional responses in the MAC-T cell line and in primary mammary epithelial cells by leptin was examined. Leptin did not induce phosphorylation of signal transducers and activators of transcription (STAT)3, STAT5, extracellular signal-regulated kinase (ERK1/2), or AKT/Protein kinase B. Consistent with its inability to signal, leptin did not alter basal- or IGF-I-stimulated thymidine incorporation or increase suppressors of cytokine signaling 3 (SOCS3) expression in these cells. Transcripts corresponding to the short leptin receptor form were present in mammary tissue, but those corresponding to the long signaling form were not detected in either mammary tissue or cells. In conclusion, elevated planes of nutrition increase leptin synthesis in mammary stroma, but leptin does not act directly on bovine mammary epithelial cells.

Stimulus intensity and the comparative efficacy of mu- and kappa-opioid agonists on nociceptive spinal reflexes in the rat.

The influence of stimulus intensity was tested on the relative spinal efficacy of intravenously administered mu- (fentanyl) and kappa-opioid (U-50,488) agonists. Spinal reflexes were generated by different intensities of noxious electrical stimuli in alpha-chloralose anaesthetized, spinalized rats. Both drugs became less effective as the intensity of C-fibre generated responses was increased, but U-50,488 retained the ability to reduce responses to the same degree as fentanyl. The effects were naloxone reversible. The results indicate that kappa-opioid receptor activation has similar potential for spinal analgesia as does activation of mu-opioid receptors.

Medical evidence concerning the suitability to succeed to the tenancy of a farm: the case of 'toad of toad hall'.

A hill farmer applied to succeed to the tenancy of his farm on the death of his mother who had leased the farm from his maternal aunt. As landlord, she opposed the application which was heard at an Agricultural Land Tribunal (ALT) convened under the provisions of the Agricultural Holdings Act, 1986. The ALT is a court of first instance. The applicant had to prove his eligibility and his suitability. His eligibility was not disputed. Both parties called medical evidence having a bearing on his physical health which was a matter relevant to the issue of suitability. It was in question because there were allegations of excessive drinking and alcohol-related offending. Finding no evidence that the applicant's drinking affected his farming ability, the Tribunal found in his favour and his application to succeed to the tenancy was granted.