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Audrey Giocanti-Aurégan,1 Alfredo García-Layana,2 Tunde Peto,3 Brittany Gentile,4 Gloria C Chi,4 Mirela Mirt,5 Charlotte E Kosmas,6 Jeremy Lambert,7 Sally Lanar,7 Hannah B Lewis,6 Nancy M Holekamp8 1Ophthalmology Department, Avicenne Hospital, Bobigny, France; 2Clínica Universidad de Navarra, University of Navarra, Pamplona, 31009, Spain; 3Queen’s University Belfast, Belfast, UK; 4Genentech, South San Francisco, CA, USA; 5F. Hoffmann-La Roche, Basel, Switzerland; 6Patient Centred Outcomes, ICON Plc, Reading, UK; 7Patient Centred Outcomes, ICON Plc, Lyon, France; 8Pepose Vision Institute, Chesterfield, MO, USACorrespondence: Audrey Giocanti-Aurégan, Ophthalmology Department, Avicenne hospital, 125 Rue de Stalingrad, Bobigny Cedex, 93009, France, Tel +33 14 895 5815, Fax +33 14 895 5212, Email audrey.giocanti@aphp.frPurpose: Neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME) patients treated with intravitreally injected anti-vascular endothelial growth factor (anti-VEGF) monotherapies achieve lower vision improvements compared with patients in clinical trials. This qualitative research study aimed to better understand the real-world anti-VEGF treatment experience from nAMD and DME patients’, caregivers’, and retina specialists’ perspectives.Methods: One-time, semi-structured, individual interviews were conducted with adult patients with nAMD or DME treated with anti-VEGF injections for ≥ 12 months, their caregivers, and experienced retina specialists. Interview transcripts were analyzed qualitatively using a thematic analysis approach.Results: A total of 49 nAMD and 46 DME patients, 47 nAMD and 33 DME caregivers, and 62 retina specialists were interviewed in the USA, Canada, France, Germany, Italy and Spain. Most (79%) patients and caregivers reported disruptions to their routine on the day before, the day of, or the day after anti-VEGF injection. Seven nAMD patients (14%) and 14 DME patients (30%) reported having missed an injection visit. The most frequently reported driver for adherence for patients was the doctor–patient relationship (n=66, 70%), whereas for caregivers, it was the ease of booking an appointment (n=25, 32%). Retina specialists reported patient education on the treatment (n=28, 45%) as the most important driver. Treatment barriers could be grouped into four categories: tolerability, clinical factors, logistical parameters and human factors. The most frequently reported barrier to adherence for patients and caregivers was related to side effects (pain/discomfort/irritation: n=63, 67% of patients; n=52, 66% of caregivers), whereas for retina specialists it was logistical parameters (travel logistics: n=44, 71%).Conclusion: This study highlights the importance of the doctor–patient relationship and patient education as key drivers, and treatment tolerability and logistics as key barriers to treatment adherence. Improved doctor–patient relationship/communication and patient education together with new therapies offering convenience, long-acting effectiveness, and better tolerability may improve treatment adherence.Keywords: qualitative interviews, treatment experience, adherence, neovascular age-related macular degeneration, diabetic macular edema

Due to superior mechanical and metallurgical performance, Nickel-base Alloys 617 and 276 have been considered as structural material for used in complex and stochastic applications. Surface irregularities such as cracks in the material may be vulnerable to the structural integrity of an engineering component. Void growth behavior is however analyzed using crystal plasticity theory in nickel-based super alloys. Elastic-plastic fracture mechanics base single compact tension specimen has been used to determine the J1C value as a function of temperature of austenitic Alloy 617 and 276 for ductile crack growth behavior. Crack formation is appropriately explained through crack nucleation based on the microstructural heterogeneity properties of the alloys. Alloy 617 showed a fair increased resistance to fracture as temperature increased from ambient to 5000C for duplicate testing, satisfying the EPFM criteria. Whereas the J1C values of Alloy 276 increased gradually with temperature up to 300° C and due to enhanced plasticity in the vicinity of 4000 C this alloy shows inconsistent value. Two-dimensional simulation of J-integral model of these nickel base super alloys at temperature range 1000C to 5000 C has been proposed. Particular focus is given on the load line displacement where crack propagation occurs during the loading phase only. Path independency of J-integral has been clearly demonstrated for both the alloys up to 3000 C employing finite element analysis meshing with 1922 quadrilateral 2D solid elements in ANSYS. Cracks are typically initiated in relation to the level of strain range. A higher strain range initiates cracks due to precipitate shearing, whereas a low strain range initiates cracks with oxidation reactions and carbide diffusion. The values of K1C and crack tip opening displacement for these alloys have been calculated based on the experimental data. Moreover, fracture morphology in the loading and unloading sequences near the crack tip has been analyzed by SEM.

The ability to use different parameters and finishing techniques in fused deposition modelling (FDM) depends largely on part geometries, materials, printing processes like Z-resolution and post processing to some extent. Low quality poor surface finish due to layer ovality, improper Z-resolution parameter selection and fill of the empty shell in three-dimensional (3D) printing, results unexpected texture and appearance. An investigation is carried out on the effects of Z-resolution (0.15 mm to 0.40 mm) and Fill parameters on flat and curved surface objects manufactured using the FDM process. Moreover, post surface treatment was performed using acetone. It was found that average surface roughness increases with increasing Z-resolution. Solid Fill can create a smoother surface as oppose to Sparse Fill. Surface roughness improves significantly after post treatment with organic solvent acetone.

Introduction: New anti-vascular endothelial growth factor (VEGF) treatments are emerging for the treatment of diabetic macular edema (DME)/neovascular age-related macular degeneration (nAMD). This study aimed to explore the treatment attributes patients find important when deciding on treatment options., Methods: This noninterventional survey study assessed treatment preferences through a discrete choice experiment (DCE) among patients with DME/nAMD in the United States, Canada, France, Italy, Spain, and the United Kingdom. The DCE design was informed by a targeted literature review and qualitative interview research and included five treatment attributes: mode of administration, frequency of examinations, frequency of injections or refills, likely change in visual acuity, and eye-related side effects. Conditional logit models were used to analyze the choice data., Results: Overall, 537 patients completed the DCE (DME, n = 173; nAMD, n = 364). Patients reported preferring "injection" over "implant surgery and refills" and better visual outcomes over "stabilization", which were also the most important attributes driving preference (35.1% and 31.5%, respectively). They also showed a preference for less-frequent treatment and examinations and for "mild-moderate, frequent" over "severe, rare" side effects. These findings were generally consistent across the two conditions, although significant differences were found depending on anti-VEGF treatment duration (nAMD, DME) and number of reported barriers (nAMD)., Conclusion: Patient preferences for treatment are driven by several factors. Considering these is essential when designing/introducing new therapies. Individual treatment preferences should be identified and given key consideration when helping patients select from an expanding array of treatment options., (The Author(s). Published by S. Karger AG, Basel.)

Introduction: Diabetic macular edema (DME) and neovascular age-related macular degeneration (nAMD) require frequent anti-vascular endothelial growth factor (VEGF) treatment and monitoring visits. We aimed to understand the burden of treatment on caregivers., Methods: This multinational, noninterventional study used a cross-sectional survey of adult patients with DME or nAMD treated with anti-VEGF injections in the USA, Canada, France, Italy, Spain, and the UK. The survey assessed caregivers' sociodemographic characteristics, patient relationships, patients' clinical history and treatment experiences, caregivers' experiences, and the Caregiver Reaction Assessment of caregiving burden., Results: Caregivers for patients with DME (n = 30) and nAMD (n = 95) completed surveys. Mean ± standard deviation (SD) age was 64.0 ± 13.4 years, and most were female (71.2%), white (70.4%), married (66.4%), and from Europe (67.2%). Most were caring for their mother/father or partner/spouse (85.6%). Mean ± SD length of time as a caregiver was 9.1 ± 10.0 years. Caregivers estimated they provided support for 4.2 ± 2.9 days/week and 6.0 ± 7.1 h/day on average. Nearly half of caregivers (45.6%) reported some impairment in daily activities, and more than two-thirds (70.5%) of working caregivers (n = 44) reported work absenteeism due to anti-VEGF treatment/monitoring appointments. At least one treatment barrier was reported by 66.7% and 50.5% of caregivers of patients with DME and nAMD, respectively, which were related to coronavirus disease 2019- (38.4%), clinic- (18.4%), social-/health- (13.6%), treatment- (10.4%), or financial-related factors (4.8%). Caregiver Reaction Assessment scores indicated mild-to-moderate burden, with higher caregiver schedule disruption scores associated with an increasing number of anti-VEGF treatment/monitoring visits among DME caregivers (r = 0.61)., Conclusion: Caregivers devote substantial time to caregiving, leading to schedule disruptions and absenteeism for some working caregivers. Positive and negative impacts on caregiver mental health were reported., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Introduction: Understanding patient perspectives of treatment may improve adherence and outcomes. This study explored real-world patient experiences with anti-vascular endothelial growth factor (anti-VEGF) treatment for diabetic macular edema (DME) and neovascular age-related macular degeneration (nAMD)., Methods: This multinational, non-interventional, quantitative, cross-sectional, observational survey assessed treatment barriers/burden, patient-reported visual functioning, and treatment satisfaction in DME and nAMD patients in the USA, the UK, Canada, France, Italy, and Spain. Treatment patterns and visual outcomes were extracted from medical charts. Regression models evaluated relationships between adherence, total missed visits, number of anti-VEGF injections, and clinical and patient-reported outcomes for visual functioning. Association between treatment satisfaction and aspects of burden were assessed., Results: The survey was completed by 183 DME and 391 nAMD patients. Patients had moderately high vision-related functioning (25-item National Eye Institute Visual Functioning Questionnaire score: mean = 74.8) and were satisfied with their current treatment (mean total score: Macular Disease Treatment Satisfaction Questionnaire = 59.2; Retinopathy Treatment Satisfaction Questionnaire = 61.3). Treatment satisfaction scores were worse with higher time-related impacts of treatment (nAMD/DME), higher impacts on finances and daily life (nAMD), negative impacts on employment and lower expectations for treatment effectiveness (DME). Most patients reported ≥1 barrier (66.1% DME, 49.2% nAMD patients) related to treatment (35.0%), clinic (32.6%), and COVID-19 (21.1%). Moreover, 44.9% of patients reported some impairment in activities of daily living. Work absenteeism was observed among >60% of working patients. Nearly one-quarter (24.2%) of patients needed ≥1 day to recover from intravitreal injections; most reported ≥30 min of travel time (73.7%) and clinic wait time (54.2%). In unadjusted univariable analyses, treatment adherence (vs. nonadherence) was related to higher most recent visual acuity (β = 8.98 letters; CI, 1.34-16.62) and lower odds of visual acuity below driving vision (≤69 letters) (OR = 0.50; CI, 0.25-1.00)., Conclusion: More durable treatments with reduced frequency of injections/visits may reduce treatment burden and improve patient satisfaction, which may enhance adherence and visual outcomes., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Introduction: Disease behaviour may guide diagnosis and treatment decisions in patients with interstitial lung disease (ILD). STARLINER aimed to characterise disease behaviour in patients with suspected ILD during the peri-diagnostic period using real-time home-based assessments., Methods: STARLINER (NCT03261037) was an international, multicentre study. Patients ≥ 50 years old with suspected ILD were followed throughout the peri-diagnostic period, consisting of a pre-diagnostic period (from enrolment to diagnosis) and a post-diagnostic period (from diagnosis to treatment initiation). Study length was variable (≤ 18 months). The primary endpoint was time-adjusted semi-annual forced vital capacity (FVC) change measured during the peri-diagnostic period using daily home spirometry in patients with idiopathic pulmonary fibrosis (IPF). Secondary outcomes included changes in FVC (home spirometry) in patients with non-IPF ILD, changes in FVC (site spirometry), changes in physical functional capacity measured by daily home accelerometry and site 6-min walk distance (6MWD), and changes in patient-reported outcomes (PROs) in IPF or non-IPF ILD., Results: Of the 178 patients enrolled in the study, 68 patients were diagnosed with IPF, 62 patients were diagnosed with non-IPF ILD, 9 patients received a non-ILD diagnosis and 39 patients did not receive a diagnosis. Technical and analytical issues led to problems in applying the prespecified linear regression model to analyse the home FVC data. Time-adjusted median (quartile [Q]1, Q3) semi-annual FVC change during the peri-diagnostic period measured using home and site spirometry, respectively, was - 147.7 (- 723.8, 376.2) ml and - 149.0 (- 314.6, 163.9) ml for IPF and 19.1 (- 194.9, 519.0) ml and - 23.4 (- 117.9, 133.5) ml in non-IPF ILD. A greater decline in steps per day was observed for IPF versus non-IPF ILD, whereas an increase in 6MWD was observed for patients with IPF versus a decline in 6MWD for patients with non-IPF ILD. No clear patterns of disease behaviour were observed for IPF versus non-IPF ILD for PROs., Conclusions: Despite home spirometry being feasible for most patients and centres, technical and analytical challenges in the home-based assessments prevented firm conclusions regarding disease behaviour. This highlights that further optimisation of the technology and analysis methods is required before widespread implementation., Trial Registration: NCT03261037., (© 2021. The Author(s).)

While pneumoperitoneum causes negative macrohaemodynamic effects, much less is known about microcirculatory effects of different anaesthetic techniques and laparoscopy. Therefore, we aimed to explore microcirculatory effects of combined spinal-general anaesthesia and laparoscopy, as measured by near-infrared spectroscopy over forearm and calf muscles utilising a 3-min ischemic challenge. Patients (n = 102) undergoing elective laparoscopic gynaecological surgery were randomised to receive general anaesthesia alone or in combination with high-dose or low-dose spinal analgesia (levobupivacaine 7.5 mg or 3.75 mg, respectively, plus sufentanil 2.5 μg). Primary outcomes were near-infrared spectroscopy derived parameters before general anaesthesia induction, 5 min after tracheal intubation, and 15 min after pneumoperitoneum commencement. General anaesthesia resulted in impaired post-ischaemic recovery rate in the forearm (p < 0.001, within all groups), which improved during laparoscopy. For the calf, before general anaesthesia induction, high and low dose spinal analgesia significantly slowed the post-ischaemic recovery compared to control (34 ± 16% min -1 and 36 ± 13% min -1 vs. 52 ± 27% min -1 , respectively; p = 0.002 and p = 0.006). General anaesthesia abolished differences between the groups (24 ± 14% min -1 and 25 ± 12% min -1 vs. 27 ± 18% min -1 ), while during laparoscopy high-dose spinal analgesia further reduced the post-ischaemic recovery compared to low-dose spinal and control groups (p = 0.023 and p = 0.040, respectively). During gynaecological laparoscopy patients show impaired calf but maintain forearm microcirculatory function, regardless of the anaesthetic technique. Reduction in post-ischaemic recovery with high-dose spinal analgesia is explained by its sympatholytic effects: number of perfused capillaries is increased, leading to a haemodynamically more favourable state. Blood pressure is positively correlated with the post-ischaemic recovery rate in vascular beds not affected by spinal analgesia.

Study Objective: We aimed to determine the magnitude of peri-operative opioid sparing effect when general anesthesia is combined with spinal analgesia for laparoscopic gynecological surgery., Design: A prospective randomized controlled study; a three-group trial with two comparisons (each intervention group to control)., Setting: Operating room and postoperative recovery area., Patients: Patients aged between 18 and 65 years with American Society of Anesthesiologists physical status 1 or 2 who were scheduled for inpatient elective laparoscopic gynecological surgery with expected pneumoperitoneum duration of at least 20 min. Of 102 randomized patients, 99 completed the study., Interventions: Patients were randomized to general anesthesia alone (control group) or combined with very-low-dose (levobupivacaine 3.75 mg; sufentanil 2.5 μg) or low-dose (levobupivacaine 7.5 mg; sufentanil 2.5 μg) spinal analgesia., Measurements: Primary endpoints were perioperative opioid consumption and pain scores (11-point numeric rating scale) at 30 min, 1 h, 2 h, 4 h and 24 h post-surgery. Secondary endpoints were patient satisfaction with anesthetic care and participation in research, sevoflurane consumption and adverse effects., Main Results: Intra-operative sufentanil (median [95% CI]) consumption was 16.1 (10.5-22.6) μg/h in the control group versus 4.7 (3.2-9.2) μg/h in the very-low-dose and versus 2.9 (0.0-4.0) μg/h in the low-dose spinal analgesia groups (p < 0.001, for both comparisons). Median (95% CI) piritramide consumption at 24 h post-surgery was 7.5 (3-8) mg in the control group versus 5 (0-7.5) mg in the very-low dose spinal analgesia group (p = 0.182) and versus 2 (0-2.5) mg in the low-dose spinal analgesia group (p = 0.001). Postoperative pain scores were consistently <3 only in the low dose spinal analgesia group. Patient satisfaction with anesthetic care and participation in research was very high in all groups., Conclusions: Low-dose spinal analgesia in combination with general anesthesia reduces peri-operative opioid consumption in laparoscopic gynecological surgery in immediate postoperative period., Competing Interests: Declaration of competing interest None., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: To establish whether the use of diclofenac reduces the administration of opioids and how it affects bleeding and platelet function after the coronary artery bypass grafting (CABG) surgery with use of cardiopulmonary bypass (CPB)., Methods: A total of 72 patients undergoing CABG surgery were included in this retrospective randomized study and divided into two groups (34 patients received diclofenac and the control group of 38 patients did not). For postoperative analgesia, both groups were prescribed opioids (piritramide). The primary endpoint was to establish the consumption of opioids. The secondary endpoint was to determine bleeding and the function of platelets 20 hours after the surgery., Results: The consumption of piritramide (diclofenac group 26±8 mg vs. control group 28±8 mg), the blood loss, and the function of platelets did not significantly differ between the groups within 20 hours after surgery. C-reactive protein (CRP) was statistically significantly lower in the diclofenac group than in the control group (33±15 mg/L vs. 46±22 mg/L, respectively, P<0.05)., Conclusion: The study concluded that patients administered with diclofenac after the heart surgery did not consume less opioid analgesics and did not exhibit less symptoms linked to the consumption of opioids. Diclofenac in clinically administered doses does not interfere with the function of platelets and does not cause increased bleeding. Lower CRP in the diclofenac group may indicate a reduced inflammatory response after CPB. Therefore, diclofenac could be safe for use in patients undergoing CABG surgery but its value in reducing opioid consumption should be questioned.

Background: We studied the influence of ephedrine or phenylephrine infusion administered immediately after spinal anesthesia (SA) on hemodynamics in elderly orthopedic patients., Methods: A prospective, randomized, double-blind, placebo-controlled study. After a subarachnoid injection of 15 mg of levobupivacaine, the participants received an infusion of either ephedrine 20 mg (E group), phenylephrine 250 mcg (P group) or saline (C group) within 30 min. We measured blood pressure, cardiac index (CI) and heart rate (HR) from 15 min before to 30 min after SA., Results: Seventy patients were included in the final analysis. At the end of measurements, mean arterial pressure (MAP) decreased significantly after SA in comparison to the baseline value in the C group but was maintained in the P and E group, with no significant differences between the groups. CI decreased after SA in the C group, was maintained in the P group, and increased significantly in the E group with significant differences between the C and E group (p = 0.049) also between the P and E (p = 0.01) group at the end of measurements. HR decreased significantly after SA in the C and P group but was maintained in the E group, with significant differences between the P and E group (p = 0.033) at the end of measurements., Conclusions: Hemodynamic changes after SA in elderly orthopedic patients can be prevented by an immediate infusion of phenylephrine or ephedrine. In addition to maintaining blood pressure, the ephedrine infusion also maintains HR and increases CI after SA., Trial Registration: ISRCTN registry with registration number ISRCTN44377602, retrospectively registered on 15 June 2017.

Development of novel DNA gyrase B inhibitors is an important field of antibacterial drug discovery whose aim is to introduce a more effective representative of this mechanistic class into the clinic. In the present study, two new series of Escherichia coli DNA gyrase inhibitors bearing the 4,5-dibromopyrrolamide moiety have been designed and synthesized. 4,5,6,7-Tetrahydrobenzo[1,2-d]thiazole-2,6-diamine derivatives inhibited E. coli DNA gyrase in the submicromolar to low micromolar range (IC 50 values between 0.891 and 10.4μM). Their "ring-opened" analogues, based on the 2-(2-aminothiazol-4-yl)acetic acid scaffold, displayed weaker DNA gyrase inhibition with IC 50 values between 15.9 and 169μM. Molecular docking experiments were conducted to study the binding modes of inhibitors., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Introduction: The cardiovascular response to decreased or increased preload in high-risk patients with ischemic heart disease enables us to understand the physiologic response to hemorrhage and its treatment. Although numerous studies have failed to show its effectiveness, the head-down position is still widely used to treat patients with hypotension and shock. The aim of our study was to evaluate the influence of body position on hemodynamics in high-risk patients undergoing coronary artery bypass graft surgery., Methods: In 16 patients with ischemic hearth disease and poor left ventricular function undergoing coronary artery bypass graft surgery, we measured cardiac output with thermodilution, arterial pressure, central venous pressure (CVP), pulmonary artery wedge pressure (PAWP) and heart rate in three different body positions: the horizontal position, 20 degrees head-up position, 20 degrees head-down position and back in the horizontal position. The measurements were made before and after cardiac surgery., Results: Before skin incision the change from horizontal to 20 degrees head-up position led to a nonsignificant decrease in cardiac output and a significant decrease in mean arterial pressure, CVP and PAWP. The change from 20 degrees head-up to 20 degrees head-down position led to a significant increase in cardiac output, mean arterial pressure, CVP and PAWP. After skin closure the change from horizontal to 20 degrees head-up position led to a nonsignificant decrease in cardiac output and mean arterial pressure and a significant decrease CVP and PAWP. The change from 20 degrees head-up to 20 degrees head-down position led to a nonsignificant increase in cardiac output and a significant increase in mean arterial pressure, CVP and PAWP. There were no significant changes in heart rate during the changes in position before or after surgery., Conclusions: The results of our study showed a hemodynamic response similar to hemorrhage after placing the patients in a 20 degrees head-up position and improving hemodynamics in the head-down position in mechanically ventilated patients undergoing coronary artery bypass graft surgery.

Background and Objectives: Acute zoster pain usually disappears with regression of the rash but may be of significant intensity and prolonged duration leading to postherpetic neuralgia. We evaluated the effect of pregabalin on alleviation of acute zoster pain and onset of postherpetic neuralgia., Methods: The prospective randomized double-blind placebo-controlled study included 29 outpatients who had had acute zoster pain for a period of 7-14 days. Patients were treated for three weeks with 150-300 mg pregabalin daily or with a placebo. Pain was treated with naproxen, tramadol or oxycodone, as necessary. During the treatment we assessed pain, allodynia, hyperalgesia, severity of burning, prickling and tingling sensations, quality of sleep, physical activity, consumption of analgesics, manifestation of adverse events and postherpetic neuralgia., Results: There were no statistically significant differences with respect to patients' demographic data, dermatomal distribution and severity of rash, use of antiviral therapy or duration of acute zoster pain. Standard statistical analyses found no significant differences between the two treatment groups in intensity of pain, allodynia, hyperalgesia, burning, prickling and tingling sensations, consumption of analgesics, or the quality of sleep and physical activity; there was also no significant difference in development of postherpetic neuralgia. However, there were statistically significant differences between the groups in the occurrence of dizziness and somnolence in relation to pregabalin., Conclusion: The study did not prove any statistically significant effect of pregabalin in pain relief in patients with acute zoster pain or in the onset of postherpetic neuralgia in comparison with the placebo. The use of pregabalin was related to a statistically significant increase in the appearance of adverse effects.

Background: The aim of our study was to evaluate the effects of Trendelenburg position, infusion of 6% hydroxyetyl starch solution or lactated Ringer's solution on changes in cardiac output (CO) after spinal anesthesia in patients older than 50 yr., Methods: Seventy patients scheduled for lower extremity orthopedic surgery under spinal anesthesia were allocated randomly to one of the three treatment groups. In the Trendelenburg group, the patients were placed in the Trendelenburg position immediately after the spinal block for 10 min. In the hydroxyethyl starch group and the lactated Ringer's group, the patients received an infusion of 500 mL of 6% hydroxyethyl starch solution or 1000 mL of lactated Ringer's solution over 20 min after the spinal block. CO was measured continuously from 15 min before until 30 min after spinal anesthesia using the impedance cardiography method and arterial blood pressure with an automated device. P < 0.05 was considered statistically significant., Results: The differences among treatment groups in CO were not statistically significant. Differences in the CO changes from baseline over time were significant. In the Trendelenburg group, CO did not change while the patient was in the Trendelenburg position. In the hydroxyethyl starch group, CO increased significantly after the block and remained significantly increased until the end of measurements. In the lactated Ringer's group, CO increased significantly 10 and 20 min after the block but, after stopping the infusion, CO started to decrease., Conclusions: Our study demonstrated that a decrease in CO after spinal anesthesia is prevented by placing the patient in the Trendelenburg position, or infusion of either lactated Ringer's solution or 6% hydroxyetyl starch solution. Although the effects of the infusion of the lactated Ringer's solution are transient, the effects of the infusion of 6% hydroxyethyl starch solution are extended beyond the time the infusion.

Serotonin syndrome commonly follows irreversible monoamine oxidase (MAO)-inhibition and subsequent serotonin (5-HT) substrate (in rats with fore paw treading, hind limbs abduction, wet dog shake, hypothermia followed by hyperthermia). A stable gastric pentadecapeptide BPC 157 with very safe profile (inflammatory bowel disease clinical phase II, PL-10, PLD-116, PL-14736, Pliva) reduced the duration of immobility to a greater extent than imipramine, and, given peripherally, has region specific influence on brain 5-HT synthesis (alpha-[14C]methyl-L-tryptophan autoradiographic measurements) in rats, different from any other serotonergic drug. Thereby, we investigate this peptide (10 microg, 10 ng, 10 pg/kg i.p.) in (i) full serotonin syndrome in rat combining pargyline (irreversible MAO-inhibition; 75 mg/kg i.p.) and subsequent L-tryptophan (5-HT precursor; 100 mg/kg i.p.; BPC 157 as a co-treatment), or (ii, iii) using pargyline or L-tryptophan given separately, as a serotonin-substrate with (ii) pargyline (BPC 157 as a 15-min posttreatment) or as a potential serotonin syndrome inductor with (iii) L-tryptophan (BPC 157 as a 15 min-pretreatment). In all experiments, gastric pentadecapeptide BPC 157 contrasts with serotonin-syndrome either (i) presentation (i.e., particularly counteracted) or (ii) initiation (i.e., neither a serotonin substrate (counteraction of pargyline), nor an inductor for serotonin syndrome (no influence on L-tryptophan challenge)). Indicatively, severe serotonin syndrome in pargyline + L-tryptophan rats is considerably inhibited even by lower pentadecapeptide BPC 157 doses regimens (particularly disturbances such as hyperthermia and wet dog shake thought to be related to stimulation of 5-HT2A receptors), while the highest pentadecapeptide dose counteracts mild disturbances present in pargyline rats (mild hypothermia, feeble hind limbs abduction). Thereby, in severe serotonin syndrome, gastric pentadecapeptide BPC 157 (alone, no behavioral or temperature effect) has a beneficial activity, which is likely, particular, and mostly related to a rather specific counteraction of 5-HT2A receptors phenomena.

Introduction: In a prospective randomised trial we studied haemodynamic stability during induction of anaesthesia for CABG surgery in patients receiving remifentanil-propofol or fentanyl-propofol anaesthesia., Methods: Fifty-four patients scheduled for elective CABG surgery were studied. Anaesthesia was induced with propofol and pancuronium. The patients were randomly assigned to two groups according to the opioid used during the induction. The remifentanil group received 0.5 microg kg(-1) min(-1) of the drug and the fentanyl group received 5 microg kg(-1). We measured blood pressure, central venous pressure and heart rate continuously for 15 min before and 30 min after orotracheal intubation. We also recorded use of rescue medication for maintaining the mean arterial pressure between 65 and 85 mmHg., Results: After induction of anaesthesia the mean arterial pressure and heart rate decreased significantly in both groups (P<0.05). After orotracheal intubation the mean arterial pressure and heart rate increased significantly in the fentanyl group but not in the remifentanil group (P<0.05). The incidence of hypertonic events necessitating the use of rescue medication was significantly higher in the fentanyl group (P<0.05)., Conclusions: Our results show more stable haemodynamics after induction of anaesthesia in CABG surgery in patients receiving remifentanil-propofol than in patients receiving fentanyl-propofol.

We investigated the prevalence of DPC4 loss of heterozygosity in sporadic colorectal cancer. Thirty-six cases of human sporadic colon carcinoma and corresponding normal tissue samples were examined to evaluate loss of heterozygosity at the DPC4 tumor suppressor locus using variable nucleotide tandem repeat (VNTR) analysis and three polymorphic markers. From 36 analyzed samples 35 (97%) were heterozygous or informative. Loss of heterozygosity at the DPC4 locus was detected in 18 (51%) of informative tumor DNAs. The DPC4 LOH was more frequent in smaller tumors (<5 cm) than in larger ones. There was no correlation between DPC4 LOH and age or sex of patients. There was a negative correlation between DPC4 LOH and histological grade or Dukes' stage of tumors, but without statistic significance. Observed results are in agreement with the view that malignant progression is consequence of many genetic changes. It can be concluded that inactivation of the DPC4 gene plays a role in a multistep process of outgrowth and progression of colon cancer.