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Selected AbstractsA reliable externally fixated murine femoral fracture model that accounts for variation in movement between animalsJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 5 2003Chris K. Connolly Abstract Fifty-two CFLP mice had an open femoral diaphyseal osteotomy held in compression by a four-pin external fixator. The movement of 34 of the mice in their cages was quantified before and after operation, until sacrifice at 4, 8, 16 or 24 days. Thirty-three specimens underwent histomorphometric analysis and 19 specimens underwent torsional stiffness measurement. The expected combination of intramembranous and endochondral bone formation was observed, and the model was shown to be reliable in that variation in the histological parameters of healing was small between animals at the same time point, compared to the variation between time-points. There was surprisingly large individual variation in the amount of animal movement about the cage, which correlated with both histomorphometric and mechanical measures of healing. Animals that moved more had larger external calluses containing more cartilage and demonstrated lower torsional stiffness at the same time point. Assuming that movement of the whole animal predicts, at least to some extent, movement at the fracture site, this correlation is what would be expected in a model that involves similar processes to those in human fracture healing. Models such as this, employed to determine the effect of experimental interventions, will yield more information if the natural variation in animal motion is measured and included in the analysis. © 2003 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved. [source] Transhepatic lactate gradient in relation to liver ischemia/reperfusion injury during major hepatectomiesLIVER TRANSPLANTATION, Issue 12 2006Kassiani Theodoraki Hepatectomies performed under selective hepatic vascular exclusion are associated with a series of events culminating in ischemia/reperfusion injury, a state that shares common characteristics with situations known to result in global or regional hyperlactatemia. Accordingly, we sought to determine whether lactate is released by the liver during hepatic resections performed under blood flow deprivation and what relation this has to a possible systemic hyperlactatemic state. After ethical approval, 14 consecutive patients with resectable liver tumors subjected to hepatectomy under inflow and outflow occlusion of the liver were studied. Lactate concentrations were assessed in simultaneously drawn arterial, portal venous, and hepatic venous blood before liver dissection and 50 minutes postreperfusion. Moreover, the transhepatic lactate gradient (hepatic vein , portal vein) was calculated to see if there was net production or consumption of lactate. Before hepatic dissection, the transhepatic lactate gradient was negative, suggesting consumption by the liver. Fifty minutes after reperfusion, this gradient became significantly positive, demonstrating release of lactate by the liver (0.12 ± 0.31 vs. ,0.38 ± 0.30 mmol/L, P < 0.05). The magnitude of lactate release correlated with systemic arterial lactate levels at the same time point (r2 = 0.63, P < 0.001). A weaker but significant correlation was demonstrated between the transhepatic lactate gradient postreperfusion and systemic arterial lactate levels 24 hours postoperatively (r2 = 0.41, P = 0.013). A strong correlation between the transhepatic lactate gradient postreperfusion and peak postoperative aspartate aminotransferase values was also demonstrated (r2 = 0.73, P < 0.001). The liver becomes a net producer of lactate in hepatectomies performed under blood flow deprivation. This lactate release can explain some of the systemic hyperlactatemia seen in this context and relates to the extent of ischemia/reperfusion injury. Liver Transpl 12:1825-1831, 2006. © 2006 AASLD. [source] Equivalence of hydroxyethyl starch HES 130/0.ACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 9 2003HES 200/0. Background:, Hydroxyethyl starch solutions (HES) are increasingly used for the compensation of surgical blood loss. The objective of this clinical trial was to compare a novel 6% HES 130/0.4 solution with a favourable pharmacological profile and a standard 6% HES 200/0.5 solution for maintenance of haemodynamic stability in major gynaecological surgery. Methods:, Sixty female patients aged 18,80 years undergoing major gynaecological surgery with indication for perioperative colloidal volume replacement were enrolled in this prospective, randomized double-blinded clinical study. The administration of study medication was dependent on individual requirements to maintain haemodynamic stability. The amount of study medication required from induction of anaesthesia until 6 h postoperatively served as the primary investigative parameter. Results:, The two one-sided test procedure by Westlake demonstrated equivalence of mean infused volumes between HES 130/0.4 and HES 200/0.5 during the study period (1224 ± 544 ml and 1389 ± 610 ml, respectively, P < 0.05). Perioperatively, haemodynamics did not differ significantly between treatment groups. While none of the mean values of coagulation parameters shifted outside the normal range, the degree of haemodilution revealed reduced haematocrit values in HES 200/0.5 treated patients at 6 h postoperatively (P < 0.05). Moreover, prothrombin time (PT) was higher and consequently international normalized ratio (INR) was lower at the same time point for patients who received HES 130/0.4 (P < 0.05). Conclusion:, This clinical trial demonstrated therapeutic equivalence of this novel low-substituted HES 130/0.4 solution and a standard HES 200/0.5 solution for perioperative volume replacement. Moreover, both HES preparations were equally well-tolerated and safe. [source] Role of Complement Anaphylatoxin C3a in Photodynamic Therapy-elicited Engagement of Host Neutrophils and Other Immune CellsPHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 2 2006Ivana Cecic ABSTRACT Tumor treatment by photodynamic therapy (PDT) provokes a host-protective inflammatory and acute-phase response and an immune reaction. Neutrophilia manifested in this context is driven by multiple mediators of neutrophil chemotaxis orchestrated by an activated complement system. Mouse FsaR fibrosarcoma was used in this study to further investigate neutrophilia induced by Photofrin-based PDT. The complement anaphylatoxin C3a was identified as a major chemo-attractant in the advanced phase of PDT-induced neutrophilia, because injecting mice with antibodies blocking its receptor C3aR significantly inhibited the increase in neutrophil levels 8 h after PDT. At the same time point, an increased C3aR expression was detected in neutrophils, monocytes and B lymphocytes in the blood of host mice. Peritoneal macro-phages and mast cells harvested from treatment-naive mice exhibited elevated C3aR expression after coincubation in vitro for 8 h with PDT-treated FsaR cells. Thus, C3a emerges as one of the key effector molecules engaged in PDT-induced host response. [source] Cell Cycle Progression in Serum-Free Cultures of Sf9 Insect Cells: Modulation by Conditioned Medium Factors and Implications for Proliferation and Productivity,BIOTECHNOLOGY PROGRESS, Issue 5 2000Magnus Doverskog Cell cycle progression was studied in serum-free batch cultures of Spodoptera frugiperda (Sf9) insect cells, and the implications for proliferation and productivity were investigated. Cell cycle dynamics in KBM10 serum-free medium was characterized by an accumulation of 50,70% of the cells in the G2/M phase of the cell cycle during the first 24 h after inoculation. Following the cell cycle arrest, the cell population was redistributed into G1 and in particular into the S phase. Maximum rate of proliferation (,N,max) was reached 24,48 h after the release from cell cycle arrest, coinciding with a minimum distribution of cells in the G2/M phase. The following declining ,N could be explained by a slow increase in the G2/M cell population. However, at approximately 100 h, an abrupt increase in the amount of G2/M cells occurred. This switch occurred at about the same time point and cell density, irrespective of medium composition and maximum cell density. An octaploid population evolved from G2/M arrested cells, showing the occurrence of endoreplication in this cell line. In addition, conditioned medium factor(s) were found to increase ,N,max, decrease the time to reach ,N,max, and decrease the synchronization of cells in G2/M during the lag and growth phase. A conditioned medium factor appears to be a small peptide. On basis of these results we suggest that the observed cell cycle dynamics is the result of autoregulatory events occurring at key points during the course of a culture, and that entry into mitosis is the target for regulation. Infecting the Sf9 cells with recombinant baculovirus resulted in a linear increase in volumetric productivity of ,-galactosidase up to 68,75 h of culture. Beyond this point almost no product was formed. Medium renewal at the time of infection could only partly restore the lost hypertrophy and product yield of cultures infected after the transition point. The critical time of infection correlated to the time when the mean population cell volume had attained a minimum, and this occurred 24 h before the switch into the G2/M phase. We suggest that the cell density dependent decrease in productivity ultimately depends on the autoregulatory events leading to G2/M cell cycle arrest. [source] Differential effects of glucose on agonist-induced relaxations in human mesenteric and subcutaneous arteriesBRITISH JOURNAL OF PHARMACOLOGY, Issue 3 2008A MacKenzie Background and purpose: Acute periods of hyperglycaemia are strongly associated with vascular disorder, yet the specific effects of high glucose on human blood vessel function are not fully understood. In this study we (1) characterized the endothelial-dependent relaxation of two similarly sized but anatomically distinct human arteries to two different agonists and (2) determined how these responses are modified by acute exposure to high glucose. Experimental approach: Ring segments of human mesenteric and subcutaneous arteries were mounted in a wire myograph. Relaxations to acetylcholine and bradykinin were determined in a control (5 mM) and high glucose (20 mM) environment over a 2 and 6 h incubation period. Key results: Bradykinin-induced relaxation in both sets of vessels was mediated entirely by EDHF whilst that generated by acetylcholine, though principally generated by EDHF, also had contribution from prostacyclin and possibly nitric oxide in mesenteric and subcutaneous vessels, respectively. A 2-h incubation of high glucose impaired bradykinin-induced relaxation of subcutaneous vessels whilst, in contrast, the relaxation generated by bradykinin in mesenteric vessels was enhanced at the same time point. High glucose significantly augmented the relaxation generated by acetylcholine in mesenteric and subcutaneous vessels at a 2 and 6 h incubation point, respectively. Conclusions and implications: Short periods of high glucose exert a variable influence on endothelial function in human isolated blood vessels that is dependent on factors of time, agonist-used and vessel studied. This has implications for how we view the effects of acute hyperglycaemia found in patients with diabetes mellitus as well as other conditions. British Journal of Pharmacology (2008) 153, 480,487; doi:10.1038/sj.bjp.0707592; published online 26 November 2007 [source] Sub-millimolar concentration of the novel phenol-based compound, 2-hydroxy benzoate zinc, induces apoptosis in human HT-1080 fibrosarcoma cellsCELL PROLIFERATION, Issue 1 2010J. G. Mahdi Objectives:, To examine the effect of a novel phenolic-based compound, 2-hydroxy benzoate zinc (2HBZ), and acetylsalicylic acid (ASA) on human HT-1080 fibrosarcoma cells. Materials and methods:, MTT assay was used to assess cell proliferation while different methods were used to detect apoptosis morphologically and immunohistochemically in Human HT-1080 fibrosarcoma cells. Apoptosis was determined by Annexine-V labelling, and caspase-3 activation. In addition, western blot was used to analyse p21, p53 and Bax and flow cytometry was to analyse the cell cycle. Results:, 2HBZ exhibited a more than 5-fold increase in cytotoxic potency when compared with ASA with mean LD50 values of 210 and 1100 lM respectively (P < 0.0001). The cytotoxic effects of 2HBZ were both time- and dosedependent with marked apoptosis being evident only after 24 h at concentrations as low as 200 mM. In contrast, ASA-induced apoptosis was observed only at concentrations in excess of 1000 mM at the same time point. Both 2HBZ and ASA induced caspase-3 activation in the cells, which confirmed that their cytotoxic effects were the result of apoptotic cell death. These findings were further confirmed by immunomorphological studies for the detection of apoptosis including haematoxylineosin, methyl green/pyronin Y staining and scanning electron microscopy. In addition, 2HBZ caused a marked increase in p21, p53 and Bax protein expressions and these effects were associated with an increase in G1 and G2 arrest of the cell cycle and a reduction in S-phase. Conclusions:, These results demonstrate that the novel phenolic compound 2HBZ is a potent apoptosis-inducing agent in HT-1080 cells and warrants further investigation as a potential chemotherapeutic agent in primary cancer cell models. [source] BDNF,triggered events in the rat hippocampus are required for both short- and long-term memory formationHIPPOCAMPUS, Issue 4 2002Mariana Alonso Abstract Information storage in the brain is a temporally graded process involving different memory types or phases. It has been assumed for over a century that one or more short-term memory (STM) processes are involved in processing new information while long-term memory (LTM) is being formed. Because brain-derived neutrophic factor (BDNF) modulates both short-term synaptic function and activity-dependent synaptic plasticity in the adult hippocampus, we examined the role of BDNF in STM and LTM formation of a hippocampal-dependent one-trial fear-motivated learning task in rats. Using a competitive RT-PCR quantitation method, we found that inhibitory avoidance training is associated with a rapid and transient increase in BDNF mRNA expression in the hippocampus. Bilateral infusions of function-blocking anti-BDNF antibody into the CA1 region of the dorsal hippocampus decreased extracellular signal,regulated kinase 2 (ERK2) activation and impaired STM retention scores. Inhibition of ERK1/2 activation by PD098059 produced similar effects. In contrast, intrahippocampal administration of recombinant human BDNF increased ERK1/2 activation and facilitated STM. The infusion of anti-BDNF antibody impaired LTM when given 15 min before or 1 and 4 hr after training, but not at 0 or 6 hr posttraining, indicating that two hippocampal BDNF-sensitive time windows are critical for LTM formation. At the same time points, PD098059 produced no LTM deficits. Thus, our results indicate that endogenous BDNF is required for both STM and LTM formation of an inhibitory avoidance learning. Additionally, they suggest that this requirement involves ERK1/2-dependent and -independent mechanisms. Hippocampus 2002;12:551,560. © 2002 Wiley-Liss, Inc. [source] Hyper osmolality does not modulate natriuretic peptide concentration in patients after coronary artery surgeryACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 5 2009E. L. HONKONEN Background: The heart secretes natriuretic peptides (NPs) in response to myocardial stretch. Measuring NP concentrations is a helpful tool in guiding treatment. It has been suggested that sodium ion and hyperosmolality could affect NP excretion. If this is true, peri-operative NP measurements could be inconsistent when hypertonic solutions are used. With different osmolalities but equal volumes of hydroxyethyl starch (HES) , and hypertonic saline (HS) , infusions, this double-blinded study tested the hypothesis that osmolality modulates the excretion of NPs. Methods: Fifty coronary surgery patients were randomized to receive within 30 min 4 ml/kg either HS or HES post-operatively. Samples for analysis of atrial NP (ANP), brain NP (BNP), plasma and urine sodium and osmolality and urine oxygen tension were obtained before and 60 min after starting the infusions and on the first post-operative morning. The haemodynamic parameters were measured at the same time points. Results: Plasma osmolality and sodium increased only in the HS group. Changes in plasma BNP and ANP levels did not differ between the groups (P=0.212 and 0.356). There were no correlations between NP levels and osmolality or sodium at any time point. In the HS group, urine volume was higher (3295 vs. 2644 ml; P<0.05) and the need for furosemide treatment was less (0.4 vs. 3.8 mg; P<0.01) than in the HES group. Conclusions: The absence of effects of plasma sodium content or hyperosmolality on NP release validates the value of NPs as a biomarker in peri-operative patients. [source] Crushed Clopidogrel Administered via Nasogastric Tube Has Faster and Greater Absorption than Oral Whole TabletsJOURNAL OF INTERVENTIONAL CARDIOLOGY, Issue 4 2009M. UROOJ ZAFAR M.B.B.S. Objectives: To compare the absorption of 300 mg clopidogrel administered crushed via nasogastric (NG) tube versus whole tablets taken orally in healthy volunteers. Background: Earlier antiplatelet therapy has proven benefits in treatment of myocardial infarction and in patients undergoing PCI. Aspirin can be delivered early in crushed form via NG tube after CABG surgery to prevent graft occlusion. If clopidogrel given crushed via NG tube provides faster absorption, it could allow earlier clopidogrel loading. Methods: Nine healthy human subjects (34.7 ± 11.1 years, 5 males) were given 300 mg clopidogrel in crushed form via NG tube with 30 mL water after 8 hours of fasting. Plasma levels of the primary circulating inactive clopidogrel metabolite SR26334 were measured after 20 minutes, 40 minutes, 1, 2, 4, 8, 12, and 24 hours of dosing. Following ,2 week washout, same subjects swallowed 300 mg clopidogrel (four 75 mg tablets) after an 8-hour fasting and SR26334 levels were measured at the same time points. Results: Plasma SR26334 concentrations peaked earlier after crushed delivery than after oral intake (44 vs. 70 minutes, P = 0.023) and the median peak was 80% higher (13,083 vs. 7,255 ng/mL, respectively, P = 0.021). At 40 minutes, area under the curve was almost twofold greater with NG administration than oral administration (geometric means ratio = 0.5299, 95% CI = 0.28,0.99, P = 0.048), but was similar over the 24-hour period with both administration methods (geometric means ratio = 1.05, 95% CI = 0.84,1.32, P = 0.646). Conclusions: A 300 mg loading dose of crushed clopidogrel administered via NG tube provides faster and greater bioavailability than an equal dose taken orally as whole tablets. The clinical benefits of this strategy need to be investigated. [source] Field efficacy of a 10 per cent pyriproxyfen spot-on for the prevention of flea infestations on catsJOURNAL OF SMALL ANIMAL PRACTICE, Issue 10 2001L. Maynard The clinical application of a new method for using the insect growth regulator, pyriproxyfen, for controlling flea populations in cat-owning homes is evaluated for the first time. In a multicentric, controlled and randomised trial, 107 flea-infested cats were treated with a minimum dose of 10 mg/kg bodyweight pyriproxyfen as a 10 per cent spot-on application on two occasions, with a three-month interval between doses. For comparison, 99 cats received lufenuron suspension orally, once a month, for six months. Flea counts decreased significantly over time in each group and were significantly lower in the pyriproxyfen group than in cats treated with the reference product. The percentage of ,zero-flea' cats increased from 49 per cent on day 30 to 88 per cent on day 180 in the pyriproxyfen group and from 30 to 71 per cent in the lufenuron group at the same time points (P<0,05). Appropriately timed topical applications of pyriproxyfen, therefore, offer a method of flea control in the domestic environment. [source] The impact of serum sodium concentration on mortality after liver transplantation: A cohort multicenter study,LIVER TRANSPLANTATION, Issue 8 2007Muhammad F. Dawwas Modification of the current allocation system for donor livers in the United States to incorporate recipient serum sodium concentration ([Na]) has recently been proposed. However, the impact of this parameter on posttransplantation mortality has not been previously examined in a large risk-adjusted analysis. We assessed the effect of recipient [Na] on the survival of all adults with chronic liver disease who received a first single organ liver transplant in the UK and Ireland during the period March 1, 1994 to March 31, 2005 (n = 5,152) at 3 years, during the first 90 days, and beyond the first 90 days, adjusting for a wide range of recipient, donor, and graft characteristics. Compared to those with normal [Na] (135,145 meq/L; n = 3,066), severely hyponatremic recipients ([Na] <130 meq/L, n = 541), had a higher risk-adjusted mortality at 3 years (hazard ratio [HR] 1.28; 95% confidence interval [CI], 1.04,1.59; P < 0.02). The excess mortality was, however, confined to the first 90 days (HR 1.55; 95% CI, 1.18,2.04; P < 0.002) with no significant difference thereafter. This was also true for hypernatremic recipients ([Na] >145 meq/L, n = 81), who had an even greater risk-adjusted mortality compared to normonatremic recipients (overall: HR 1.85; 95% CI, 1.25,2.73; P < 0.002; ,90 days: HR 2.29; 95% CI, 1.42,3.70; P < 0.001; >90 days: HR 1.12; 95% CI, 0.55,2.29; P = 0.8), whereas mildly hyponatremic recipients ([Na] 130,134 meq/L, n = 1,127) had similar risk-adjusted mortality to those with normal [Na] at the same time points. In conclusion, recipient [Na] is an independent predictor of death following liver transplantation. Attempts to correct the [Na] toward the normal reference range are an important aspect of pretransplantation management. Liver Transpl 13:1115,1124, 2007. © 2007 AASLD. [source] Effects of sodium benzoate on the complications of 1.ACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 4 20045% glycine solution using two different intravesical pressures during bladder irrigation Background:, In this experimental study we researched the effects of sodium benzoate on the complications of 1.5% glycine solution using with two different intravesical pressures during bladder irrigation. Methods:, Thirty-six male adult New Zealand rabbits with body weight ranging from 1500 to 2800 g were used in the experiments. The rabbits were randomly allocated to four groups. In groups 1 and 2, 500 ml of 1.5% gylcine was used as irrigating fluid during 30 min, but only group 2 received 500 mg kg,1 of sodium benzoate treatment by oral route immediately after irrigation. In groups 3 and 4, 500 ml of 1.5% glycine was used as irrigating fluid during 60 min, but only group 4 received the same treatment as group 2. Ammonia, urea, sodium, potassium, hemoglobin, hemotocrit and platelet levels were studied at preirrigation and postirrigation on the 4 h and 24 h. Also electrocardiographic (ECG) changes were monitored at the same time with blood parameters. Results:, At 4 h postirrigation, Na+ levels were decreased significantly in group 1 and non-significantly in group 3 when compared with preirrigation levels. But these levels were not changed in groups 2 and 4. Both at 4 h and 24 h, ammonia and urea levels were significantly increased in groups 1 and 3. Ammonia level was decreased but the urea level was not changed in groups 2 and 4 at the same time points. K+ level was significantly changed only in group 1 at 4 h and 24 h. Hemoglobin and hemotocrit concentrations were decreased both at 4 h and 24 h compared with preirrigation levels in all groups. Also there were ECG changes between the treated and untreated groups. Conclusion:, Sodium benzoate was very effective against the complications of 1.5% glycine during bladder irrigation experimentally. But this needs further investigation, especially for the applicability of this new treatment model in human TURP syndrome. [source] Increasing oncologists' skills in eliciting and responding to emotional cues: evaluation of a communication skills training program,PSYCHO-ONCOLOGY, Issue 3 2008Phyllis Butow Abstract Purpose: Psychological morbidity in cancer patients is common, but often undetected and untreated. We developed a communication skills training (CST) program targeting this issue, and evaluated its impact on doctor behaviour. Patients and Methods: Thirty of 35 oncologists from six teaching hospitals in six Australian cities, participated. The CST was a 1.5-day intensive face-to-face workshop incorporating presentation of principles, a DVD modelling ideal behaviour and role-play practice, followed by four 1.5 h monthly video-conferences incorporating role-play of doctor-generated scenarios. Doctors were randomized to receive the CST or not. Simulated patient interviews were videotaped and coded at baseline, after CST and 6 months later. Doctors completed questionnaires assessing stress and burnout at the same time points. Results: Doctors in the intervention group displayed more creating environment and fewer blocking behaviours at both follow-ups; however, these differences did not reach statistical significance. Intervention doctors valued the training highly, but did not report substantial reductions in stress and burnout. Conclusions: This short training programme demonstrated a positive effect on aspects of doctor behaviour. Video-conferencing after a short training course may be an effective strategy for delivering CST. Copyright © 2007 John Wiley & Sons, Ltd. [source] Exercise induces expression of leukaemia inhibitory factor in human skeletal muscleTHE JOURNAL OF PHYSIOLOGY, Issue 8 2008Christa Broholm The leukaemia inhibitory factor (LIF) belongs to the interleukin (IL)-6 cytokine superfamily and is constitutively expressed in skeletal muscle. We tested the hypothesis that LIF expression in human skeletal muscle is regulated by exercise. Fifteen healthy young male volunteers performed either 3 h of cycle ergometer exercise at ,60% of (n= 8) or rested (n= 7). Muscle biopsies were obtained from the vastus lateralis prior to exercise, immediately after exercise, and at 1.5, 3, 6 and 24 h post exercise. Control subjects had biopsy samples taken at the same time points as during the exercise trial. Skeletal muscle LIF mRNA increased immediately after the exercise and declined gradually during recovery. However, LIF protein was unchanged at the investigated time points. Moreover, we tested the hypothesis that LIF mRNA and protein expressions are modulated by calcium (Ca2+) in primary human skeletal myocytes. Treatment of myocytes with the Ca2+ ionophore, ionomycin, for 6 h resulted in an increase in both LIF mRNA and LIF protein levels. This finding suggests that Ca2+ may be involved in the regulation of LIF in endurance-exercised skeletal muscle. In conclusion, primary human skeletal myocytes have the capability to produce LIF in response to ionomycin stimulation and LIF mRNA levels increase in skeletal muscle following concentric exercise. The finding that the increase in LIF mRNA levels is not followed by a similar increase in skeletal muscle LIF protein suggests that other exercise stimuli or repetitive stimuli are necessary in order to induce a detectable accumulation of LIF protein. [source] Preoperative topical cyclopentolate can be omitted when using intracameral lidocaine in phacoemulsification surgeryACTA OPHTHALMOLOGICA, Issue 3 2009Björn Lundberg Abstract. Purpose:, To evaluate the mydriatic effect of topical cyclopentolate 1% when combined with topical phenylephrine 10% and intracameral lidocaine 1% in phacoemulsification cataract surgery. Methods:, We performed a prospective, double-masked, randomized trial including 20 patients with age-related cataract, who were scheduled for unilateral phacoemulsification and intraocular lens (IOL) implantation. Patients were given either two drops of phenylephrine 10% at 30 mins and 15 mins prior to surgery (group 1), or two drops each of cyclopentolate 1% and phenylephrine 10% at the same time points (group 2). All patients were also given lidocaine 1% intracamerally at the beginning of the procedure. Intraoperative pupil sizes were assessed from video-recordings. Results:, Initially, pupil sizes were significantly smaller in group 1 (4.8 ± 1.2 mm versus 6.5 ± 1.4 mm; p = 0.0098), but the lidocaine injection increased the pupil sizes in group 1 significantly, so that pupil sizes in both groups were equalized throughout the surgical procedure. Conclusions:, Preoperative topical cyclopentolate does not enhance mydriasis in phacoemulsification surgery when using intracameral lidocaine and can be omitted when intracameral lidocaine is used. [source] Thiopental pharmacokinetics in newborn infants: a case report of overdoseACTA PAEDIATRICA, Issue 10 2009Elisabeth Norman Abstract Thiopental may be used for sedation before intubation in newborn infants. A boy, born at 33 weeks of gestation (gw); birth weight 2435 g, was prescribed thiopental 3 mg/kg before intubation. He developed temporary hypotension and oxygen desaturation, and remained unconscious for longer than expected with a suppressed electroencephalography for 48 h. Serum thiopental concentration was 82, 59, 42 and 32 ,mol/L after 20 min and 6, 24 and 68 h respectively. Serum concentrations from five newborn infants at the same time points after intubation with the same thiopental dose were used as reference values, and indicated a 10-fold overdose in the index case. The cause of the overdose could not be identified. The infant recovered; cerebral magnetic resonance imaging at the age of 42 gw and psychomotor development at 2 years were normal. These results show that thiopental concentrations are variable in neonates and there is a high risk of dosage error as no specific paediatric formulation is available. Conclusion:, Well-designed procedures and continuous education are required to prevent errors and adverse events during drug delivery to newborn infants. To develop a safe method of administration for thiopental, an extended pharmacokinetic and pharmacodynamic study in neonates is warranted. [source] Surgical debulking of pituitary macroadenomas causing acromegaly improves control by lanreotideCLINICAL ENDOCRINOLOGY, Issue 6 2008N. Karavitaki Summary Background, Macroadenomas causing acromegaly are cured surgically in only around 50% of patients. Primary medical treatment with somatostatin analogues has been suggested to be a means of treating patients with a potentially poor surgical outcome. Previous retrospective studies have also suggested that surgical debulking of pituitary tumours causing acromegaly improves control by somatostatin analogues. No prospective study using lanreotide has been carried out thus far to assess whether this is the case. Objective, We carried out a prospective study to assess whether surgical debulking of pituitary macroadenomas causing acromegaly improved the subsequent control of acromegaly by the somatostatin analogue lanreotide. Patients and methods, We treated 26 consecutive patients [10 males and 16 females , median age 53·5 years (range 22,70)] with macroadenoma causing acromegaly unselected for somatostatin response for 16 weeks with lanreotide, maximizing GH and IGF-I suppression, if necessary, by incremental dosing. Surgical resection was carried out and the patients were re-assessed off medical treatment at 16 weeks following surgery. Those with nadir GH > 2 mU/l in the oral glucose tolerance test (OGTT) and a mean GH in the GH day curve (GHDC) > 5 mU/l were subsequently restarted on lanreotide and the responses were assessed at the same time points as during the preoperative lanreotide treatment. Results, GH values fell on lanreotide treatment and prior to surgery they were considered ,safe' (mean GH in GHDC < 5 mU/l) in eight patients (30·7%). After surgery, they were ,safe' in 18 patients (69·2%). The figures for normal IGF-I were 11 (42·3%) before surgery and 23 (88·5%) after surgery. After surgery, six patients had nadir GH > 2 mU/l in the OGTT and ,unsafe' GH levels (mean GH in GHDC > 5 mU/l); on re-exposure to lanreotide, GH levels fell in all patients and at the end of 16 weeks postsurgery, they were ,safe' in three of them (50%) (P < 0·05). Pituitary tumour volume was also assessed prospectively, preoperatively on lanreotide and showed a mean fall of 33·1%. Eighty-three percent of patients had > 20% shrinkage. Conclusions, In this first prospective study using lanreotide, surgical debulking of pituitary tumours causing acromegaly improved subsequent postoperative control by the somatostatin analogue lanreotide. Surgery should, therefore, be considered in patients with macroadenoma causing acromegaly, even if there is little prospect of surgical cure. Lanreotide causes significant pituitary tumour shrinkage in the majority of patients. [source] | |||||||||||||