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- Intrapartum magnesium sulfate and need for intensive delivery room resuscitation. [JOURNAL ARTICLE]
- Arch Dis Child Fetal Neonatal Ed 2014 Sep 17.
To evaluate the association of intrapartum magnesium sulfate for fetal neuroprotection (MgSO4-FN) with the delivery room resuscitation and neonatal outcomes of preterm infants in an era of minimisation of invasive mechanical ventilation.Retrospective cohort study.Neonatal intensive care units in the Canadian Neonatal Network.Preterm infants (23(0) to 31(6) weeks gestational age) born in 2011 or 2012. Resuscitation requirements and neonatal outcomes were compared between infants exposed and unexposed to intrapartum MgSO4-FN.The primary outcome was a composite outcome of 'intensive resuscitation', defined as the need for intubation and ventilation or chest compressions or epinephrine administration in the delivery room. Secondary outcomes included mortality and major neonatal morbidities.Of 6015 eligible infants, 1387 (23.1%) were exposed to intrapartum MgSO4-FN. Significantly fewer MgSO4-FN infants (41.0% vs 44.6%, p=0.02) required intensive resuscitation. However, after adjustment for confounders, this difference was no longer significant (adjusted OR (AOR) 0.88; 95% CI 0.66 to 1.17). Infants exposed to MgSO4-FN had decreased odds of death (AOR 0.61; 95% CI 0.40 to 0.94), but there was no difference in neonatal morbidities compared with the unexposed infants.Intrapartum MgSO4 for fetal neuroprotection was not associated with an increased need for intensive delivery room resuscitation in this cohort of preterm infants.
- Effect of Topical Nonsteroidal Anti-Inflammatory Drugs and Nuclear Hardness on Maintenance of Mydriasis During Phacoemulsification Surgery. [JOURNAL ARTICLE]
- J Ocul Pharmacol Ther 2014 Sep 17.
Abstract Purpose: To compare the effects of topical nonsteroidal anti-inflammatory drugs on pupil dilation maintenance during phacoemulsification cataract surgery and quantify the relationships between pupil size change and nuclear hardness. Methods: This prospective randomized clinical observation study was single centered and double-masked. We studied 239 cases undergoing uneventful phacoemulsification cataract surgery in the absence of significant ocular comorbidity. Cases were randomly assigned to 1 of 6 groups receiving the following treatments: (1) diclofenac (0.1%); (2) pranoprofen (0.1%); (3) control, physiological normal saline solution; (4) diclofenac (0.1%) and epinephrine; (5) pranoprofen (0.1%) and epinephrine; (6) control, physiological normal saline and epinephrine solutions. Pupil diameter was measured at 3 intervals of cataract surgery: before the first incision, at the end of nucleus fragmentation, and at the end of cortex irrigation/aspiration. Results: Compared with patients who were not treated, there was a significant difference in maintaining pupil dilation throughout the operation when the patients were treated with either diclofenac or pranoprofen, P<0.001 and P<0.03, respectively. From the first incision to postnucleus fragmentation, the change in pupil size in both diclofenac and control groups was significantly associated with the hardness of the crystalline lens, P=0.001 and P=0.012, respectively. At the end of irrigation/aspiration, the change in pupil size in only the control groups was significantly associated with the hardness of the crystalline lens, P=0.022. Diclofenac treatment was most effective at inhibiting pupil miosis when the hardness of the nucleus was grade 3, P=0.009. Pupil miosis was not related to the hardness of the nucleus when the patients were treated with epinephrine. Conclusions: Both diclofenac and pranoprofen treatment inhibit surgical-induced miosis. There is a negative correlation between the hardness of the crystalline lens and pupil diameter maintenance at the early stage of phacoemulsification.
- Computational Study of Human Tyrosine Hydroxylase Mutants to Uphold [4-(Propan-2-yl) Phenyl]Carbamic Acid as a Potential Inhibitor. [JOURNAL ARTICLE]
- CNS Neurol Disord Drug Targets 2014 Sep 17.
Neurodegenerative diseases that afflict nervous system are characterized by progressive nervous system dysfunction and associated with the one-set of many diseases like Segawa's syndrome (recessive form), autosomal recessive L-dopa-responsive dystonia, L-dopa non-responsive dystonia or progressive early-onset encephalopathy and recessive L-dopa-responsive parkinsonism. It has been reported that number of mutations in coding regions, splice sites and promoter regions of tyrosine hydroxylase (TH) are associated with many such diseases. TH is responsible for catalyzing the conversion of L-tyrosine to L-3,4-dihydroxyphenylalanine. This reaction is considered as rate-limiting step in the biosynthesis of catecholamines, dopamine, norepinephrine and epinephrine, which has made TH an important target for drug development. In our previous study using comparative molecular docking approach, it was concluded that [4-(Propan-2-yl) Phenyl]Carbamic acid (PPCA) may serve as a potential inhibitor. By further extending, our focus is to determine the binding affinities of PPCA and mutated TH. 3D structures of mutated TH were predicted and subjected to molecular docking studies. PPCA was found to bind in the deep narrow groove lined with polar and aromatic amino acids in 14 out of 17 mutants under study (R202H, L205P, H215Y, G216S, T245P, F278P, T283M, R297W, R306H, C328F, A345V, L356M, T368M, Q381K, P461L, T463M and D467G). Our results corroborate efficient binding of PPCA with normal and mutated TH, indicating that PPCA is a strong therapeutic candidate for the treatment of Parkinson's disease and other related disorders. It may be a valuable target for evaluation in preclinical models.
- Nonvariceal upper gastrointestinal bleeding. [JOURNAL ARTICLE]
- Curr Opin Gastroenterol 2014 Sep 16.
Acute upper gastrointestinal bleeding is one of the most common medical emergencies. It is important to recognize potential etiologies of upper gastrointestinal bleeding and understand therapeutic modalities available in achieving hemostasis. This article summarizes guidelines in management of acute nonvariceal upper gastrointestinal bleeding and reviews recent advances in the field.Recent study showed that patients who received blood transfusion with threshold hemoglobin below 7 g/dl rather than below 9 g/dl had significantly lower mortality at 45 days. Endoscopic therapy should be performed on actively bleeding ulcers and ulcers with visible vessel or adherent clot. An over-the-scope clip is a novel device that can be used to achieve hemostasis. It may be a useful tool for achieving hemostasis for patients who failed endoscopic therapy with epinephrine injection, clip, or thermal therapy. Doppler ultrasound probe can evaluate arterial flow to the ulcer and identify ulcers that are at high risk of rebleeding.Upper gastrointestinal bleeding from peptic ulcer disease is not a new clinical problem. Yet, the approach to management continues to evolve with the accumulation of data and well designed studies on the subject.
- Cyanoacrylate spray as treatment in difficult-to-manage gastrointestinal bleeding. [Journal Article]
- World J Gastrointest Endosc 2014 Sep 16; 6(9):448-52.
Gastrointestinal bleeding can be a life-treating event that is managed with standard endoscopic therapy in the majority of cases. However, up to 5%-10% of patients may have persistent bleeding that does not respond to conventional measures. Several endoscopic treatment techniques have been proposed as strategies to control such cases, such as epinephrine injection, hemoclips or argon plasma coagulation, but there are certain clinical scenarios where it is difficult to achieve hemostasis even though adequate use of the available resources is made. Reasons for these failures can be associated with the lesion features, such as extent or location. The use of long-standing techniques in non-traditional scenarios, such as with cyanoacrylate for gastric varices sclerosis, has been reported with favorable results. Although new products such as TC-325 or Ankaferd Blood Stopper hemosprays may be useful, their formulations are not available worldwide. Here we present two clinical cases with very different scenarios of gastrointestinal bleeding, where the use of cyanoacrylate in spray had favorable results in uncommon indications. Cyanoacrylate used as a spray is a technique that can be used as an alternative method in emergent settings.
- Development and validation of a specific and sensitive LC-MS/MS method for quantification of urinary catecholamines and application in biological variation studies. [JOURNAL ARTICLE]
- Anal Bioanal Chem 2014 Sep 17.
Catecholamines are a class of biogenic amines that play an important role as neurotransmitters and hormones. We developed and validated a rapid, specific and sensitive LC-MS/MS method for quantitative determination of catecholamines in human urine. Linearity, specificity, sensitivity, precision, accuracy, matrix effect, carryover, analyte stability, method comparison and reference range were evaluated. The catecholamine measurements were not affected by 35 structurally-related drugs and metabolites. The outstanding specificity was achieved by use of a specific diphenylborate-based solid phase extraction and subsequent selective LC-MS/MS analysis. Excellent sensitivity, accuracy and precision (average intra-assay variations <2.9 % and inter-assay variations <4.6 %) were obtained. The method was successfully applied in the study of day-to-day biological within- and between-subject variations of 25 healthy people under free-living conditions over three consecutive days. We observed that catecholamine excretions for second morning sampling had least day-to-day within-subject variation and excellent reproducibility. This work is one of the rare studies on these topics and represents the first utilization of advanced LC-MS/MS technology. Additionally, we found significant correlations between spot and conventional 24 h collections of human urine (n = 22, r > 0.853, p < 0.0001). These findings suggest that determining the catecholamine concentrations in the second morning urine sample presents accurate, convenient and reliable measurement of catecholamine excretions. In addition, consistent and significant diurnal variations for norepinephrine and epinephrine excretions were observed during the three-day period, while dopamine did not exhibit a diurnal rhythm. The LC-MS/MS method presented here is rapid, sensitive and specific, which could be an advantage in clinical laboratories.
- Changes in platelet morphology and function during 24 hours of storage. [JOURNAL ARTICLE]
- Clin Hemorheol Microcirc 2014 Sep 16.
For in vitro studies assessing the interaction of platelets with implant materials, common and standardized protocols for the preparation of platelet rich plasma (PRP) are lacking, which may lead to non-matching results due to the diversity of applied protocols. Particularly, the aging of platelets during prolonged preparation and storage times is discussed to lead to an underestimation of the material thrombogenicity. Here we study the influence of whole blood- and PRP-storage times on changes in platelet morphology and function. Blood from apparently healthy subjects was collected according to a standardized protocol and examined immediately after blood collection, four hours and twenty four hours later. The capability of platelets to adhere and form stable aggregates (PFA100, closure time) was examined in sodium citrate anticoagulated WB using the agonists equine type I collagen and epinephrine bitartrate (collagen/epinephrine) as well as equine type I collagen and adenosine-5'-diphosphate (collagen/ADP). Circulating platelets were quantified at each time point. Morphology of platelets and platelet aggregates were visualized microscopically and measured using an electric field multi-channel counting system (CASY). The percentage of activated platelets was assessed by means of P-selectin (CD62P) expression of circulating platelets. Furthermore, platelet factor 4 (PF4) release was measured in platelet poor plasma (PPP) at each time point. Whole blood PFA100 closure times increased after stimulation with collagen/ADP and collagen/epinephrine. Twenty four hours after blood collection, both parameters were prolonged pathologically above the upper limit of the reference range. Numbers of circulating platelets, measured in PRP, decreased after four hours, but no longer after twenty four hours. Mean platelet volumes (MPV) and platelet large cell ratios (P-LCR, 12 fL - 40 fL) decreased over time. Immediately after blood collection, no debris or platelet aggregates could be visualized microscopically. After four hours, first debris and very small aggregates occurred. After 24 hours, platelet aggregates and also debris progressively increased. In accordance to this, the CASY system revealed an increase of platelet aggregates (up to 90 μm diameter) with increasing storage time. The percentage of CD62P positive platelets and PF4 increased significantly with storage time in resting PRP. When soluble ADP was added to stored PRP samples, the number of activatable platelets decreased significantly over storage time. The present study reveals the importance of a consequent standardization in the preparation of WB and PRP. Platelet morphology and function, particularly platelet reactivity to adherent or soluble agonists in their surrounding milieu, changed rapidly outside the vascular system. This knowledge is of crucial interest, particularly in the field of biomaterial development for cardiovascular applications, and may help to define common standards in the in vitro hemocompatibility testing of biomaterials.
- Associations between endotoxin-induced metabolic changes and temperament in Brahman bulls. [Journal Article]
- J Anim Physiol Anim Nutr (Berl) 2014 Feb; 98(1):178-90.
The influence of temperament on the alteration of metabolic parameters in response to a lipopolysaccharide(LPS) challenge was investigated. Brahman bulls were selected based on temperament score. Bulls (10 months; 211±5kg BW; n = 6, 8 and 7 for Calm, Intermediate and Temperamental groups, respectively) were fitted with indwelling jugular catheters to evaluate peripheral blood concentrations of glucose, blood urea nitrogen (BUN),non-esterified fatty acids (NEFA), insulin, epinephrine and cortisol before and after LPS administration (0.5 μg/kg BW LPS). Feed intake was also recorded. Intermediate bulls consumed more feed than the Temperamental bulls during the challenge (p = 0.046). Pre-LPS glucose (p = 0.401) and BUN (p = 0.222) did not differ among the temperament groups. However, pre-LPS insulin (p = 0.023) was lower, whereas pre-LPS NEFA (p < 0.001),cortisol (p < 0.001) and epinephrine (p < 0.001) were greater in Temperamental than in Calm and Intermediate bulls. Post-LPS glucose was increased in Calm and Intermediate bulls but not in Temperamental bulls(p < 0.001). Insulin concentrations post-LPS were greater in Calm than in Intermediate and Temperamental bulls (p < 0.001). Concentrations of NEFA post-LPS were greater in Temperamental than in Calm and Intermediate bulls (p < 0.001). Serum BUN concentration increased post-LPS, with values being greater in Calm and Intermediate than in Temperamental bulls (p = 0.012). Collectively, these data demonstrate that animal temperament is related to the metabolic responses of Brahman bulls following a provocative endotoxin challenge.Specifically, Temperamental bulls may preferentially utilize an alternate energy source (i.e. NEFA) to a greater degree than do bulls of Calm and Intermediate temperaments. The use of circulating NEFA from lipolysis may reduce the negative metabolic consequences of an immune response by allowing for a prompt answer to increasing energy demands required during immunological challenge, compared with the time required for glycogenolysis and gluconeogenesis.
- [Levator muscle gravis following injection of lidocaine: a case report]. [English Abstract, Journal Article]
- Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi 2014 Jun; 28(11):829-30.
An allergic reaction was occurred in a 17-years old girl who was undergoing local anesthesia before tonsillectomy. Ptosis was observed in right side of patient shortly after injection of lidocaine to right palate. Then the patient feel grasp and cough, accompanied by nausea and vomiting. The patient was placed in supine position. Dexamethasone and epinephrine was administrated intramuscularly, symptoms were relieved 10 minutes later.
- Anesthetic Comparisons of 4% Concentrations of Articaine, Lidocaine, and Prilocaine as Primary Buccal Infiltrations of the Mandibular First Molar: A Prospective Randomized, Double-blind Study. [JOURNAL ARTICLE]
- J Endod 2014 Sep 10.
Studies have shown the superiority of 4% articaine with 1:100,000 epinephrine over 2% lidocaine with 1:100,000 epinephrine when used as a primary buccal infiltration of the mandibular first molar. A study using other 4% anesthetic formulations may help determine the role of concentration in the increased efficacy of 4% articaine. The authors conducted a prospective randomized, double-blind, crossover study comparing the pulpal anesthesia obtained with 4% concentrations of articaine, lidocaine, and prilocaine formulations as primary buccal infiltrations of the mandibular first molar.Sixty asymptomatic adult subjects randomly received a primary mandibular buccal first molar infiltration of 1.8 mL 4% articaine with 1:100,000 epinephrine, 4% lidocaine with 1:100,000 epinephrine, and 4% prilocaine with 1:200,000 epinephrine in 3 separate appointments. An electric pulp tester was used to test the first molar for anesthesia in 3-minute cycles for 60 minutes after the infiltrations. Successful anesthesia was defined as 2 consecutive 80/80 readings.The success rate for the 4% articaine formulation was 55%, 33% for the 4% lidocaine formulation, and 32% for the 4% prilocaine formulation. There was a significant difference between articaine and both lidocaine (P = .0071) and prilocaine (P = .0187) formulations.A 4% articaine formulation was statistically better than both 4% lidocaine and 4% prilocaine formulations for buccal infiltration of the mandibular first molar in asymptomatic mandibular first molars. However, the success rate of 55% is not high enough to support its use as a primary buccal infiltration technique in the mandibular first molar.