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Intramuscular
Terms modified by Intramuscular Selected AbstractsMotor units in cranial and caudal regions of the upper trapezius muscle have different discharge rates during brief static contractionsACTA PHYSIOLOGICA, Issue 4 2008D. Falla Abstract Aim:, To compare the discharge patterns of motor unit populations from different locations within the upper trapezius muscle during brief submaximal constant-force contractions. Methods:, Intramuscular and surface electromyographic (EMG) signals were collected from three sites of the right upper trapezius muscle distributed along the cranial-caudal direction in 11 volunteers during 10 s shoulder abduction at 25% of the maximum voluntary force. Results:, A total of 38 motor units were identified at the cranial location, 36 from the middle location and 17 from the caudal location. Initial discharge rate was greatest at the caudal location (P < 0.05; mean ± SD, cranial: 16.7 ± 3.6 pps, middle: 16.9 ± 4.0 pps, caudal: 19.2 ± 3.3 pps). Discharge rate decreased during the contraction for the most caudal location only (P < 0.05). Initial estimates of surface EMG root mean square values were highest at the most caudal location (P < 0.05; cranial: 32.3 ± 20.9 ,V, middle: 41.3 ± 21.0 ,V, caudal: 51.6 ± 23.6 ,V). Conclusion:, This study demonstrates non-uniformity of motor unit discharge within the upper trapezius muscle during a brief submaximal constant-force contraction. Location-dependent modulation of discharge rate may reflect spatial dependency in the control of motor units necessary for the development and maintenance of force output. [source] Intramuscular SP1017-formulated DNA electrotransfer enhances transgene expression and distributes hHGF to different rat tissuesTHE JOURNAL OF GENE MEDICINE, Issue 1 2004Marta Riera Abstract Background The systemic administration of a therapeutic protein is a common approach for the treatment of multiple disorders. Intramuscular (i.m.) injection of plasmids, followed by electroporation, has been shown to facilitate naked DNA gene transfer in skeletal muscle allowing proteins to be produced and secreted at therapeutically relevant levels. Methods Plasmid DNA, unformulated or formulated with the non-ionic carrier SP1017, was injected at the rat tibialis anterior muscle followed by the application of electric pulses. Follow-up of protein expression was measured. Results In our study we report that the non-ionic carrier SP1017 significantly increases transgene expression in rat muscle after the i.m. injection of a formulated-pCMV, plasmid followed by electroporation. Such increased expression was observed after delivering square-wave unipolar electric pulses at two different field strengths: low (110 V/cm) and high (175 V/cm). Moreover, elevated secreted placental alkaline phosphatase (SEAP) plasma levels were achieved with low-voltage (110 V/cm) electroporation. Our results also show that human hepatocyte growth factor (hHGF) can be produced from rat muscle and delivered to blood circulation at a biologically active level after a single i.m. injection of an SP1017-formulated plasmid (pCMV/hHGF) followed by electroporation. Tissue distribution studies mostly identified hHGF in the liver, but it was also found in the kidneys and lungs suggesting that here too the HGF could be of therapeutic benefit. Conclusions Our results indicate that SP1017 enhances the expression of electrotransferred genes. Such a delivery approach could prove an efficient method for the systemic production of therapeutic proteins. Copyright © 2003 John Wiley & Sons, Ltd. [source] Sustained delivery of therapeutic concentrations of human clotting factor IX , a comparison of adenoviral and AAV vectors administered in uteroTHE JOURNAL OF GENE MEDICINE, Issue 1 2002Holm Schneider Abstract Background Prenatal somatic gene therapy has been considered for genetic disorders presenting with morbidity at birth. Haemophilia is associated with an increased risk of catastrophic perinatal bleeding complications such as intracranial haemorrhage, which could be prevented by gene transfer in utero. Prenatal gene therapy may be more promising than postnatal treatment, as the fetus may be more amenable to uptake and integration of therapeutic DNA and the immaturity of its immune system may permit life-long immune tolerance of the transgenic protein, thus avoiding the dominant problem in haemophilia treatment, the formation of inhibitory antibodies. Methods Adenovirus serotype 5-derived or AAV serotype 2-derived vectors carrying human clotting factor IX (hfIX) cDNA or a reporter gene were administered intramuscularly, intraperitoneally or intravascularly to late-gestation mouse fetuses. Both vector types were evaluated with respect to the kinetics of hfIX delivery to the systemic circulation and possible immune responses against the vector or the transgene product. Results Mice treated in utero by intramuscular injection of an adenoviral vector carrying hfIX cDNA exhibited high-level gene expression at birth and therapeutic , albeit continuously decreasing , plasma concentrations of hfIX over the entire 6 months of the study. Adenoviral vector spread to multiple organs was detected by polymerase chain reaction (PCR). Intramuscular, intraperitoneal or intravascular application of AAV vectors carrying hfIX cDNA led to much lower plasma concentrations of hfIX shortly after birth, which appeared to decline during the first month of life but stabilized in some of the mice at detectable levels. No signs of immune responses were found, either against the different viral vectors or against hfIX. Conclusion This study demonstrates for the first time that sustained systemic delivery of a therapeutic protein can be achieved by prenatal gene transfer. It thus shows the feasibility of gene therapy in utero and provides a basis for considering this concept as a preventive therapeutic strategy for haemophilia and perhaps also for other plasma protein deficiencies. Copyright © 2002 John Wiley & Sons, Ltd. [source] Fluctuations in isometric muscle force can be described by one linear projection of low-frequency components of motor unit discharge ratesTHE JOURNAL OF PHYSIOLOGY, Issue 24 2009Francesco Negro The aim of the study was to investigate the relation between linear transformations of motor unit discharge rates and muscle force. Intramuscular (wire electrodes) and high-density surface EMG (13 × 5 electrode grid) were recorded from the abductor digiti minimi muscle of eight healthy men during 60 s contractions at 5%, 7.5% and 10% of the maximal force. Spike trains of a total of 222 motor units were identified from the EMG recordings with decomposition algorithms. Principal component analysis of the smoothed motor unit discharge rates indicated that one component (first common component, FCC) described 44.2 ± 7.5% of the total variability of the smoothed discharge rates when computed over the entire contraction interval and 64.3 ± 10.2% of the variability when computed over 5 s intervals. When the FCC was computed from four or more motor units per contraction, it correlated with the force produced by the muscle (62.7 ± 10.1%) by a greater degree (P < 0.001) than the smoothed discharge rates of individual motor units (41.4 ± 7.8%). The correlation between FCC and the force signal increased up to 71.8 ± 13.1% when the duration and the shape of the smoothing window for discharge rates were similar to the average motor unit twitch force. Moreover, the coefficients of variation (CoV) for the force and for the FCC signal were correlated in all subjects (R2 range = 0.14,0.56; P < 0.05) whereas the CoV for force was correlated to the interspike interval variability in only one subject (R2= 0.12; P < 0.05). Similar results were further obtained from measures on the tibialis anterior muscle of an additional eight subjects during contractions at forces up to 20% of the maximal force (e.g. FCC explained 59.8 ± 11.0% of variability of the smoothed discharge rates). In conclusion, one signal captures most of the underlying variability of the low-frequency components of motor unit discharge rates and explains large part of the fluctuations in the motor output during isometric contractions. [source] Extreme Subcutaneous, Intramuscular and Inhaled Insulin Resistance Treated by Pancreas Transplantation AloneAMERICAN JOURNAL OF TRANSPLANTATION, Issue 1 2010J. R. Sa Diabetes mellitus with resistance to insulin administered subcutaneously or intramuscularly (DRIASM) is a rare syndrome and is usually treated with continuous intravenous insulin infusion. We present here two cases of DRIASM in 16 and 18 years female patients that were submitted to pancreas transplantation alone (PTA). Both were diagnosed with type 1 diabetes as young children and had labile glycemic control with recurrent episodes of diabetic ketoacidosis. They had prolonged periods of hospitalization and complications related to their central venous access. Exocrine and endocrine drainages were in the bladder and systemic, respectively. Both presented immediate graft function. In patient 1, enteric conversion was necessary due to reflux pancreatitis. Patient 2 developed mild postoperative hyperglycemia in spite of having normal pancreas allograft biopsy and that was attributed to her immunosuppressive regimen. Patient 1 died 9 months after PTA from septic shock related to pneumonia. In 8 months of follow-up, Patient 2 presented optimal glycemic control without the use of antidiabetic agents. In conclusion, PTA may be an alternative treatment for DRIASM patients. [source] Laparoscopic management of primary hepatic pregnancyAUSTRALIAN AND NEW ZEALAND JOURNAL OF OBSTETRICS AND GYNAECOLOGY, Issue 1 2010Pui-See CHIN A 30-year-old woman presented with epigastric pain with elevated serum human chorionic gonadotropin level (hCG), absence of intrauterine gestational sac and absence of an abnormal adnexal mass on pelvic ultrasonography. Laparoscopy revealed a ruptured hepatic ectopic pregnancy. This was removed by laparoscopic suctioning and haemostasis secured with Surgicel® FribrillaÔ Absorbable Hemostat. Intramuscular methotrexate was administered post-operatively. Patient recovered uneventfully and serum hCG returned to normal. [source] Pediatric Procedural Sedation with Ketamine: Time to Discharge after Intramuscular versus Intravenous AdministrationACADEMIC EMERGENCY MEDICINE, Issue 2 2009Preeti Ramaswamy MBBS Abstract Objectives:, Ketamine is an attractive agent for pediatric procedural sedation. There are limited data on time to discharge comparing intramuscular (IM) vs. intravenous (IV) ketamine. The authors set out to determine whether IM or IV ketamine leads to quicker discharge from the emergency department (ED) and how side effect profiles compare. Methods:, All patients who had received ketamine IM or IV at a tertiary children's hospital ED during the 3-year study period (2004,2007) were identified. Prospective sedation registry data, retrospective medical records, and administrative data were reviewed for drug dosages, use of additional agents, time of drug administration to discharge, total ED time (triage to discharge), and adverse events. A subgroup analysis for patients requiring five or fewer sutures (short suture group) was performed. Results:, A total of 229 patients were enrolled (60% male) with median age of 2.8 years (IQR =1.8,4.3 years) and median weight of 15.7 kg (range = 8.7,74 kg). Ketamine was most frequently employed for laceration repair (80%) and foreign body removal (9%). Overall, 48% received ketamine IM and 52% received it IV. In the short-suture subgroup, 52% received ketamine IM, while 48% received it IV. Multivariate linear regression analysis determined time from drug administration to patient discharge as 21 minutes shorter for IV compared with IM administration, adjusted for age and number of additional doses (R2 = ,0.35; 95% CI = ,0.5 to ,0.19; p < 0.001). Total time in the ED (triage to discharge) comparing IV versus IM administration, adjusting for age and gender and number of additional doses, was not significantly different (p = 0.16). In the short-suture subgroup, time to discharge from administration was also shorter in the IV ketamine group (R2 = ,0.454; 95%CI = ,0.66 to ,0.25; p < 0.001) but similar for total time in ED (p = 0.16). Overall, adverse events occurred in 35% (95% CI = 27% to 45%) of the IM group and 20% (95% CI = 13% to 28%) of the IV group (p = 0.01). Only one patient required brief bag-mask ventilation. Conclusions:, In this institution, time from drug injection to discharge was shorter in the IV compared to IM ketamine group, both overall and for the short-suture group. However, time from triage to discharge was similar. [source] Imaging studies of biodistribution and kinetics in drug developmentDRUG DEVELOPMENT RESEARCH, Issue 2 2003Marc S. Berridge Abstract Although the intravenous route of administration is rarely used for drugs, it is by far the most common route for PET and SPECT radiotracers. This article discusses the use of planar and tomographic nuclear medicine technologies to image and quantify the distribution of drugs after local administration. In principle, this would include topical dermatologic, otic, ophthalmic, rectal, and vaginal administration, as well as the intramuscular, oral, and inhalation routes, although precedents do not yet exist for all of these. The studies reviewed focus mainly on oral ingestion and oral and nasal inhalation. The use of nondrug tracers for formulations is discussed, principally with planar imaging or SPECT using radionuclides such as 99mTc, as well as PET imaging where the active ingredient of a formulation can be labeled with 11C or sometimes 18F. An example of the latter type is a study of the deposition and kinetics in the lungs and airways of triamcinolone acetonide, an antiinflammatory steroid used for topical treatment of allergic rhinitis and asthma, dispensed from an inhaler. PET has high potential for evaluation of different formulations and delivery devices in the development of topically applied drugs. Drug Dev. Res. 59:208,226, 2003. © 2003 Wiley-Liss, Inc. [source] Randomized controlled trial comparing the effectiveness and safety of intranasal and intramuscular naloxone for the treatment of suspected heroin overdoseADDICTION, Issue 12 2009Debra Kerr ABSTRACT Aims Traditionally, the opiate antagonist naloxone has been administered parenterally; however, intranasal (i.n.) administration has the potential to reduce the risk of needlestick injury. This is important when working with populations known to have a high prevalence of blood-borne viruses. Preliminary research suggests that i.n. administration might be effective, but suboptimal naloxone solutions were used. This study compared the effectiveness of concentrated (2 mg/ml) i.n. naloxone to intramuscular (i.m.) naloxone for suspected opiate overdose. Methods This randomized controlled trial included patients treated for suspected opiate overdose in the pre-hospital setting. Patients received 2 mg of either i.n. or i.m. naloxone. The primary outcome was the proportion of patients who responded within 10 minutes of naloxone treatment. Secondary outcomes included time to adequate response and requirement for supplementary naloxone. Data were analysed using multivariate statistical techniques. Results A total of 172 patients were enrolled into the study. Median age was 29 years and 74% were male. Rates of response within 10 minutes were similar: i.n. naloxone (60/83, 72.3%) compared with i.m. naloxone (69/89, 77.5%) [difference: ,5.2%, 95% confidence interval (CI) ,18.2 to 7.7]. No difference was observed in mean response time (i.n.: 8.0, i.m.: 7.9 minutes; difference 0.1, 95% CI ,1.3 to 1.5). Supplementary naloxone was administered to fewer patients who received i.m. naloxone (i.n.: 18.1%; i.m.: 4.5%) (difference: 13.6%, 95% CI 4.2,22.9). Conclusions Concentrated intranasal naloxone reversed heroin overdose successfully in 82% of patients. Time to adequate response was the same for both routes, suggesting that the i.n. route of administration is of similar effectiveness to the i.m. route as a first-line treatment for heroin overdose. [source] Original Article: Pulmonary function, airway cytology and bronchoalveolar lavage fluid drug concentration after aerosol administration of cefquinome to horsesEQUINE VETERINARY EDUCATION, Issue 9 2010T. Art Summary The administration of antibiotics by aerosol to horses suffering from respiratory infections may partially circumvent the limitations of antimicrobial therapy, e.g. large injection volumes, low bioavailability and risk of diarrhoea. Only injectable formulations are available currently and usually contain other substances that could irritate the mucosa and induce coughing and bronchospasm. In addition, the quality of the aerosol, particularly in terms of the delivery of antibiotics to the deep parts of the lung, is unknown. Although used under field conditions, cefquinome delivered by aerosol has never been studied in horses. This study examined the safety of cefquinome injectable solution, administered by aerosol at a dose of 225 mg/inhalation to 7 healthy horses, by assessing (1) pulmonary function before and 15 min after a single inhalation, at the first day (Day 1) and the fifth day (Day 5) of a 5 day period treatment; and (2) the inflammatory status of the lung, i.e. percentage neutrophils and myeloperoxidase concentration, based on bronchoalveolar lavage (BAL) at D1 and D5. In addition, cefquinome concentrations were measured in bronchoalveolar lavage fluid after aerosol, intravenous (i.v.) and intramuscular (i.m.) administrations. A single aerosol of cefquinome injectable solution did not induce any immediate nor delayed pulmonary side effects in healthy horses and produced cefquinome concentrations in bronchoalveolar lavage (BAL) within 30 min that were higher than the minimal inhibitory concentration of the main equine respiratory pathogens. These results should stimulate further studies, especially in horses suffering from bronchial hyper-reactivity. Aerosol delivery of antibiotics may well have a role in equine therapeutics. [source] Quality of life in 1000 patients with early relapsing,remitting multiple sclerosisEUROPEAN JOURNAL OF NEUROLOGY, Issue 6 2009N. Putzki Background and purpose:, To examine the quality of life (QoL) in a large cohort of untreated patients with relapsing,remitting multiple sclerosis (RRMS) and to investigate the impact of intramuscular (IM) interferon beta-1a (IFNß-1a) treatment. Methods:, Prospective, observational, open-label, multicentre study conducted in Germany. Untreated patients with RRMS who initiated treatment with IM IFNß-1a were included and followed for 12 months. QoL was measured using the EQ-5D questionnaire. Clinical response was assessed by relapse rate and disability (Expanded Disability Status Scale; EDSS). Results:, A total of 1157 patients were included [mean age 37.6 years, median disease duration 13 months, mean relapse rate 1.7 (95%CI: 1.58,1.73), median EDSS score 2.0]. Relapse rate was reduced to 0.6 at 12 months (95%CI: 0.51,0.69, P < 0.0001). EDSS did not change significantly. At baseline, QoL was considerably lower in MS patients compared with the general German population, but was improved after treatment initiation [utilities of EQ-5D: 0.77 (95%CI: 0.75,0.78) vs. 0.75 (95%CI: 0.74,0.76) at baseline, 95%CI for difference: 0.01,0.03, P = 0.0046]. Higher disease activity and inability to work were negative predictors of QoL. 14.7% of patients were incapable of working for MS-related reasons. Conclusions:, Quality of life is considerably impaired in early stages of MS. Treatment initiation with IM IFNß attenuates MS disease activity and improves QoL. Inability to work early during the disease is a major challenge for the social security systems. [source] Nitric oxide synthase inhibition reduces O2 cost of force development and spares high-energy phosphates following contractions in pump-perfused rat hindlimb musclesEXPERIMENTAL PHYSIOLOGY, Issue 3 2006David J. Baker The purpose of the present experiments was to test the hypotheses that: (i) nitric oxide synthase (NOS) inhibition reduces the O2 cost of force development across a range of contractile demands; and (ii) this reduced O2 cost of force development would be reflected in a sparing of intramuscular higher energy phosphates. Rat distal hindlimb muscles were pump perfused in situ and electrically stimulated (200 ms trains with pulses at 100 Hz, each pulse 0.05 ms duration) for 1 min each at 15, 30 and 60 tetani min,1 and for 2 min at 90 tetani min,1 in three groups: 0.01 mm adenosine; 1 mm d -NAME and 0.01 mm adenosine (d -NAME); and 1 mm l -NAME and 0.01 mm adenosine (l -NAME). The gastrocnemius,plantaris,soleus muscle group was freeze clamped post-contractions for metabolite analyses. Force was 19% higher and oxygen uptake was 20% lower with l -NAME versus adenosine, and there was a 35% reduction in /time-integrated tension versus adenosine and 24% versusd -NAME that was independent of contraction frequency. l -NAME treatment produced a 33% sparing of muscle phosphocreatine (PCr), and intramuscular lactate was no different between groups. In contrast, d -NAME reduced force by 30%, by 29% and the O2 cost of force development by 15% compared with adenosine, but had no effect on the degree of intramuscular ATP and PCr depletion. These results show that NOS inhibition improved the metabolic efficiency of force development, either by improving the ATP yield for a given O2 consumption or by reducing the ATP cost of force development. In addition, these effects were independent of contraction frequency. [source] Route of Administration Differentially Affects Fevers Induced by Gram-Negative and Gram-Positive Pyrogens in RabbitsEXPERIMENTAL PHYSIOLOGY, Issue 3 2002T. Cartmell We have investigated the febrile responses of New Zealand White rabbits to a Gram-negative pyrogen (bacterial lipopolysaccharide (LPS) from Salmonella typhosa), commonly associated with systemic infection, and a Gram-positive pyrogen (Staphylococcus aureus), more frequently associated with superficial soft tissue infection, each administered via one of four different routes (intravenous, intramuscular, subcutaneous or intraperitoneal) at each of three different doses (LPS: 0.1, 1 and 10 ,g kg,1; S. aureus: 1.5 × 107, 1.5 × 108 and 1.5 × 109 cell walls kg,1). Intravenous administration of LPS evoked rapid, dose-dependent biphasic fever. Injection of LPS by the other routes also evoked dose-dependent fever. However, these fevers were monophasic, had increased latency of onset, and were of lower amplitude. It is important to note that a dose of approximately 10 and 100 times that of the standard intravenous dose was required to produce a similar peak rise in temperature when administered subcutaneously and intraperitoneally, respectively. Intravenous injection of the highest dose of S. aureus evoked dose-dependent biphasic fever, with short latency of onset, which was very similar to that induced by intravenous LPS. At lower doses, intravenous S. aureus induced monophasic fever. No fever occurred when the same doses of S. aureus were administered by any other route. We conclude that any of the four routes may be used for the study of LPS-induced fever, provided that the doses are adjusted. However, studies of S. aureus -induced fever, and detection of contamination with either pyrogen, requires intravenous injection. [source] Comparison of Routes of Flumazenil Administration to Reverse Midazolam-induced Respiratory Depression in a Canine ModelACADEMIC EMERGENCY MEDICINE, Issue 5 2000Melanie S. Heniff MD ABSTRACT Objective: To determine whether flumazenil, a drug used to reverse benzodiazepine-induced respiratory depression and approved only for IV use, is effective by alternative routes. Methods: A randomized, controlled, nonblinded, crossover canine trial was performed to evaluate reversal of midazolam-induced respiratory depression by flumazenil when administered by alternative routes. Mongrel dogs were sedated with thiopental 19 mg/kg IV, then tracheally intubated. With the dogs spontaneously breathing, tidal volume, end-tidal CO2, and O2 saturation were observed until a stable baseline was achieved. Incremental doses of midazolam were administered until respiratory depression (30% decline in tidal volume, 10% decrease in O2 saturation, and 15% increase in end-tidal CO2) occurred. Flumazenil was administered by a randomly selected route [0.2 mg followed 1 minute later by 0.3 mg IV, sublingual (SL) or intramuscular (IM); or 1 mg followed 1 minute later by 1.5 mg per rectum (PR)]. Time to return to baseline respiratory functions was recorded ("time to reversal"). Each of 10 dogs was studied using all 4 routes of flumazenil administration with a washout period of at least 7 days. An additional dog served as a control (no flumazenil). Results: The control time to reversal was 1,620 seconds. The IV route was significantly faster (mean 120 ± 24.5 sec) than the other 3 routes (p < 0.005). The SL route was the second fastest (mean 262 ± 94.5 sec), the IM route was the third fastest (mean 310 ± 133.7 sec), and the PR route was the slowest (mean 342 ± 84.4 sec). The SL, IM, and PR routes did not differ significantly from one another. Conclusions: Flumazenil administered by all 4 routes reversed midazolam-induced respiratory depression in a dog model. For the selected dosages used, the IV route was significantly faster than all 3 other routes, and SL was the second fastest. [source] Factor V deficiency: a concise reviewHAEMOPHILIA, Issue 6 2008J. N. HUANG Summary., Factor V (FV; proaccelerin or labile factor) is the plasma cofactor for the prothrombinase complex that activates prothrombin to thrombin. FV deficiency can be caused by mutations in the FV gene or in genes encoding components of a putative cargo receptor that transports FV (and factor VIII) from the endoplasmic reticulum to the Golgi. Because FV is present in platelet ,-granules as well as in plasma, low FV levels are also seen in disorders of platelet granules. Additionally, acquired FV deficiencies can occur in the setting of rheumatologic disorders, malignancies, and antibiotic use and, most frequently, with the use of topical bovine thrombin. FV levels have limited correlation with the risk of bleeding, but overall, FV-deficient patients appear to have a less severe phenotype than patients with haemophilia A or B. The most commonly reported symptoms are bleeding from mucosal surfaces and postoperative haemorrhage. However, haemarthroses and intramuscular and intracranial haemorrhages can also occur. Because no FV-specific concentrate is available, fresh frozen plasma remains the mainstay of treatment. Antifibrinolytics can also provide benefit, especially for mucosal bleeding. In refractory cases, or for patients with inhibitors, prothrombin complex concentrates, recombinant activated FVIIa, and platelet transfusions have been successfully used. Some patients with inhibitors may also require immunosuppression. [source] Adult Emergency Department Patients with Sickle Cell Pain Crisis: A Learning Collaborative Model to Improve Analgesic ManagementACADEMIC EMERGENCY MEDICINE, Issue 4 2010Paula Tanabe PhD Abstract Objectives:, The objectives were to report the baseline (prior to quality improvement interventions) patient and visit characteristics and analgesic management practices for each site participating in an emergency department (ED) sickle cell learning collaborative. Methods:, A prospective, multisite longitudinal cohort study in the context of a learning-collaborative model was performed in three midwestern EDs. Each site formed a multidisciplinary team charged with improving analgesic management for patients with sickle cell disease (SCD). Each team developed a nurse-initiated analgesic protocol for SCD patients (implemented after a baseline data collection period of 3.5 months at one site and 10 months at the other two sites). All sites prospectively enrolled adults with an acute pain crisis and SCD. All medical records for patients meeting study criteria were reviewed. Demographic, health services, and analgesic management data were abstracted, including ED visit frequency data, ED disposition, arrival and discharge pain score, and name and route of initial analgesic administered. Ten interviews per quarter per site were conducted with patients within 14 days of their ED discharge, and subjects were queried about the highest level of pain acceptable at discharge. The primary outcome variable was the time to initial analgesic administration. Variable data were described as means and standard deviations (SDs) or medians and interquartile ranges (IQR) for nonnormal data. Results:, A total of 155 patients met study criteria (median age = 32 years, IQR = 24,40 years) with a total of 701 ED visits. Eighty-six interviews were conducted. Most patients (71.6%) had between one and three visits to the ED during the study period. However, after removing Site 3 from the analysis because of the short data enrollment period (3.5 months), which influenced the mean number of visits for the entire cohort, 52% of patients had between one and three ED visits over 10 months, 21% had four to nine visits, and 27% had between 10 and 67 visits. Fifty-nine percent of patients were discharged home. The median time to initial analgesic for the cohort was 74 minutes (IQR = 48,135 minutes). Differences between choice of analgesic agent and route selected were evident between sites. For the cohort, 680 initial analgesic doses were given (morphine sulfate, 42%; hydromorphone, 46%; meperidine, 4%; morphine sulfate and ibuprofen or ketorolac, 7%) using the following routes: oral (2%), intravenous (67%), subcutaneous (3%), and intramuscular (28%). Patients reported a significantly lower targeted discharge pain score (mean ± SD = 4.19 ± 1.18) compared to the actual documented discharge pain score within 45 minutes of discharge (mean ± SD = 5.77 ± 2.45; mean difference = 1.58, 95% confidence interval = .723 to 2.44, n = 43). Conclusions:, While half of the patients had one to three ED visits during the study period, many patients had more frequent visits. Delays to receiving an initial analgesic were common, and post-ED interviews reveal that sickle cell pain patients are discharged from the ED with higher pain scores than what they perceive as desirable. ACADEMIC EMERGENCY MEDICINE 2010; 17:399,407 © 2010 by the Society for Academic Emergency Medicine [source] Development and Evaluation of a DNA Vaccine Based on Helicobacter pylori urease B: Failure to Prevent Experimental Infection in the Mouse ModelHELICOBACTER, Issue 6 2006Livania Zavala-Spinetti Abstract Background:, The development of a vaccine against Helicobacter pylori has become a priority to prevent major morbidity and mortality associated with this infection. Our goal was to prepare and evaluate a DNA vaccine based on the urease B gene (ureB). Methods:, The ureB gene of H. pylori was amplified and cloned into the eukaryotic expression vector pcDNA3.1/TOPO. Plasmid DNA was purified from transformed Escherichia coli cells and used to immunize mice by the intragastric, intramuscular, intrarectal (40 µg each) and intranasal (16 µg) route, three doses every 2 weeks, with CpG oligodeoxynucleotide (ODN) as adjuvant. Four weeks after the third dose, animals were orally challenged with Helicobacter felis and were sacrificed 6 weeks later. The stomach was stained to detect the presence of infection. Results:, Despite in vitro confirmation of successful cloning and functionality of the ureB gene with expression of a protein morphologically and antigenically identical to urease B, the DNA vaccine did not perform well in vivo. Immunization of mice produced a weak immune response. Overall, intrarectal and intranasal administration seemed more immunogenic than other routes. Protection against challenge was modest and nonsignificant, and slightly better on animals immunized by the intramuscular and intranasal route. Conclusion:, A DNA vaccine based on H. pylori urease B was poorly immunogenic and nonprotective at the conditions evaluated. Higher doses, better adjuvants or a prime-boost approach may circumvent these limitations. [source] A randomized study of adefovir dipivoxil in place of HBIG in combination with lamivudine as post,liver transplantation hepatitis B prophylaxis,HEPATOLOGY, Issue 5 2008Peter W. Angus Prior to effective prophylaxis, liver transplantation for hepatitis B virus (HBV)-related disease was frequently complicated by recurrence, which could be severe and rapidly progressive. Combination hepatitis B immunoglobulin (HBIG) and lamivudine prophylaxis reduces this rate of recurrence to <5% at 5 years; however, HBIG administration is costly and inconvenient. We conducted a multicenter randomized study of adefovir dipivoxil substitution for low-dose intramuscular (IM) HBIG in patients without HBV recurrence at least 12 months posttransplantation for HBV-related disease. Thirty-four patients were randomized, 16 to adefovir (1 patient withdrew consent at 3 months and is not considered in the results) and 18 to continue HBIG. All continued lamivudine. Groups were well matched by age, sex, and time since transplantation (median, 4.5 years), and background virological risk for HBV recurrence (30% of patients in the adefovir group, 24% in the HBIG group having detectable HBV DNA at transplantation). All patients were alive at study completion without recurrence. One patient in the adefovir group became hepatitis B surface antigen,positive at 5 months but was persistently HBV DNA undetectable via polymerase chain reaction (sensitivity 14 IU/mL) over the following 20 months. Median creatinine was not significantly changed over the course of the study in either group. One patient in the adefovir group with a background of diabetic and hypertensive nephropathy (baseline creatinine 150 ,mol/L) developed increased creatinine leading to dose reduction and ultimately cessation of adefovir at 15 months. Yearly cost of combination adefovir/lamivudine prophylaxis was $8,290 versus $13,718 IM HBIG/lamivudine. Conclusion: Compared with combination HBIG plus lamivudine prophylaxis, combination adefovir plus lamivudine provides equivalent protection against recurrent HBV infection but with better tolerability and less cost. (HEPATOLOGY 2008.) [source] Nicolau Syndrome: three cases and reviewINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 11 2006Kelli Luton MD Nicolau Syndrome, also known as livedo-like dermatitis (LLD) or embolia cutis medicamentosa (ECM), is an infrequent complication following intramuscular and intra-articular injection of various drugs. This rare entity is characterized by severe pain and erythematous-ecchymotic reticular lesions at the injection site, which in many cases lead to necrotic ulcers and scarring. We report three cases of Nicolau Syndrome following injection of diclofenac, penicillin G, and cyanocobalamin. [source] Current hematological findings in cobalamin deficiency.INTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, Issue 1 2006A study of 201 consecutive patients with documented cobalamin deficiency Summary With the introduction of automated assays for measuring serum cobalamin levels over the last decades, the hematological manifestations related to cobalamin deficiency have been changed from the description reported in ,old' studies or textbooks. We studied the hematological manifestations or abnormalities in 201 patients (median age: 67 ± 6 years) with well-documented cobalamin deficiency (mean serum vitamin B12 levels 125 ± 47 pg/ml) extracted from an observational cohort study (1995,2003). Assessment included clinical features, blood count and morphological review. Hematological abnormalities were reported in at least two-third of the patients: anemia (37%), leukopenia (13.9%), thrombopenia (9.9%), macrocytosis (54%) and hypegmented neutrophils (32%). The mean hemoglobin level was 10.3 ± 0.4 g/dl and the mean erythrocyte cell volume 98.9 ± 25.6 fl. Approximately 10% of the patients have life-threatening hematological manifestations with documented symptomatic pancytopenia (5%), ,pseudo' thrombotic microangiopathy (Moschkowitz; 2.5%), severe anemia (defined as Hb levels <6 g/dl; 2.5%) and hemolytic anemia (1.5%). Correction of the hematological abnormalities was achieved in at least two-thirds of the patients, equally well in patients treated with either intramuscular or oral crystalline cyanocobalamin. This study, based on real data from a single institution with a large number of consecutive patients with well-documented cobalamin deficiency, confirms several ,older' findings that were previously reported before the 1990s in several studies and in textbooks. [source] Ectopic pregnancy in a cesarean section scar treated with intramuscular methotrexate and bilateral uterine artery embolizationJOURNAL OF CLINICAL ULTRASOUND, Issue 2 2008Erin L. Hois BSc Abstract We report a case of an ectopic pregnancy implanted in the myometrium at the site of a scar from a previous cesarean section that presented with vaginal bleeding and was successfully treated with bilateral uterine artery embolization and intramuscular administration of methotrexate. The combination of minimally invasive interventional techniques and medical therapies can preserve fertility. © 2007 Wiley Periodicals, Inc. J Clin Ultrasound, 2008 [source] Characterization of susceptibility and carrier status of burbot, Lota lota (L.), to IHNV, IPNV, Flavobacterium psychrophilum, Aeromonas salmonicida and Renibacterium salmoninarumJOURNAL OF FISH DISEASES, Issue 7 2010M P Polinski Abstract In this study, susceptibility and potential carrier status of burbot, Lota lota, were assessed for five important fish pathogens. Burbot demonstrated susceptibility and elevated mortality following challenge with infectious haematopoietic necrosis virus (IHNV) by immersion and to Aeromonas salmonicida by intraperitoneal (i.p.) injection. IHNV persisted in fish for at least 28 days, whereas A. salmonicida was not re-isolated beyond 17 days post-challenge. In contrast, burbot appeared refractory to Flavobacterium psychrophilum following intramuscular (i.m.) injection and to infectious pancreatic necrosis virus (IPNV) by immersion. However, i.p injection of IPNV resulted in re-isolation of virus from fish for the duration of the 28 day challenge. Renibacterium salmoninarum appeared to induce an asymptomatic carrier state in burbot following i.p. injection, but overt manifestation of disease was not apparent. Viable bacteria persisted in fish for at least 41 days, and bacterial DNA isolated by diagnostic polymerase chain reaction was detected from burbot kidney tissue 90 days after initial exposure. This study is the first to investigate susceptibility of burbot to selected fish pathogens, and this information will aid in efforts to culture and manage this species. [source] Protection against atypical furunculosis in Atlantic halibut, Hippoglossus hippoglossus (L.); comparison of a commercial furunculosis vaccine and an autogenous vaccineJOURNAL OF FISH DISEASES, Issue 6 2003S Gudmundsdóttir Abstract Atlantic halibut, Hippoglossus hippoglossus (L.), was shown to be sensitive to infection by three different isolates of Aeromonas salmonicida ssp. achromogenes in pre-challenge tests using intraperitoneal (i.p.) and intramuscular (i.m.) injections as well as bath challenges. A commercial furunculosis vaccine, Alphaject 1200, and an autogenous vaccine, AAS, based on the challenge strain, induced immune protection as shown in challenge tests 8 weeks post-immunization. The survival rate of vaccinated fish after i.p. challenge was 100%, whereas mortality of control fish was 61%. Employing i.m. challenge, relative percentage survival induced by the furunculosis vaccine and the AAS vaccine was 47 and 44, respectively. Mortality of i.m. injected controls was 68%. Vaccinated fish behaved normally following vaccination but the weight gain was significantly reduced in vaccinated fish 8 weeks post-vaccination compared with control fish receiving phosphate-buffered saline. At the same time, intra-abdominal adhesions were observed in fish injected with either of the two vaccines or adjuvant alone. Antibody response against A. salmonicida ssp. achromogenes was detected in sera from fish receiving either vaccine. [source] The efficacy of orally dosed ketamine and ketamine/medetomidine compared with intramuscular ketamine in rhesus macaques (Macaca mulatta) and the effects of dosing route on haematological stress markersJOURNAL OF MEDICAL PRIMATOLOGY, Issue 3 2008Andrew N Winterborn Abstract Background, This study compared the efficacy of two orally-dosed (PO) anaesthetic regimens for chemical immobilization in rhesus macaques (Macaca mulatta), versus the standard protocol of intramuscular (TM) ketamine. In addition, the effects of dosing route on haematological stress markers were evaluated. Methods, Testing was conducted on 18 chronically housed animals. Animals were trained to accept oral dosing and then randomly assigned to one of three drug regimens: (1) ketamine IM, (2) ketamine PO, (3) Ketamine/medetomidine PO. Sedation levels for each regimen were evaluated. Results, Oral dosing alone was not sufficient to achieve a plane of sedation that allowed for safe handling. Serum cortisol and glucose levels were unchanged across groups, although differences were observed in the leukogram profiles. Conclusion, The oral dosages used in this study fell short in providing adequate sedation for safe handling for routine veterinary procedures. Leukogram profiles indicated that orally dosed animals experienced a higher level of stress. [source] Strategies for Implementing School-Located Influenza Vaccination of Children: A Systematic Literature ReviewJOURNAL OF SCHOOL HEALTH, Issue 4 2010John Cawley PhD BACKGROUND: The Advisory Committee on Immunization Practices (ACIP) recommends influenza vaccinations for all children 6 months to 18 years of age, which includes school-aged children. Influenza immunization programs may benefit schools by reducing absenteeism. METHODS: A systematic literature review of PubMed, PsychLit, and Dissertation Abstracts available as of January 7, 2008, was conducted for school-located vaccinations, using search words "School Health Services" and "Immunization Programs"; limited to "Child" (6-12 years) and "Adolescent" (13-18 years) for PubMed and "mass or universal" and (immuniz* or immunis* or vaccin*) and (school or Child or Adolescen*) for PsychLit and Dissertation Abstracts. Fifty-nine studies met the criteria for review. RESULTS: Strategies such as incentives, education, the design of the consent form, and follow-up can increase parental consent and number of returned forms. Minimizing out-of-pocket cost, offering both the intramuscular (shot) and intranasal (nasal spray) vaccination, and using reminders can increase vaccination coverage among those whose parents consented. Finally, organization, communication, and planning can minimize the logistical challenges. CONCLUSIONS: Schools-based vaccination programs are a promising option for achieving the expanded ACIP recommendation; school-located vaccination programs are feasible and effective. Adhering to lessons from the peer-reviewed scientific literature may help public health officials and schools implement the expanded recommendation to provide the greatest benefit for the lowest cost. Given the potential benefits of the expanded recommendation, both directly to the vaccinated children and indirectly to the community, prospective, well-controlled trials to establish the cost-effectiveness of specific vaccination strategies should be high priorities for future research. [source] Analgesic and antiemetic effect of ketorolac vs. betamethasone or dexamethasone after ambulatory surgeryACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 3 2007K. S. Thagaard Background:, Glucocorticoids are known to provide slower onset and more prolonged duration of analgesic effect than ketorolac. In the present study, we wanted to evaluate the effect over time from a single dose of either intravenous (i.v.) dexamethasone or an intramuscular (i.m.) depot formulation of betamethasone compared with i.v. ketorolac. Materials and methods:, One hundred and seventy-nine patients admitted for mixed ambulatory surgery were included in the study. After induction of general i.v. anaesthesia, the patients were randomized to receive double-blindly either dexamethasone 4 mg i.v. (Group D) or betamethasone depot formulation 12 mg i.m. (Group B) or ketorolac 30 mg i.v. (Group K). Fentanyl was used for rescue analgesic medication in the post-operative care unit (PACU) and codeine with paracetamol after discharge, for a study period of 3 days. Results:, There was significantly less post-operative pain in the ketorolac group during the stay in the unit (88% with minor or less pain in Group K vs. 74% and 67% in Groups D and B, respectively, P < 0.05), significantly less need for rescue medication (P < 0.05) and significantly less nausea or vomiting (12% in Group K vs. 30% in the other groups pooled, P < 0.05). The ketorolac patients were significantly faster for ready discharge, median 165 min vs. 192 min and 203 min in Groups D and B, respectively (P < 0.01). There were no differences between the groups in perceived pain, nausea, vomiting or rescue analgesic consumption in the 4- to 72-h period. Conclusion:, Dexamethasone 4 mg or bethamethasone 12 mg did not provide prolonged post-operative analgesic effect compared with ketorolac 30 mg, which was superior for analgesia and antiemesis in the PACU. [source] Pharmacokinetics and pharmacokinetic/pharmacodynamic integration of orbifloxacin in Korean Hanwoo cattleJOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 3 2009G. ELIAS The pharmacokinetics and pharmacodynamics of orbifloxacin were studied in six clinically healthy Hanwoo cows after intravenous (i.v.) and intramuscular (i.m.) administration at a dose of 3 mg/kg. Orbifloxacin concentrations were determined by high performance liquid chromatography with fluorescence detection. Steady-state volume of distribution and clearance of orbifloxacin after i.v. administration were 0.92 L/kg and 0.24 L/h·kg, respectively. Following i.m. administration, a slow and complete absorption with absolute bioavailability of 101.4%, and a maximum concentration (Cmax) of 1.17 ,g/mL at 1.04 h were observed. The in vitro serum protein binding was 14.76%. The in vitro antibacterial activity of orbifloxacin against a pathogenic strain of Mannheimia haemolytica (M. haemolytica), Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) was determined. The ex vivo activity of orbifloxacin against M. haemolytica strain was also determined, and these data were integrated with the ex vivo bacterial counts to establish AUC24h/MIC values producing bacteriostatic action, bactericidal action and elimination of bacteria. Mean values were 32.7, 51.6 and 102.6 h, respectively. From these data, we predict that orbifloxacin, when administered i.m. at a dosage of 2.5,5 mg/kg once a day, would be effective against bovine pathogens, such as M. haemolytica. Additional studies may be needed to confirm its efficacy in a clinical setting, and to evaluate the penetration of the drug in diseased tissues. [source] Characterization of the pharmacokinetic disposition of levofloxacin in stallions after intravenous and intramuscular administrationJOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2008A. GOUDAH The target of the present study was to investigate the plasma disposition kinetics of levofloxacin in stallions (n = 6) following a single intravenous (i.v.) bolus or intramuscular (i.m.) injection at a dose rate of 4 mg/kg bwt, using a two-phase crossover design with 15 days as an interval period. Plasma samples were collected at appropriate times during a 48-h administration interval, and were analyzed using a microbiological assay method. The plasma levofloxacin disposition was best fitted to a two-compartment open model after i.v. dosing. The half-lives of distribution and elimination were 0.21 ± 0.13 and 2.58 ± 0.51 h, respectively. The volume of distribution at steady-state was 0.81 ± 0.26 L/kg, the total body clearance (Cltot) was 0.21 ± 0.18 L/h/kg, and the areas under the concentration,time curves (AUCs) were 18.79 ± 4.57 ,g.h/mL. Following i.m. administration, the mean t1/2el and AUC values were 2.94 ± 0.78 h and 17.21 ± 4.36 ,g.h/mL. The bioavailability was high (91.76% ± 12.68%), with a peak plasma mean concentration (Cmax) of 2.85 ± 0.89 ,g/mL attained at 1.56 ± 0.71 h (Tmax). The in vitro protein binding percentage was 27.84%. Calculation of efficacy predictors showed that levofloxacin might have a good therapeutic profile against Gram-negative and Gram-positive bacteria, with an MIC , 0.1 ,g/mL. [source] Pharmacokinetics of difloxacin in pigs and broilers following intravenous, intramuscular, and oral single-dose applicationsJOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 3 2008H. Z. DING Pharmacokinetics of difloxacin, a fluoroquinolone antibiotic, was determined in pigs and broilers after intravenous (i.v.), intramuscular (i.m.), or oral (p.o.) administration at a single dose of five (pigs) or 10 mg/kg (broilers). Plasma concentration profiles were analyzed by a compartmental pharmacokinetic method. Following i.v., i.m. and p.o. doses, the elimination half-lives (t1/2,) were 17.14 ± 4.14, 25.79 ± 8.10, 16.67 ± 4.04 (pigs) and 6.11 ± 1.50, 5.64 ± 0.74, 8.20 ± 3.12 h (broilers), respectively. After single i.m. and p.o. administration, difloxacin was rapidly absorbed, with peak plasma concentrations (Cmax) of 1.77 ± 0.66, 2.29 ± 0.85 (pigs) and 2.51 ± 0.36, 1.00 ± 0.21 ,g/mL (broilers) attained at tmax of 1.29 ± 0.26, 1.41 ± 0.88 (pigs) and 0.86 ± 0.4, 4.34 ± 2.40 h (broilers), respectively. Bioavailabilities (F) were (95.3 ± 28.9)% and (105.7 ± 37.1)% (pigs) and (77.0 ± 11.8)% and (54.2 ± 12.6)% (broilers) after i.m. and p.o. doses, respectively. Apparent distribution volumes(Vd(area)) of 4.91 ± 1.88 and 3.10 ± 0.67 L/kg and total body clearances(ClB) of 0.20 ± 0.06 and 0.37 ± 0.10 L/kg/h were determined in pigs and broilers, respectively. Areas under the curve (AUC), the half-lives of both absorption and distribution(t1/2ka, t1/2,) were also determined. Based on the single-dose pharmacokinetic parameters determined, multiple dosage regimens were recommended as: a dosage of 5 mg/kg given intramuscularly every 24 h in pigs, or administered orally every 24 h at the dosage of 10 mg/kg in broilers, can maintain effective plasma concentrations with bacteria infections, in which MIC90 are <0.25 ,g/mL and <0.1 ,g/mL respectively. [source] Pharmacokinetic,pharmacodynamic integration of orbifloxacin in rabbits after intravenous, subcutaneous and intramuscular administrationJOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 1 2008P. MARÍN The single-dose disposition kinetics of orbifloxacin were determined in clinically normal rabbits (n = 6) after intravenous (i.v.), subcutaneous (s.c.) and intramuscular (i.m.) administration of 5 mg/kg bodyweight. Orbifloxacin concentrations were determined by high performance liquid chromatography with fluorescence detection. Minimal inhibitory concentrations (MICs) assay of orbifloxacin against 30 strains of Staphylococcus aureus from several European countries was performed in order to compute pharmacodynamic surrogate markers. The concentration,time data were analysed by compartmental and noncompartmental kinetic methods. Steady-state volume of distribution (Vss) and total body clearance (Cl) of orbifloxacin after i.v. administration were estimated to be 1.71 ± 0.38 L/kg and 0.91 ± 0.20 L/h·kg, respectively. Following s.c. and i.m. administration orbifloxacin achieved maximum plasma concentrations of 2.95 ± 0.82 and 3.24 ± 1.33 mg/L at 0.67 ± 0.20 and 0.65 ± 0.12 h, respectively. The absolute bio-availabilities after s.c. and i.m. routes were 110.67 ± 11.02% and 109.87 ± 8.36%, respectively. Orbifloxacin showed a favourable pharmacokinetic profile in rabbits. However, on account of the low AUC/MIC and Cmax/MIC indices obtained, its use by i.m. and s.c. routes against the S. aureus strains assayed in this study cannot be recommended given the risk of selection of resistant populations. [source] | |||||||||||||||||||||||||||||||||||||