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Ibuprofen sodium salt (IP) was encapsulated in cyclodextrin nanosponges (CDNS) obtained by cross-linking of β-cyclodextrin with ethylenediaminetetraacetic acid dianhydride (EDTAn) in two different preparations: CDNSEDTA 1:4 and 1:8, where the 1:n notation indicates the CD to EDTAn molar ratio. The entrapment of IP was achieved by swelling the two polymers with a 0.27 M solution of IP in D2O, leading to colourless, homogeneous hydrogels loaded with IP. The molecular environment and the transport properties of IP in the hydrogels were studied by high resolution magic angle spinning (HRMAS) NMR spectroscopy. The mean square displacement (MSD) of IP in the gels was obtained by a pulsed field gradient spin echo (PGSE) NMR pulse sequence at different observation times t d. The MSD is proportional to the observation time elevated to a scaling factor α. The α values define the normal Gaussian random motion (α = 1), or the anomalous diffusion (α < 1, subdiffusion, α > 1 superdiffusion). The experimental data here reported point out that IP undergoes subdiffusive regime in CDNSEDTA 1:4, while a slightly superdiffusive behaviour is observed in CDNSEDTA 1:8. The transition between the two dynamic regimes is triggered by the polymer structure. CDNSEDTA 1:4 is characterized by a nanoporous structure able to induce confinement effects on IP, thus causing subdiffusive random motion. CDNSEDTA 1:8 is characterized not only by nanopores, but also by dangling EDTA groups ending with ionized COO(-) groups. The negative potential provided by such groups to the polymer backbone is responsible for the acceleration effects on the IP anion thus leading to the superdiffusive behaviour observed. These results point out that HRMAS NMR spectroscopy is a powerful direct method for the assessment of the transport properties of a drug encapsulated in polymeric scaffolds. The diffusion properties of IP in CDNS can be modulated by suitable polymer synthesis; this finding opens the possibility to design suitable systems for drug delivery with predictable and desired drug release properties.
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These data, together with previously reported findings of a significant decrease in upper gastrointestinal endoscopic ulcer rate at 6 months, support the overall safety, compliance, and tolerability of this single-tablet formulation.
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Endotoxin is a major mediator of the life-threatening cardiovascular dysfunction that characterizes Gram-negative sepsis. In animal models of endotoxemia, pretreatment with ibuprofen or pentoxifylline attenuates some of these cardiovascular changes. To evaluate the effects of these agents on the human cardiovascular response to endotoxemia, hemodynamic variables were measured serially in 24 normal subjects who were given intravenous endotoxin. The subjects were randomized to receive oral ibuprofen (n = 9), pentoxifylline (n = 10), or no medication before endotoxin administration (n = 5). The subjects were volume loaded 3-5 h after endotoxin administration, and hemodynamic measurements were reassessed. Core temperature after endotoxin alone or endotoxin-pentoxifylline approached a maximum at 3 h (greater than or equal to 38.6 degrees C), while the endotoxin-ibuprofen group remained afebrile. At 3 and 5 h, all three groups had significant increases in heart rate, cardiac index, oxygen delivery, and oxygen consumption, while systemic vascular resistance index decreased significantly from baseline. The oxygen extraction ratio remained unchanged. After volume loading, the left ventricular ejection fraction and left ventricular end-diastolic and end-systolic volume indexes did not differ among the groups. The hyperdynamic cardiovascular response to endotoxin in humans occurs in the absence of fever and is not significantly ameliorated by oral cyclooxygenase or phosphodiesterase inhibition.
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We investigated whether chemical association of phosphatidylcholine (PC) to ibuprofen enhances the anti-inflammatory/analgesic activity of the nonsteroidal anti-inflammatory drug (NSAID) and whether any change in therapeutic action is due to alterations in drug bioavailability and cyclooxygenase (COX) inhibitory activity. Acute/chronic joint inflammation was induced in rats, by injection of Complete Freund's Adjuvant. In the acute study, rats were administered saline, ibuprofen, or PC-ibuprofen (at NSAID doses of 10, 25, and 50 mg/kg), and 2 h later the pain threshold of the affected joint to pressure was measured. PC-ibuprofen increased the pain threshold at all NSAID doses, whereas unmodified ibuprofen demonstrated analgesic activity at only the highest dose. In the chronic study, we investigated the effects of saline, PC-ibuprofen, and ibuprofen (administered at 15 and 25 mg/kg/day) on ankle thickness and pain threshold, and demonstrated that PC-ibuprofen had significantly greater anti-inflammatory and analgesic activity than ibuprofen, over a 30- to 60-day period. PC association resulted in reduced uptake (decreased Cmax), a modest increase in the area under the curve, and a longer t(1/2) of ibuprofen. We also demonstrated that PC-ibuprofen was a comparable or a more effective inhibitor of both 6-keto-prostaglandin F1alpha concentration of fluid collected from tissue in and around the inflamed stifle joint, and COX-2 activity in activated human umbilical vein endothelial cells. In conclusion, we have demonstrated that PC association results in increases in ibuprofen's anti-inflammatory and analgesic activity in rodent models of acute and chronic joint inflammation, and this effect may relate to alterations in drug bioavailability and COX-inhibitory potency.
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Prospective, randomized, crossover trial.
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The potential occurrences of endocrine-disrupting compounds (EDCs), as well as pharmaceuticals, are considered to be emerging environmental problems due to their persistence and continuous input into the aquatic ecosystem, even at only trace concentrations. This study systematically investigated the oxidative removal of eight specially selected ECDs and pharmaceuticals by comparing their relative reactivity as a function of different oxidative treatment processes (i.e., free chlorine, ozone, monochloramine, and permanganate) under various pH conditions. For the oxidative removal study, EDC and pharmaceutical standards were spiked into both deionized water and natural water, followed by treatment using common oxidants at typical water treatment concentrations. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used for identification and quantification. The removal efficiency of the EDCs and pharmaceuticals varied significantly between oxidation processes. Free chlorine, permanganate, and ozone treatments were all highly effective at the elimination of triclosan and estrone, while they were not effective for removing ibuprofen, iopromide, and clofibric acid. Monochloramine (at a dose of 3mg/L) was mostly ineffective in eliminating any of the selected EDCs and pharmaceuticals under the tested conditions. pH also played an important role in the removal efficiency of the EDCs and pharmaceuticals during free chlorine, permanganate, and ozone treatments. Additionally, the study identified the oxidation products of triclosan by permanganate, and 2,4-dichlorophenol was identified as the major oxidation product of triclosan by permanganate in drinking water system treatment. Furthermore, 2,4-dichlorophenol was further degradated to 4,5-dichloro-2-(2,4-dichlorophenoxy)phenol and/or 5,6-dichloro-2-(2,4-dichlorophenoxy)phenol. The kinetics for this reaction indicated that the reaction was first order in the drinking water system.
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The European Society for Clinical Microbiology and Infectious Diseases established the Sore Throat Guideline Group to write an updated guideline to diagnose and treat patients with acute sore throat. In diagnosis, Centor clinical scoring system or rapid antigen test can be helpful in targeting antibiotic use. The Centor scoring system can help to identify those patients who have higher likelihood of group A streptococcal infection. In patients with high likelihood of streptococcal infections (e.g. 3-4 Centor criteria) physicians can consider the use of rapid antigen test (RAT). If RAT is performed, throat culture is not necessary after a negative RAT for the diagnosis of group A streptococci. To treat sore throat, either ibuprofen or paracetamol are recommended for relief of acute sore throat symptoms. Zinc gluconate is not recommended to be used in sore throat. There is inconsistent evidence of herbal treatments and acupuncture as treatments for sore throat. Antibiotics should not be used in patients with less severe presentation of sore throat, e.g. 0-2 Centor criteria to relieve symptoms. Modest benefits of antibiotics, which have been observed in patients with 3-4 Centor criteria, have to be weighed against side effects, the effect of antibiotics on microbiota, increased antibacterial resistance, medicalisation and costs. The prevention of suppurative complications is not a specific indication for antibiotic therapy in sore throat. If antibiotics are indicated, penicillin V, twice or three times daily for 10 days is recommended. At the present, there is no evidence enough that indicates shorter treatment length.
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The PAIN (Paracetamol, Aspirin and Ibuprofen New tolerability) study published in 1999 assessed the tolerability of over-the- counter (OTC) analgesics in a French general practitioner (GP)-controlled population and found no apparent difference between the tolerability of ibuprofen and paracetamol (acetaminophen). However, patient selection in that study could cast doubt over the relevance of the results to a more generalised OTC population. The aim of our survey was to prospectively determine what proportion of a French GP-controlled population is able to take ibuprofen and paracetamol in order to allow appropriate interpretation of the PAIN study.
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Sixty-five patients completed the study, 34 receiving TAP block with ropivacaine and 31 receiving sham block with isotonic saline. We found no differences in median (interquartile range) morphine consumption the first 24 h between the TAP block group [17.5 mg (6.9-36.0 mg)] and the placebo group [17.5 mg (2.9-38.0 mg)] (95% confidence interval 10.0-22.6 mg, P = 0.648). No differences were found for VAS scores between the two groups, calculated as area under the curve/1-24 h, neither at rest (P = 0.112) nor while coughing (P = 0.345), or for PONV between groups.
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Six of the 16 studies demonstrated increased risk for one or more NANSAIDs (rate or ORs varied from 1.13 to 3.08). Five studies demonstrated cardioprotective effect for one or more NANSAIDs used (rate or ORs varied from 0.48 to 0.84). None of the other studies demonstrated an association between use of NANSAIDs and risk of cardiovascular events.
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The relative contribution of treated and untreated wastewater in surface water might be assessed by measuring chemical markers. Recalcitrant pharmaceuticals like carbamazepine are suitable as chemical markers for estimating the relative contribution of wastewater in surface water. The easily degradable caffeine might be a good indicator for raw sewage and hardly treated wastewaters.
Copolymers of 2-hydroxyethyl methacrylate (HEMA) and methacrylic acid (MAA) based hydrogels containing 5 and 10% of a cross-linking agent were studied as drug delivery systems. Terephthalic acid was covalently linked with HEMA, abbreviated as CA. Radiation copolymerization of HEMA and MAA, mixed with a particulate glibenclamide with the various ratios CA as crosslinking agent were carried out at the room temperature. The structure of the CA was confirmed by FTIR, H NMR and C NMR spectroscopy. The compositions of the cross-linked three-dimensional polymers were determined by FTIR spectroscopy. Glass transition temperature (T) of the network polymers was determined calorimetrically. The hydrolysis of drug-polymer conjugates was carried out in cellophane membrane dialysis bags containing an aqueous buffer solution (pH 7.4 and pH 1) at 37 degree C. The drug-release profiles indicate that amount drug release depends on their degree of swelling and cross-linking.
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Ibuprofen has a more important effect in limiting adhesion formation compared with rofecoxib after flexor tendon repair. Because ibuprofen inhibits both COX-1 and COX-2, whereas rofecoxib only inhibits COX-2, ibuprofen therapy appears to offer a greater beneficial effect on tendon repair by reducing formation of adhesions.
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We analyzed data on 114 460 women in the California Teachers Study cohort who were aged 22 to 85 years and free of breast cancer at baseline in 1995 to 1996. Information on frequency and duration of NSAID use was collected through a self-administered questionnaire. A total of 2391 women were diagnosed with breast cancer during the follow-up period from 1995 to 2001. We used Cox proportional hazards regression to estimate relative risks (RR) and 95% confidence intervals (CI) of breast cancer subtypes with NSAID use.
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Indomethacin treatment caused a significant decrease in urinary ADH excretion (21.8 +/- 20.8 vs. 13.8 +/- 12.9 pg/ml; p < 0.05), along with a significant reduction in urinary sodium (92.1 +/- 36.1 vs. 64.8 +/- 35.6; p < 0.05), fractional excretion of sodium (68.5 +/- 37.1 vs. 45.6 +/- 37.1; p < 0.05), and urinary osmolality (276.2 +/- 103.9 vs. 226.4 +/- 60.3; p < 0.05). Ibuprofen treatment did not modify urinary ADH excretion and caused a statistically insignificant decrease in urinary sodium and in fractional excretion of sodium.
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In the study reported here, we determined the effects on bone healing of rofecoxib, one of the selective cyclooxygenase-2 (Cox-2) inhibitors that has been used for postsurgical analgesia, and compared these effects with those of nonselective ibuprofen and placebo. Each of 66 male rats received a closed, nondisplaced femoral fracture and was fed rofecoxib, ibuprofen, or placebo for 4 weeks. Results of postsacrifice evaluation showed gross nonunions in 64.7% of rofecoxib rats (P < .0001), 17.6% of ibuprofen rats (P = .007), and 0% of placebo rats. Compared with ibuprofen, rofecoxib was significantly more likely to produce nonunions (P = .007). Mean callus width was 8.9 mm (SD, 1.3 mm) for rofecoxib (P = .03), 8.9 mm (SD, 1.2 mm) for ibuprofen (P = .03), and 8.0 mm (SD, 1.3 mm) for placebo. Mean healing maturity (Goldberg classification) was 1.6 (SD, 0.7) for rofecoxib (P < .0001), 1.7 (SD, 0.8) for ibuprofen (P = .0001), and 2.7 (SD, 0.6) for placebo. Mean fracture angulation was 30.8 degrees (SD, 16.7 degrees) for rofecoxib (P = .003), 14.3 degrees (SD, 14.4 degrees) for ibuprofen (NS), and 13.4 degrees (SD, 10.3 degrees) for placebo. Mean histologic healing was 5.75 for rofecoxib (P = .02), 6.35 for ibuprofen (P = .05), and 8.25 for placebo. Cox-2 inhibitors should be used with caution when bone healing is necessary. Further study is warranted to determine whether the adverse effects occur in humans.
We analyzed data from the prospective Women's Health Initiative (WHI) Observational Study to examine the effects of regular use of aspirin, ibuprofen, and other nonsteroidal anti-inflammatory drugs (NSAIDs) on breast cancer risk. We studied a population of 80,741 postmenopausal women between 50 and 79 years of age who reported no history of breast cancer or other cancers (excluding nonmelanoma skin cancer), and we completed a personal baseline interview that elicited comprehensive health information including data on breast cancer risk factors and NSAID use. All of the cases were adjudicated by WHI physicians using pathology reports. Our analysis was based on 1392 confirmed cases of breast cancer. Relative risks (RRs) with 95% confidence intervals (CIs) were estimated with adjustment for age and other breast cancer risk factors. Regular NSAID use (two or more tablets/week) for 5-9 years produced a 21% reduction in the incidence of breast cancer (RR, 0.79; 95% CI, 0.60-1.04); regular NSAID use for 10 or more years produced a 28% reduction (RR, 0.72; CI, 0.56-0.91), and there was a statistically significant inverse linear trend of breast cancer incidence with the duration of NSAID use (P < 0.01). The estimated risk reduction for long-term use of ibuprofen (RR, 0.51; CI, 0.28-0.96) was greater than for aspirin (RR, 0.79; CI, 0.60-1.03). Subgroup analysis by breast cancer risk factors did not result in effect modification. Regular use of acetaminophen (an analgesic agent with little or no anti-inflammatory activity) or low-dose aspirin (<100 mg) was unrelated to the incidence of breast cancer. Our results indicate that the regular use of aspirin, ibuprofen, or other NSAIDs may have a significant chemopreventive effect against the development of breast cancer and underscore the need for clinical trials to confirm this effect.
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The trend in mortality is worrisome but does not contraindicate an aggressive approach to the clinically significant PDA that has bidirectional flow at the time of the echocardiogram.
The physical measurements of a fluid bed granulator can be exploited in construction of an operating window, a design space, for process performance. The purpose of this study was to determine the influence of inlet air humidity changes on temperature in different parts of a granulator system, on fluidisation behaviour and on the particle size of the final granules. A humidifying setup was constructed on a bench-scale fluid bed granulator that enabled elevated humidity levels and sharp humidity changes of the inlet air. Ibuprofen granules were produced at the various inlet air humidity levels classified as low, intermediate and high. A novel fluidisation parameter was developed. The more improperly the particles were fluidising the smaller was the relationship of airflow rate and fan speed. Four different failure modes were identified and classified, based on the fluidisation parameter: over-fluidisation, risk of improper fluidisation, improper fluidisation and collapsed bed. It was possible to construct process trajectories for smooth fluidisation, which the optimal granulation process should follow.
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The impact of ibuprofen combined with amoxicillin or erythromycin for therapy of penicillin-resistant pneumococcal acute otitis media (AOM) was evaluated in a gerbil model. Ibuprofen (at 2.5 or 7.5 mg/kg, orally) and/or amoxicillin or erythromycin (5 mg/kg each, s.c.) were administered at 5 h (early therapy, as single-dose regimen) or at 18 h (delayed therapy, five doses) postinoculation (PI). Each antibiotic alone and combined with ibuprofen was more effective administered as early regimen than as delayed treatment when evaluating the presence of otorrhea, otoscopic aspect, culture-positive and bacterial counts in middle ear (ME) samples, and loss of body weight. There was a trend for a better bacteriological outcome in animals receiving amoxicillin or erythromycin and ibuprofen, especially with the high dose. Such a dose of ibuprofen, associated with each antibiotic regimen, also preserved the animal well-being, avoiding a great weight loss in comparison to those receiving the antibiotic alone but a statistically significant difference was only observed for animals receiving delayed therapy with erythromycin and high-dose ibuprofen. In conclusion, ibuprofen combined with antibiotics seemed to improve the outcome of this experimental pneumococcal AOM.
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The aim of this study was to clarify the candidate cells for and the mechanism of superoxide anion (O2*-) release into the hepatic sinusoids during short-term exposure to ethanol.
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To compare differences in blood pressure levels between patients with severe post-partum pre-eclampsia using ibuprofen or acetaminophen.
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Because of the complex, multifaceted nature of spinal cord injury (SCI), it is widely believed that a combination of approaches will be superior to individual treatments. Therefore, we employed a rat model of cervical SCI to evaluate the combination of four noninvasive treatments that individually have been reported to be effective for acute SCI during clinically relevant therapeutic time windows. These treatments included ghrelin, ibuprofen, C16, and ketogenic diet (KD). These were selected not only because of their previously reported efficacy in SCI models but also for their potentially different mechanisms of action. The administration of ghrelin, ibuprofen, C16, and KD several hours to days postinjury was based on previous observations by others that each treatment had profound effects on the pathophysiology and functional outcome following SCI. Here we showed that, with the exception of a modest improvement in performance on the Montoya staircase test at 8-10 weeks postinjury, the combinatorial treatment with ghrelin, ibuprofen, C16, and KD did not result in any significant improvements in the rearing test, grooming test, or horizontal ladder. Histologic analysis of the spinal cords did not reveal any significant differences in tissue sparing between treatment and control groups. Although single approaches of ghrelin, ibuprofen, C16, and KD have been reported to be beneficial after SCI, our results show that the combination of the four interventions did not confer significant functional or histological improvements in a cervical model of SCI. Possible interactions among the treatments may have negated their beneficial effects, emphasizing the challenges that have to be addressed when considering combinatorial drug therapies for SCI.
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Hintergrund: Die Durchführung vieler klinischer Studien wird beeinträchtigt durch ungenügenden Patienteneinschluss, nicht zuletzt aufgrund einer nennenswerten Anzahl infrage kommender Patienten, die eine Studienteilnahme ablehnen. Auch wenn Barrieren und motivierende Faktoren für eine Studienteilnahme von Patienten mit onkologischen Erkrankungen oder chronischen Krankheiten bereits untersucht wurden, ist wenig bekannt über die diesbezügliche Einstellung hausärztlicher Patienten, die mit einer unkomplizierten Erkrankung ihren Hausarzt aufsuchen. Die vorliegende Studie hat zum Ziel, Motivationsfaktoren und Barrieren hausärztlicher Patienten für eine Studienteilnahme zu untersuchen, und Faktoren zu identifizieren, die die Patientenrekrutierung in zukünftigen Studien erleichtern. Methode: Diese Studie war eingebettet in eine Arzneimittelstudie, in der zwei Behandlungsstrategien bei Frauen mit unkompliziertem Harnwegsinfekt im hausärztlichen Setting untersucht wurden. Semistrukturierte telefonische Interviews wurden sowohl mit Studienteilnehmerinnen wie auch mit Ablehnerinnen durchgeführt. Der Interviewleitfaden fokussierte auf den persönlichen motivierenden oder hinderlichen Faktoren der Patientinnen. Weitere Aspekte umfassten das Studienthema, die Rolle des Hausarztes, Randomisierung, Studienabläufe und potentielle motivierende/hinderliche Faktoren für andere Patientinnen. Die Analyse der Transskripte erfolgte mittels zusammenfassender qualitativer Inhaltsanalyse.Ergebnisse: 20 Interviews mit Studienteilnehmerinnen und 5 Interviews mit Ablehnerinnen wurden durchgeführt. Die Ergebnisse zeigen unterschiedliche Gründe für eine Studienteilnahme aus den drei Bereichen: persönliche Aspekte, studienbezogene Aspekte und Beziehung zum Hausarzt. Ein relevantes Studienthema und ein wahrgenommener persönlicher Benefit fördert die Studienteilnahme ebenso wie der generelle Wunsch, Forschung zu unterstützen. Die Gewissheit, dass in jedem Fall mit einer Symptomlinderung zu rechnen ist, trägt wesentlich zur Beruhigung der Patientinnen bei. Auch das Vertrauen zum Hausarzt spielt eine wichtige Rolle im Entscheidungsprozess. Studienablehnerinnen äußerten deutliche Präferenzen hinsichtlich der Behandlung, was zusammen mit individuellen Gründen zur Ablehnung führte.Fazit: Um die Rekrutierungsbedingungen für zukünftige klinische Studien zu akuten Erkrankungen im hausärztlichen Setting zu optimieren, sollten die folgenden Schlüsselaspekte berücksichtig werden: Betonung des persönlichen Benefits für die Patienten, Auswahl patientenrelevanter Studienthemen, Gewährleistung maximaler Sicherheit, geringer Aufwand durch Studienprozeduren.
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To describe the inappropriate use of traditional non-steroidal anti-inflammatory drugs (tNSAIDs) in elderly subjects in the CADEUS cohort using the Beers 2003 criteria modified by recommendations from the French Medicines Agency.
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Branched-chain fatty acids are common components of the human diet (phytanic acid) or are produced endogenously (bile acids), and are also used as medicines (ibuprofen). Owing to their branched-chain structure, they are metabolized in peroxisomes. In the case of phytanic acid, the presence of a 3-methyl group prevents beta-oxidation, and instead it undergoes one round of alpha-oxidation to allow further metabolism. Defects in this process give rise to neurological diseases and cancer. Dr Brian F. Gibberd was one of the first U.K. physicians to recognize the importance of these peroxisomal metabolic pathways in clinical medicine, and pioneered their study. This obituary recognizes his many achievements in neurology and especially in the treatment of peroxisomal disorders. The following four papers from this mini-symposium entitled 'Advances in peroxisomal alpha-, beta- and omega-oxidation' describe work done in this area as part of a collaborative study in which Dr Gibberd played a key role. This work was presented as part of the Cardiovascular Bioscience focused topic at the Life Sciences 2007 conference, and this mini-symposium was dedicated to Dr Gibberd and his important contributions to this field.
Among 2693 total ADRs reported, 872 (33.04%) were CDRs. Antimicrobials (55.5%) were the main drugs involved followed by NSAIDs (18.56%) and steroids (12.61%). Maculopapular rash (37.73%) followed by fixed drug eruption (17.2%) and urticaria (14.56%) were the most frequently observed CDRs. The common drugs causing CDRs were cotrimoxazole (20.41%), topical steroids (betamethasone), ibuprofen (7.91%), ampicillin (6.54%), diclofenac (4.7%) and iron dextran (3.44%).
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This study aimed to compare the analgesic effects of intravenous ibuprofen and intravenous morphine titration for femoral shaft fractures in adult patients. In total, 293 participants were enrolled and randomly received intravenous ibuprofen or intravenous morphine titration. Their visual analogue scale (VAS) results were recorded every 5 minutes after the first administration. The VAS scores before and during transport were also measured. Meanwhile, the type and frequency of the adverse effects were also recorded in both groups. Patients treated with morphine showed a faster and greater reduction in the VAS than those in the ibuprofen group within 1 hour after the first administration. Interestingly, intravenous morphine titration provided consistent analgesia even during the further transport. No significant immediate adverse event was observed in all of the participants, except for sedation, which might be beneficial for keeping the patient quiet and might not be arbitrarily attributed to adverse effects. No addiction was noted in the morphine group. This study demonstrated that intravenous morphine titration is a faster and more efficient analgesia for femoral shaft fractures than ibuprofen in adult patients immediately after injury.