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Contains fulltext : 283780.pdf (Publisher’s version ) (Open Access)

Contains fulltext : 175572.pdf (publisher's version ) (Open Access), PURPOSE: Varus medial knee osteoarthritis (OA) can be treated with a closing-wedge (CW) or opening-wedge (OW) high tibial osteotomy (HTO). Little is known about the adverse event (AE) rate of these techniques. The purpose of this study was to examine the AE rate and survival rate of a consecutive series of 412 patients undergoing CW- or OW-HTO. METHODS: Medical records were retrospectively screened, and all patients who underwent HTO from 1993 to 2012 at the Erasmus University Medical Centre were assessed with a self-administered questionnaire. Patients filled in the intermittent and constant osteoarthritis pain score, knee injury and osteoarthritis outcome score, and a general questionnaire focusing on AE. RESULTS: Medical records of 412 patients (354 CW- and 112 OW-HTOs) were screened. Of the 358 eligible patients, 291 (81 %) returned their questionnaire. A total of 80 AE (17 %) were found in 466 osteotomies. In the CW-group, 47 (13 %) serious adverse events (SAE) and 2 (0.6 %) AE were found. In the OW-group, 17 (15 %) SAE and 14 (13 %) AE were found. The most common AE was in 14 (4 %) patients of the CW-group sensory palsy of the common peroneal nerve. The most common AE in the OW-group was persistent pain at the iliac crest [11 (9.8 %) patients]. Hardware was removed in 48 % of the CW-osteotomies and 71 % of the OW-osteotomies (p < 0.05). The probability of survival was 75 % after 10 years in the CW-group versus 90 % in the OW-group (p < 0.05). In both groups, an equal number of patients were "in need for prosthesis" according to OARSI criteria. CONCLUSION: OW-HTO was associated with more AE than CW-HTO. OW-HTO resulted in better survival than CW-HTO. However, in both groups an equal number of patients were in need for prosthesis. LEVEL OF EVIDENCE: Retrospective comparative study, Level III.

Radboud Universiteit Nijmegen, 4 juli 2011, Promotor : Booij, L.H.D.J. Co-promotores : Driessen, J.J., Egmond, J. van, Snoeck, M.M.J., Contains fulltext : 89942.pdf (publisher's version ) (Open Access)

Item does not contain fulltext, BACKGROUND AND OBJECTIVE: 3-Desacetyl-vecuronium is an active metabolite of the neuromuscular blocking agent (NMBA) vecuronium, which might lead to residual paralysis after prolonged administration of vecuronium in critically ill patients with renal failure. This study investigated the ability of sugammadex to reverse 3-desacetyl-vecuronium-induced neuromuscular block (NMB) in the anaesthetised rhesus monkey. METHODS: Experiments were performed in anaesthetised female rhesus monkeys. After bolus intravenous injection of vecuronium (n = 8) or 3-desacetyl-vecuronium (n = 8) 10 mug kg(-1) (ED90), a continuous infusion of the same NMBA was started to maintain the first twitch of the train-of-four (TOF) at 10% of baseline value. The infusion was stopped and NMB recovered spontaneously. The procedure was repeated, but immediately after stopping the infusion, an intravenous bolus dose of sugammadex 0.5 or 1.0 mg kg(-1) was given. For each NMBA, four placebo experiments were performed, in which the second recovery from NMB was also spontaneous. For all experiments, time to recovery of the TOF ratio to 90% was retrieved. RESULTS: After administration of sugammadex for reversal of 3-desacetyl-vecuronium-induced NMB, recovery was significantly faster than spontaneous recovery. Mean time to recovery of TOF to 90% was 3.2 min (sugammadex 0.5 mg kg(-1)) and 2.6 min (1.0 mg kg(-1)), compared to spontaneous recovery (17.6 min). For vecuronium-induced NMB, mean time to recovery of TOF to 90% was 17.1 min (0.5 mg kg(-1)) and 4.6 min (1.0 mg kg(-1)), compared to spontaneous recovery (23.4 min). CONCLUSION: Sugammadex rapidly and effectively reversed 3-desacetyl-vecuronium-induced NMB in the rhesus monkey, at a lower dose than that needed to reverse vecuronium-induced NMB.

Item does not contain fulltext, PURPOSE: Sugammadex is a selective relaxant binding agent designed to encapsulate the aminosteroidal neuromuscular blocking agent rocuronium, thereby reversing its effect. Both sugammadex and the sugammadex-rocuronium complex are eliminated by the kidneys. This study investigated the effect of sugammadex on recovery of rocuronium-induced neuromuscular block in cats with clamped renal pedicles, as a model for acute renal failure. METHODS: Twelve male cats were divided into two groups and anesthetized with medetomidine, ketamine, and alpha-chloralose. The cats were intubated and ventilated with a mixture of oxygen and air. Neuromuscular monitoring was performed by single twitch monitoring. Rocuronium 0.5 mg/kg i.v. was administered. After spontaneous recovery from neuromuscular block, both renal pedicles were ligated. A second dose of rocuronium 0.5 mg/kg i.v. was given. One minute after disappearance of the twitches, in Group 1 placebo (0.9% saline) and in Group 2 sugammadex 5.0 mg/kg i.v. was administered. Onset time, duration of neuromuscular block, and time to recovery to 25, 50, 75, and 90% were determined. Results : After renal pedicle ligation, sugammadex reversed rocuronium-induced neuromuscular block significantly faster than spontaneous recovery. Mean time (SEM) to 90% recovery of the twitch response was 4.7 (0.25) min (Group 2) versus 31.1 (5.0) min (Group 1) (p < 0.0001). No signs of recurrence of neuromuscular block were observed for 90 min after complete twitch restoration. Sugammadex caused no significant cardiovascular effects. CONCLUSION: Sugammadex rapidly and effectively reversed rocuronium-induced neuromuscular block in anesthetized cats, even when both renal pedicles were ligated and renal elimination of the drugs was no longer possible.

Contains fulltext : 89691.pdf (publisher's version ) (Closed access), A rat model of osteoarthritis was used to investigate the effect of pre-treatment with capsaicin on the symptoms of osteoarthritis induced by the injection of monosodium iodoacetate. This model mimics both histopathology and symptoms associated of human osteoarthritis. Injection of monosodium iodoacetate, an inhibitor of glycolysis, into the femorotibial joints of rodents promotes loss of articular trabecular bone and invokes pain symptoms similar to those noted in human osteoarthritis. Twenty rats were divided in two groups either receiving placebo or monosodium iodoacetate. Each group was subdivided in two groups either receiving pre-treatment with capsaicin two weeks before monosodium iodoacetate injection or not, resulting in four groups of five rats each. The impact of a single intra-articular administration of capsaicin (0.5%) on the generation of evoked mechanical pain (hind limb weight bearing, automated von Frey monofilament and RotaRod tests) and bone lesions (micro-CT scan radiographic analyses of bone structure) following monosodium iodoacetate-induced osteoarthritis in rats was determined. Evoked mechanical pain as monitored over a period of 4 weeks after monosodium iodoacetate injection was abolished in capsaicin pre-treated animals and pain values are comparable to those of capsaicin controls. Chronic joint pathological changes such as bone erosion and trabecular damage were significantly reduced by pre-treatment with a single administration of capsaicin. Decrease of bone volume was considerably ameliorated and trabecular connectivity was substantially better in capsaicin pre-treated animals. Capsaicin, an agonist activator of the vanilloid nociceptors (TRPV1), appears to be effective in protecting bone from arthritic damage. The present results support the hypothesis that capsaicin-sensitive sensory neurons contribute to bone lesions in the monosodium iodoacetate-induced osteoarthritis rat model.

1 juni 2010, Contains fulltext : 89110.pdf (publisher's version ) (Closed access)

1 maart 2010, Item does not contain fulltext, A neuromuscular blocking drug (NMBD) induced neuromuscular blockade (NMB) in patients with myasthenia gravis usually dissipates either spontaneously or by administration of neostigmine. We administered sugammadex to a patient with myasthenia gravis to reverse a rocuronium-induced profound NMB. NMBDs predispose such patients to severe postoperative residual paralysis and respiratory complications. Sugammadex binds steroidal NMBDs and, therefore reverses a rocuronium or vecuronium-induced NMB, without interfering with cholinergic transmission. A rapid and complete recovery from profound NMB was achieved and no adverse events were observed. This case suggests that sugammadex is a safe and effective antagonist of a rocuronium induced NMB blockade in patients with myasthenia gravis.

Internationale samenwerking speelt in de eenentwintigste eeuw een steeds belangrijkere rol. Landen gaan steeds vaker over tot harmonisering van beleid. Hoewel deze harmonisering voordelen brengt zijn er ook belangrijke nadelen aan verbonden. Landen maken hoge aanpassingskosten en geven een deel van hun soevereiniteit op. Uit dit probleem rijst de vraag: ‘waarom gaan landen over tot beleidsaanpassing door middel van harmonisatie?’ Het antwoord op deze vraag is gezocht door onderzoek te doen naar de invoering van het bachelor-mastersysteem in Nederland, naar aanleiding van deelname aan het Bolognaproces. Deze casus heeft als voordeel dat het een terrein behandelt, namelijk onderwijs, waarop traditioneel gezien geen internationale harmonisatie plaatsvindt. Tevens bevindt het Bolognaproces zich buiten de context van de Europese Unie, deelname aan het proces is daarom vrijwillig. Ook is het verloop van het proces uitgebreid gedocumenteerd. Uit onderzoek naar de wetenschappelijke literatuur over harmonisatie en beleidsaanpassing is gebleken dat economische motieven, enthousiasme over voorgaande harmonisatieprocessen en aanpassingsdruk belangrijke redenen voor landen zijn om over te gaan tot beleidsaanpassing door middel van deelname aan harmonisatieprocessen. Hoge kosten, negatieve ervaringen met harmonisatieprocessen en opgave van soevereiniteit fungeren als belangrijke argumenten tegen harmonisatie. Deze kenmerken zijn verenigd in een model dat de aanpassingsdruk voor beleidsaanpassing van het land in kwestie meet. Door onderzoek naar het heersende sectorale beleid, de nationale bestuurlijke tradities en onderzoek naar de hervormingscapaciteit van een land, en de verschillen tussen deze zaken en het nieuwe beleid, kan een hypothese opgesteld worden over de waarschijnlijkheid van beleidsaanpassing in het land in kwestie. Dit model brengt tevens de motieven voor landen om over te gaan tot beleidsaanpassing door middel van harmonisatie aan het licht. Na toepassing van het

01 juni 2010, Contains fulltext : 89883.pdf (publisher's version ) (Closed access), We measured acceleromyography and mechanomyography simultaneously with monitoring of rocuronium-induced neuromuscular block in four patients with myotonic dystrophy type 1. Furthermore, we compared neuromuscular block measures from these patients with those from normal controls from previous studies. In myotonic dystrophy type 1 patients, the dose-response curve obtained with acceleromyography was steeper and right-shifted compared with that obtained using mechanomyography. However, the effective doses to produce 95% neuromuscular block determined with both acceleromyography and mechanomyography were similar to each other and to values found in normal patients. In the three myotonic dystrophy type 1 patients with mild to moderate disease, times to recovery from block were similar to those observed in normal controls. In both patients and normal controls, neuromuscular block recovered faster with acceleromyography. However, in one patient with severe muscle wasting, recovery of neuromuscular block was prolonged. We conclude that mechanomyography and acceleromyography cannot be used interchangeably to monitor neuromuscular block in myotonic dystrophy type 1 patients.

Contains fulltext : 80245.pdf (publisher's version ) (Closed access), BACKGROUND: Intravenous opioid therapy is frequently used for postoperative pain management in children after orthopedic surgery but causes side effects such as respiratory depression, vomiting, sedation, and urinary retention. To investigate whether a continuous incisional fascia iliaca compartment (FIC) block provides more effective postoperative pain relief with fewer side effects than IV morphine, we performed a prospective, double-blind, randomized study to compare both techniques. METHODS: Thirty children (ASA physical status I-II) aged 3 mo to 6 yr undergoing a pelvic osteotomy were included in the study. The children were randomized for either morphine IV and placebo (saline) via a FIC catheter (Group M) or placebo (saline) IV and ropivacaine via a FIC catheter (Group R). All patients received general anesthesia using inhaled sevoflurane and IV fentanyl. Perioperatively, a FIC catheter was placed by the surgeon. All patients received either a bolus dose of morphine IV (Group M) or ropivacaine 0.75% via the FIC catheter (Group R) at the end of surgery. Postoperatively, Group M received morphine IV 20 microg x kg(-1) x h(-1) and Group R ropivacaine 0.2% 0.1 mL x kg(-1) x h(-1) via the FIC catheter. In both groups, saline was administered along the other route. All children were assessed for pain, sedation, time until first oral intake, and adverse effects for 48 h postoperatively. During this period, all children had a urinary catheter. RESULTS: The study was completed by 28 children. In the anesthetic recovery room, children in Group M had significantly higher pain scores. These children were also significantly more sedated during the study period. The incidence of vomiting did not differ between the groups; however, children in Group R had first oral intake significantly earlier than Group M. A local retrospective study revealed an incidence of urinary retention of 4.7% in the ropivacaine-treated patients and 39% in the morphine-treated patients. CONCLUSIONS

Contains fulltext : 80952.pdf (publisher's version ) (Closed access), BACKGROUND: A continuous femoral nerve block is frequently used as an adjunct therapy after total knee arthroplasty (TKA). However, there is still debate on its benefits. METHODS: In this prospective, randomized study, patients received a basic analgesic regimen of paracetamol and dicloflenac for the first 48 h postoperatively. In addition, the study group received a continuous femoral nerve block. A morphine patient-controlled analgesia pump was also available as a rescue analgesic to all the patients. Patients' numeric rating scores for pain, the amount of morphine consumed and its side effects during the first 48 h were recorded. Knee flexion angles achieved during the first week were registered. Three months postoperatively, patients completed Western Ontario and McMaster Universities Osteoarthritis Index and Knee Society Score. Results : The study group (n=27) had less pain (P=0.0016) during the first 48 h, was more satisfied with the analgesia (P<0.001) and used less morphine (P=0.007) compared with the control group (n=26). Fewer patients were nauseated, vomited or were drowsy in the study group (P=0.001). Also, the study group achieved better knee flexion in the first 6 days after surgery (P=0.001), with more patients reaching 90 degrees flexion than the control group. However, after 3 months, there were no significant functional differences between the groups. CONCLUSION: A continuous femoral nerve block leads to better analgesia, less morphine consumption and less morphine-related side effects after TKA. Early functional recovery is improved, resulting in more patients reaching 90 degrees knee flexion after 6 days. However, after 3 months, no significant functional benefits were found.

Contains fulltext : 81304.pdf (publisher's version ) (Closed access), BACKGROUND: Fos expression in the lumbar spinal cord, resulting from a noxious electrical stimulus at the hindpaw, is hypothesized to originate from three sources: direct sensory input of the noxious stimulus, local interactions in the spinal cord, and input of modulating signals from supraspinal regions. Our aim in this study was to discriminate among these sources by eliminating the supraspinal input. METHODS: Therefore, a spinal block was administered in male Wistar rats by administering a local anesthetic (bupivacaine) through an intrathecal catheter at the mid-thoracic level. This thoracic spinal block completely suppressed the noxious stimulation-induced withdrawal reflex that is normally elicited by electrical stimulus. Fos immunoreactivity (Fos-IR) was quantified in all laminae of the L4 segment of the spinal cord. RESULTS: Noxious stimulation resulted in a general and strong increase in Fos-IR in the ipsilateral dorsal horn, mainly in Laminae I, II, and V. Thoracic spinal block caused a remarkable increase in the amount of Fos-IR in Lamina V, but had no significant effect on the Fos-IR in Laminae I and II. CONCLUSIONS: The increase in Fos-IR in Lamina V may have resulted from the interruption of a pain-modulating descending mechanism from the brain. A known modulating descending mechanism is the serotonergic system, controlled by the periaqueductal gray. This system inhibits the neurons in the superficial laminae. Another nonserotonergic system originates in the anterior pretectal nucleus. The latter facilitates neurons in the superficial laminae, while neurons in Lamina V are inhibited. We conclude that both systems are probably involved in the observed effects of the peripheral noxious stimulation given in the present model.

Contains fulltext : 80056.pdf (publisher's version ) (Closed access), Isoflurane (ISO) can be a valuable alternative for alpha-chloralose (ACL) anesthesia in functional MRI (fMRI) studies. Therefore, we compared the efficacy of the blood oxygen level dependent (BOLD) effect in fMRI studies during ISO and ACL anesthesia sequentially in the same animals. After non-invasive instrumentation for ventilation and monitoring, series of T2* weighted MR images were acquired during forepaw stimulation, first under ISO, then followed by ACL anesthesia. The results demonstrated that ISO and ACL were both suitable to perform this fMRI experiment. The center of activation was at the same stereotactic position for both anesthetics and matched the primary somatosensory cortex (S1). Under the applied conditions, the BOLD response during ISO anesthesia declined in magnitude during the first stimulation period, as compared to ACL. From this study, we conclude that since ISO has several positive properties in comparison to ACL, including fast pharmacokinetics and suitability for repeated measurements, it is a valuable alternative for anesthesia in fMRI studies of rats.

Contains fulltext : 81733.pdf (publisher's version ) (Closed access), OBJECTIVE: To determine if treatment of longstanding complex regional pain syndrome type 1, focusing on functional improvement only while neglecting pain, results in clinical improvement of this syndrome. DESIGN: Prospective description of a case series of 106 patients. SETTING: Outpatient clinic for rehabilitation. INTERVENTIONS: Physical therapy of the affected limb directed at a functional improvement only while neglecting the pain, was performed following an extensive explanation. Normal use of the limb between the treatments was encouraged despite pain. A maximum of five of these sessions were performed in three months. MEASURES: Radboud Skills Test was used to monitor functional improvement of the arms. Speed and walking distance was used as the measure of outcome for the legs. Results : The function of the affected arm or leg improved in 95 patients. Full functional recovery was experienced in 49 (46%) of them. A reduction in pain presented in 75 patients. In 23 patients functional recovery was reached despite an increase in pain. Four patients stopped early due to pain increase. CONCLUSIONS: Our results suggest that 'pain exposure physical therapy' is effective and safe for patients who are unresponsive to accepted standard therapies. Avoiding the use of a limb due to pain will result in loss of function. Forced usage of limbs restores the function, reverses these adaptive processes and leads to regain of control by practice with a reduction of pain in most cases.

Contains fulltext : 79523.pdf (publisher's version ) (Closed access), BACKGROUND: Mechanical ventilation (MV) can induce lung injury. Proinflammatory cytokines have been shown to play an important role in the development of ventilator-induced lung injury. Previously, the authors have shown a role for Toll-like receptor 4 signaling. The current study aims to investigate the role of Toll/interleukin-1 receptor domain-containing adapter-inducing interferon-beta (TRIF), a protein downstream of Toll-like receptors, in the development of the inflammatory response after MV in healthy mice. METHODS: Wild-type C57BL6 and TRIF mutant mice were mechanically ventilated for 4 h. Lung tissue and plasma was used to investigate changes in cytokine profile, leukocyte influx, and nuclear factor-kappaB activity. In addition, experiments were performed to assess the role of TRIF in changes in cardiopulmonary physiology after MV. RESULTS: MV significantly increased messenger RNA expression of interleukin (IL)-1beta in wild-type mice, but not in TRIF mutant mice. In lung homogenates, MV increased levels of IL-1alpha, IL-1beta, and keratinocyte-derived chemokine in wild-type mice. In contrast, in TRIF mutant mice, only a minor increase in IL-1beta and keratinocyte-derived chemokine was found after MV. Nuclear factor-kappaB activity after MV was significantly lower in TRIF mutant mice compared with wild-type mice. In plasma, MV increased levels of IL-6 and keratinocyte-derived chemokine. In TRIF mutant mice, no increase of IL-6 was found after MV, and the increase in keratinocyte-derived chemokine appeared less pronounced. TRIF deletion did not affect cardiopulmonary physiology after MV. CONCLUSIONS: The current study supports a prominent role for TRIF in the development of the pulmonary and systemic inflammatory response after MV.

Contains fulltext : 80280.pdf (publisher's version ) (Closed access), A review is presented of animal studies of the selective steroidal neuromuscular blocking drug binding agent sugammadex. These studies demonstrate that sugammadex is faster in onset than the currently used acetylcholinesterase inhibitors, has no muscarinic effects, and is characterised by lack of adverse effects on other organs. These results offer support for the further development of sugammadex for clinical use in humans.

RU Radboud Universiteit Nijmegen, 27 augustus 2009, Promotores : Ritskes-Hoitinga, M., Vissers, K.C.P. Co-promotor : Egmond, J. van, Contains fulltext : 81162.pdf (Publisher’s version ) (Open Access)

Contains fulltext : 80045.pdf (publisher's version ) (Closed access), BACKGROUND: Mechanical ventilation (MV) induces an inflammatory response in healthy lungs. The resulting pro-inflammatory state is a risk factor for ventilator-induced lung injury and peripheral organ dysfunction. Isoflurane is known to have protective immunological effects on different organ systems. We tested the hypothesis that the MV-induced inflammatory response in healthy lungs is reduced by isoflurane. METHODS: Healthy C57BL6 mice (n=34) were mechanically ventilated (tidal volume, 8 ml/kg; positive end-expiratory pressure, 4 cmH(2)O; and fraction of inspired oxygen, 0.4) for 4 h under general anesthesia using a mix of ketamine, medetomidine and atropine (KMA). Animals were divided into four groups: (1) Unventilated control group; (2) MV group using KMA anesthesia; (3) MV group using KMA with 0.25 MAC isoflurane; (4) MV group using KMA with 0.75 MAC isoflurane. Cytokine levels were measured in lung homogenate and plasma. Leukocytes were counted in lung tissue. RESULTS: Lung homogenates: MV increased pro-inflammatory cytokines. In mice receiving KMA+ isoflurane 0.75 MAC, no significant increase in interleukin (IL)-1beta was found compared with non-ventilated control mice. PLASMA: MV induced a systemic pro-inflammatory response. In mice anesthetized with KMA+ isoflurane (both 0.25 and 0.75 MAC), no significant increase in tumor necrosis factor (TNF)-alpha was found compared with non-ventilated control mice. CONCLUSIONS: The present study is the first to show that isoflurane attenuates the pulmonary IL-1beta and systemic TNF-alpha response following MV in healthy mice.

Contains fulltext : 81674.pdf (publisher's version ) (Closed access), A case is reported in which a child with Duchenne muscular dystrophy received a dose of sugammadex to reverse a rocuronium-induced profound neuromuscular block. Sugammadex is the first selective relaxant binding agent and reverses rocuronium- and vecuronium-induced neuromuscular block. A fast and efficient recovery from profound neuromuscular block was achieved, and no adverse events or other safety concerns were observed.