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OBJECTIVE: Oxygen has been used liberally in ICUs for a long time to prevent hypoxia in ICU- patients. Current evidence suggests that paO2 >300 mmHg should be avoided, it remains uncertain whether an "optimal level" exists. We investigated how "mild" hyperoxia influences diseases and in-hospital mortality. DESIGN: This is a retrospective study. SETTING: 112 mechanically ventilated ICU-patients were enrolled. PATIENTS OR PARTICIPANTS: 112 ventilated patients were included and categorized into two groups based on the median paO2 values measured in initial 24 h of mechanical ventilation: normoxia group (paO2 ≤ 100 mmHg, n = 43) and hyperoxia group patients (paO2 > 100 mmHg, n = 69). INTERVENTIONS: No interventions were performed. MAIN VARIABLES OF INTEREST: The primary outcome was the incidence of pulmonary events, the secondary outcomes included the incidence of other new organ dysfunctions and in-hospital mortality. RESULTS: The baseline characteristics, such as age, body mass index, lactate levels, and severity of disease scores, were similar in both groups. There were no statistically significant differences in the incidence of pulmonary events, infections, and new organ dysfunctions between the groups. 27 out of 69 patients (39.1%) in the "mild" hyperoxia group and 12 out of 43 patients (27.9%) in the normoxia group died during their ICU or hospital stay (p = 0.54). The mean APACHE Score was 29.4 (SD 7.9) in the normoxia group and 30.0 (SD 6.7) in the hyperoxia group (p = 0.62). CONCLUSIONS: We found no differences in pulmonary events, other coded diseases, and in-hospital mortality between both groups. It remains still unclear what the "best oxygen regime" is for intensive care patients.
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INTRODUCTION: This case report documents a postoperative, incomplete sensorimotor paraparesis from thoracic vertebral body 6 (Th6) after combined anesthesia for upper abdominal surgery in a patient who had a thoracic localization of spinal epidural lipomatosis (SEL). CASE PRESENTATION: The patient was treated in our clinic with a thoracic epidural catheter (TEA) for perioperative analgesia during a partial duodenopancreatectomy. Paraparetic symptoms occurred 20 hours after surgery. Initial MRI did not show bleeding, infection or spinal cord damage and the neurosurgeon consultants recommended observation. The neurological examination and the third follow-up MRI on 15th postoperative day showed ventrolateral damage of the spinal cord at level Th6. It is possible that local anesthetic compressed the spinal cord in addition to the existing lipomatosis and the thoracic kyphosis. The paraparesis improved during follow-up paraplegiologic treatment. CONCLUSION: So far, only two uncomplicated lumbar epidural catheter anesthesias have been described in patients who had a lumbar SEL. Epidural catheter anesthesia is a safe and effective method of pain control. But it is important to carefully identify and stratify patients with risk factors during the premedication visit. In patients who had kyphosis and thoracic localization of SEL, TEA may only be used after a risk-benefit assessment.
Subject(s)
Anesthesia, Epidural , Lipomatosis , Thoracic Vertebrae , Humans , Anesthesia, Epidural/adverse effects , Lipomatosis/diagnostic imaging , Thoracic Vertebrae/diagnostic imaging , Thoracic Vertebrae/surgery , Pancreaticoduodenectomy/adverse effects , Male , Paraparesis/etiology , Middle Aged , Magnetic Resonance Imaging , AgedABSTRACT
Triggering receptor expressed on myeloid cells-1 (TREM-1) is a pattern recognition receptor and plays a critical role in the immune response. TREM-1 activation leads to the production and release of proinflammatory cytokines, chemokines, as well as its own expression and circulating levels of the cleaved soluble extracellular portion of TREM-1 (sTREM-1). Because patients with sepsis and septic shock show elevated sTREM-1 levels, TREM-1 has attracted attention as an important contributor to the inadequate immune response in this often-deadly condition. Since 2001, when the first blockade of TREM-1 in sepsis was performed, many potential TREM-1 inhibitors have been established in animal models. However, only one of them, nangibotide, has entered clinical trials, which have yielded promising data for future treatment of sepsis, septic shock, and other inflammatory disease such as COVID-19. This review discusses the TREM-1 pathway and important ligands, and highlights the development of novel inhibitors as well as their clinical potential for targeted treatment of various inflammatory conditions.
Subject(s)
Sepsis , Shock, Septic , Triggering Receptor Expressed on Myeloid Cells-1 , Animals , Humans , Cytokines , Sepsis/drug therapy , Triggering Receptor Expressed on Myeloid Cells-1/metabolismABSTRACT
(1) Background: Postdural puncture headache (PDPH) remains a serious complication in obstetric patients. While the epidural blood patch represents the current gold standard in therapy, a growing number of alternative measures are thought to be beneficial for clinical management. The purpose of this study was to retrospectively analyze the efficacy of intranasal lidocaine administration to treat PDPH in obstetrics at our university hospital; (2) Methods: A retrospective analysis of the medical records of patients with PDPH has been performed focusing on the techniques of administration, dosing, treatment duration, impact on pain intensity as well as side effects of intranasal lidocaine; (3) Results: During the study period, 5610 obstetric patients received neuraxial anesthesia, of whom 43 (0.77%) developed PDPH. About one third of the patients with PDPH after spinal anesthesia (n = 8), epidural anesthesia (n = 5) or both (n = 2) were treated with intranasal lidocaine. Lidocaine was administered either via gauze compresses (GC, n = 4), a mucosal atomization device (MAD, n = 8) or with a second-line mucosal atomization device due to low gauze compress efficacy (n = 3). All patients treated with lidocaine refused the epidural blood patch. Nebulization of lidocaine resulted in a significant reduction in pain intensity after the first dose (p = 0.008). No relevant side effects developed except sporadic temporal pharyngeal numbness. The utilization of the mucosal atomization device averted the necessity for an epidural blood patch, whether employed as the primary or secondary approach; (4) Conclusions: Our data imply that the mucosal atomization device enhances the efficacy of intranasal lidocaine administration in obstetric patients suffering from PDPH.
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BACKGROUND: Postoperative immunosuppression has been recognized as an important driver of surgery-related morbidity and mortality. It is characterized by lymphocyte depression and impaired monocyte capability to present foreign antigens to T-cells via Major Histocompatibility Complex, Class II (MHC-II) molecules. In patients with postoperative abdominal sepsis, we previously detected a persisting differential binding of the CCCTC-Binding Factor (CTCF), a superordinate regulator of transcription, inside the MHC-II region with specific impact on human leucocyte antigen (HLA) gene expression. In this prospective exploratory study, we investigated to which extent major surgery affects the MHC-II region of circulating CD14+-monocytes. RESULTS: In non-immunocompromised patients undergoing elective major abdominal surgery, a postoperative loss of monocyte HLA-DR surface receptor density was accompanied by a decline in the transcription levels of the classical MHC-II genes HLA-DRA, HLA-DRB1, HLA-DPA1 and HLA-DPB1. The surgical event decreased the expression of the transcriptional MHC-II regulators CIITA and CTCF and led to a lower CTCF enrichment at an intergenic sequence within the HLA-DR subregion. During the observation period, we found a slow and only incomplete restoration of monocyte HLA-DR surface receptor density as well as a partial recovery of CIITA, HLA-DRA and HLA-DRB1 expression. In contrast, transcription of HLA-DPA1, HLA-DPB1, CTCF and binding of CTCF within the MHC-II remained altered. CONCLUSION: In circulating monocytes, major surgery does not globally affect MHC-II transcription but rather induces specific changes in the expression of selected HLA genes, followed by differential recovery patterns and accompanied by a prolonged reduction of CTCF expression and binding within the MHC-II region. Our results hint toward a long-lasting impact of a major surgical intervention on monocyte functionality, possibly mediated by epigenetic changes that endure the life span of the individual cell.
Subject(s)
Gene Expression Regulation , Monocytes , Humans , CCCTC-Binding Factor/genetics , HLA-DR alpha-Chains/genetics , HLA-DRB1 Chains/genetics , Prospective Studies , Genes, MHC Class II , Histocompatibility Antigens Class II/geneticsABSTRACT
Introduction: Kidney dysfunction is common in patients with aortic stenosis (AS) and correction of the aortic valve by transcatheter aortic valve implantation (TAVI) often affects kidney function. This may be due to microcirculatory changes. Methods: We evaluated skin microcirculation with a hyperspectral imaging (HSI) system, and compared tissue oxygenation (StO2), near-infrared perfusion index (NIR), tissue hemoglobin index (THI) and tissue water index (TWI) in 40 patients undergoing TAVI versus 20 control patients. HSI parameters were measured before TAVI (t1), directly after TAVI (t2), and on postinterventional day 3 (t3). The primary outcome was the correlation of tissue oxygenation (StO2) to the creatinine level after TAVI. Results: We performed 116 HSI image recordings in patients undergoing TAVI for the treatment of severe aortic stenosis and 20 HSI image recordings in control patients. Patients with AS had a lower THI at the palm (p = 0.034) and a higher TWI at the fingertips (p = 0.003) in comparison to control patients. TAVI led to an increase of TWI, but had no uniform enduring effect on StO2 and THI. Tissue oxygenation StO2 at both measurement sites correlated negatively with creatinine levels after TAVI at t2 (palm: ρ = -0.415; p = 0.009; fingertip: ρ = -0.519; p < 0.001) and t3 (palm: ρ = -0.427; p = 0.008; fingertip: ρ = -0.398; p = 0.013). Patients with higher THI at t3 reported higher physical capacity and general health scores 120 days after TAVI. Conclusion: HSI is a promising technique for periinterventional monitoring of tissue oxygenation and microcirculatory perfusion quality, which are related to kidney function, physical capacity, and clinical outcomes after TAVI. Clinical trial registration: https://drks.de/search/de/trial, identifier DRKS00024765.
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Notch signaling, a highly conserved pathway in mammals, is crucial for differentiation and homeostasis of immune cells. Besides, this pathway is also directly involved in the transmission of immune signals. Notch signaling per se does not have a clear pro- or anti-inflammatory effect, but rather its impact is highly dependent on the immune cell type and the cellular environment, modulating several inflammatory conditions including sepsis, and therefore significantly impacts the course of disease. In this review, we will discuss the contribution of Notch signaling on the clinical picture of systemic inflammatory diseases, especially sepsis. Specifically, we will review its role during immune cell development and its contribution to the modulation of organ-specific immune responses. Finally, we will evaluate to what extent manipulation of the Notch signaling pathway could be a future therapeutic strategy.
Subject(s)
Receptors, Notch , Sepsis , Animals , Humans , Receptors, Notch/metabolism , Signal Transduction , Cell Differentiation , Inflammation , Mammals/metabolismABSTRACT
Xlinked hypophosphatemia (XLH) is a phosphate wasting disorder. Typical serum constellations include low serum phosphate as well as high alkaline phosphatase (ALP) and fibroblast growth factor 23 (FGF-23 ) levels. Adult XLH patients usually suffer from (pseudo)fractures, enthesopathies, impaired mobility, and osteoarthritis. We report the case of a middle-aged woman with clinically mild disease, relatively balanced laboratory values, but bone non-healing of the femur post-surgery. Transiliac bone biopsy revealed pronounced osteomalacia and severe deterioration of bone microstructure. Due to the lack of XLH-typical symptoms, the patient was not substituted with calcitriol and phosphate in adulthood. Thus, laboratory findings and radiological examinations do not necessarily reflect bone metabolism in XLH. Bone biopsies should be considered in unclear cases or prior to surgery in adults with XLH.
Subject(s)
Familial Hypophosphatemic Rickets , Osteomalacia , Middle Aged , Female , Humans , Adult , Familial Hypophosphatemic Rickets/diagnosis , Phosphates/metabolism , Bone and Bones , Osteomalacia/diagnosis , Biopsy , Fibroblast Growth FactorsABSTRACT
BACKGROUND: High-energy injuries of the anterior pelvic ring and especially disruptions of the pubic symphysis usually require surgical stabilization. There is a conflict between biomechanical stability and size in the surgical approach. We have previously presented a minimally invasive approach for symphyseal plating. METHODS: Our current endoscopic surgical technique is presented step-by-step and is illustrated in a video. The results and courses of the first seven patients treated with the EASY preparation are presented. RESULTS: In all seven patients, the EASY preparation was successful. In four of the seven patients with an anterior pelvic ring injury, we performed a complete endoscopic plate osteosynthesis of the pubic symphysis. One patient gave consent only for endoscopic preparation, in one patient, we converted to open plate due to ventilation problems, and in one patient, the superior pubic rami fracture was stable. There were no surgical complications. CONCLUSION: The EASY is a feasible minimally invasive preparation technique to stabilize anterior pelvic ring injuries in the most biomechanically stable manner by performing plate osteosynthesis. However, further scientific monitoring is necessary to improve the technique and validate our data.
Subject(s)
Fractures, Bone , Pelvic Bones , Pubic Symphysis , Humans , Fractures, Bone/diagnostic imaging , Fractures, Bone/surgery , Fracture Fixation, Internal/methods , Pelvis , Pubic Symphysis/diagnostic imaging , Pubic Symphysis/surgery , Pubic Symphysis/injuries , Endoscopy/methods , Bone Plates , Pelvic Bones/diagnostic imaging , Pelvic Bones/surgery , Pelvic Bones/injuriesABSTRACT
INTRODUCTION: The "floating hip" is a rare and complex fracture involving the pelvis and the ipsilateral femur and is therefore difficult to treat. Data and studies on this topic are still scarce. The optimal strategy for surgical treatment and thus the resulting quality of treatment are still being debated; a femur-first strategy is often the preferred treatment. METHODS: Retrospectively, patients with a pelvic fracture treated at the Level I Trauma Centre of the University of Tübingen between 2003 and 2017 were identified. Patients with an additional ipsilateral femur fracture were identified in this collective. We compared the quality of treatment of pelvic fractures between floating and non-floating hip injuries. RESULTS: Proximal femur fractures were more common with pelvic ring fractures (n = 16) than with acetabular fractures (n = 1). Floating hip injuries occur more frequently in younger polytraumatised male patients. Pelvic fractures in floating hip injuries are operated more frequently (62.8% vs. 39.1%; p = 0.003) and the clinical course is significantly longer (27.8 ± 19.3 vs. 19.9 ± 23.1 days; p < 0.001). However, the quality of treatment of pelvic fracture, exemplified by morbidity (18.6% vs. 14.6%; p = 0.610) and mortality (7.0% vs. 2.6%; p = 0.108), shows no differences. CONCLUSION: Injury severity and complexity of pelvic fracture is significantly higher in floating hip injuries, but without affecting the resulting quality of treatment. A "femur first" treatment strategy is preferable. Algorithms for emergency treatment and definitive care are proposed in a flowchart.
Subject(s)
Femoral Fractures , Fractures, Bone , Hip Fractures , Hip Injuries , Pelvic Bones , Humans , Male , Retrospective Studies , Fractures, Bone/surgery , Femoral Fractures/surgery , Hip Fractures/epidemiology , Hip Fractures/surgery , Pelvic Bones/surgery , Pelvic Bones/injuries , Acetabulum/surgery , Acetabulum/injuriesABSTRACT
BACKGROUND: In preterm infants, spinal anesthesia (SpA) is recognized as an alternative to general anesthesia for inguinal hernia repair (IHR); however, some patients require supplemental anesthesia during surgery. The purpose of this study was to investigate the frequency and impact of supplemental anesthesia on perioperative care and adverse respiratory and hemodynamic events. METHODS: A retrospective study of preterm infants undergoing IHR at Heidelberg University Hospital within the first year of life between 2009 and 2018 was carried out. RESULTS: In total, 230 patients (255 surgeries) were investigated. Among 189 procedures completed using SpA 24 patients received supplemental anesthesia. Reasons for supplemental anesthesia included loss of anesthetic effect, returning motor response, and respiratory complications. Compared to SpA alone, no differences were found concerning hemodynamic parameters; however, patients requiring supplemental anesthesia displayed higher rates of postoperative oxygen supplementation and unexpected admission to the intensive care unit. The rate of perioperative apnea was 2.7%. Apneic events exclusively occurred after supplemental anesthesia. Bilateral IHR and duration of surgery were associated with the need for supplemental anesthesia. CONCLUSION: Whereas SpA might be favorable when compared to general anesthesia for IHR, the data indicate that particular caution is required in patients receiving supplemental anesthesia due to the possible risk for adverse respiratory events.
Subject(s)
Anesthesia, Spinal , Hernia, Inguinal , Infant , Humans , Infant, Newborn , Infant, Premature , Anesthesia, Spinal/adverse effects , Retrospective Studies , Hernia, Inguinal/surgery , Anesthesia, General/adverse effects , Apnea/etiologyABSTRACT
BACKGROUND: Fracture detection by artificial intelligence and especially Deep Convolutional Neural Networks (DCNN) is a topic of growing interest in current orthopaedic and radiological research. As learning a DCNN usually needs a large amount of training data, mostly frequent fractures as well as conventional X-ray are used. Therefore, less common fractures like acetabular fractures (AF) are underrepresented in the literature. The aim of this pilot study was to establish a DCNN for detection of AF using computer tomography (CT) scans. METHODS: Patients with an acetabular fracture were identified from the monocentric consecutive pelvic injury registry at the BG Trauma Center XXX from 01/2003â-â12/2019. All patients with unilateral AF and CT scans available in DICOM-format were included for further processing. All datasets were automatically anonymised and digitally post-processed. Extraction of the relevant region of interests was performed and the technique of data augmentation (DA) was implemented to artificially increase the number of training samples. A DCNN based on Med3D was used for autonomous fracture detection, using global average pooling (GAP) to reduce overfitting. RESULTS: From a total of 2,340 patients with a pelvic fracture, 654 patients suffered from an AF. After screening and post-processing of the datasets, a total of 159 datasets were enrolled for training of the algorithm. A random assignment into training datasets (80%) and test datasets (20%) was performed. The technique of bone area extraction, DA and GAP increased the accuracy of fracture detection from 58.8% (native DCNN) up to an accuracy of 82.8% despite the low number of datasets. CONCLUSION: The accuracy of fracture detection of our trained DCNN is comparable to published values despite the low number of training datasets. The techniques of bone extraction, DA and GAP are useful for increasing the detection rates of rare fractures by a DCNN. Based on the used DCNN in combination with the described techniques from this pilot study, the possibility of an automatic fracture classification of AF is under investigation in a multicentre study.
Subject(s)
Deep Learning , Hip Fractures , Spinal Fractures , Humans , Artificial Intelligence , Pilot Projects , Neural Networks, Computer , AlgorithmsABSTRACT
Open reduction and internal fixation are the gold standard for the treatment of dislocated acetabular fractures. A primary joint replacement is only justified in isolated cases. The indications are merely non-reconstructable acetabular fractures, accompanying displaced fractures of the femoral neck and non-reconstructable fractures of the femoral head.Because of the difficulties in achieving sufficient cup stability, joint replacement for the treatment of acetabular fractures regularly requires implants designed for revision arthroplasty. The Kocher-Langenbeck approach provides the most versatile options, as it enables simultaneous stabilization of the dorsal acetabular structures, which are essential for the stability of the cup.For primary joint replacement as a treatment of acetabular fractures, survival of the prosthetic cup is markedly worse when compared to elective primary joint replacement. Particularly in younger patients but also in aged patients, every effort should be made to achieve a press fit of the cup. In most cases, this will include reduction and fixation of the fracture for stabilization of the acetabulum prior to joint replacement. A staged approach with an early secondary replacement intervention seems to provide better overall results than simultaneous fracture fixation and joint replacement.
Subject(s)
Arthroplasty, Replacement, Hip , Hip Fractures , Spinal Fractures , Humans , Aged , Arthroplasty, Replacement, Hip/methods , Hip Fractures/surgery , Acetabulum/diagnostic imaging , Fracture Fixation, Internal/methods , Spinal Fractures/surgeryABSTRACT
In sepsis, both beneficial and detrimental effects of fresh frozen plasma (FFP) transfusion have been reported. The aim of this study was to analyze the indication for and effect of FFP transfusion in patients with septic shock. We performed a secondary analysis of a retrospective single-center cohort of all patients treated for septic shock at the interdisciplinary surgical intensive care unit (ICU) of the Heidelberg University Hospital. Septic shock was defined according to sepsis-3 criteria. To assess the effects of FFP administration in the early phase of septic shock, we compared patients with and without FFP transfusion during the first 48 h of septic shock. Patients who died during the first 48 h of septic shock were excluded from the analysis. Primary endpoints were 30- and 90-day mortality. A total of 261 patients were identified, of which 100 (38.3%) received FFP transfusion within the first 48 h after septic shock onset. The unmatched analysis showed a trend toward higher 30- and 90-d mortality in the FFP group (30 d: +7% p = 0.261; 90 d: +11.9% p = 0.061). In the propensity-matched analysis, 30- and 90-day mortality were similar between groups. Plasma administration did not influence fluid or vasopressor need, lactate levels, ICU stay, or days on a ventilator. We found no significant harm or associated benefit of FFP use in the early phase of septic shock. Finally, plasma should only be used in patients with a strong indication according to current recommendations, as a conclusive evaluation of the risk-benefit ratio for plasma transfusion in septic shock cannot be made based on the current data.
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Situations of both, intentional and inadvertent or accidental doping, necessitate consideration in today's doping controls, especially in the light of the substantial consequences that athletes are facing in case of so-called adverse analytical findings. The aim of this study was to investigate, whether a transdermal uptake of doping substances would be possible. In addition to the period of detectability of the particular substances or respective characteristic metabolites, the possibility of deducing the route of administration by metabolite patterns was also assessed. Twelve male subjects were included in the study. Four common anabolic androgenic steroids (AAS) were dissolved in dimethylsulfoxide to facilitate transdermal administration on different skin regions. One half of the test persons received only oxandrolone (17α-methyl-2-oxa-4,5α-dihydrotestosterone), and the other half were applied a mixture of oxandrolone, metandienone (17ß-hydroxy-17α-methylandrosta-1,4-dien-3-one), clostebol (4-chlorotestosterone-17ß-acetate) and dehydrochloromethyltestosterone (DHCMT). Urine samples were collected 1 h, 6 h and one sample per day for the next 14 consecutive days. Measurements were conducted on a tandem-gas chromatography-mass spectrometry (GC-MS/MS) or tandem-liquid chromatography-MS/MS (LC-MS/MS) system. Substance findings were obtained at least 1 day after application on nearly all skin locations. The results indicated inter-individual variability in detection windows, also varying between the different analytes and possible impact of skin location and skin thickness, respectively. Nevertheless, a rapid and rather long detectability of all substances (or respective metabolites) was given, in some cases within hours after administration and for up to 10-14 days. Hence, the transdermal application or exposure to the investigated AAS is a plausible scenario that warrants consideration in anti-doping.
Subject(s)
Anabolic Agents , Doping in Sports , Methandrostenolone , Acetates , Administration, Cutaneous , Anabolic Agents/urine , Chromatography, Liquid/methods , Dihydrotestosterone , Dimethyl Sulfoxide , Humans , Male , Methandrostenolone/urine , Oxandrolone/metabolism , Substance Abuse Detection/methods , Tandem Mass Spectrometry/methods , Testosterone/analogs & derivativesABSTRACT
Postdural puncture headache (PDPH) is one of the most important complications of peripartum neuraxial analgesia. Loss of cerebrospinal fluid volume and pressure as well as compensatory intracranial vasodilation are assumed to be responsible. Potentially severe long-term sequelae necessitate the correct diagnosis of PDPH, exclusion of relevant differential diagnoses (with atypical symptoms and when indicated via imaging techniques) and rapid initiation of effective treatment. Nonopioid analgesics, caffeine and occasionally theophylline, gabapentin and hydrocortisone are the cornerstones of pharmacological treatment, while the timely placement of an autologous epidural blood patch (EBP) represents the gold standard procedure when symptoms persist despite the use of analgesics. Procedures using neural treatment are promising alternatives, especially when an EBP is not desired by the patient or is contraindicated. Interdisciplinary and interprofessional consensus standard procedures can contribute to optimization of the clinical management of this relevant complication.
Subject(s)
Obstetrics , Post-Dural Puncture Headache , Blood Patch, Epidural/methods , Female , Humans , Pain , Post-Dural Puncture Headache/diagnosis , Pregnancy , Spinal Puncture/adverse effectsABSTRACT
Negative allosteric modulators of N-methyl- d-aspartate receptors containing the GluN2B subunit represent promising drug candidates for the treatment of various neurological disorders including stroke, epilepsy, and Parkinson's disease. To increase the bioavailability and GluN2B affinity, the phenol of the potent benzazepine-based inhibitor, WMS-1410 (3), was replaced bioisosterically by a benzoxazolone moiety and the phenylbutyl side chain was conformationally restricted in a phenylcyclohexyl substituent. A four-step, one-pot procedure transformed the oxazolo-benzazepine 7 into the phenylcyclohexyl derivative 11. The same protocol was applied to the methylated analog 12, which unexpectedly led to ring-contracted oxazolo-isoquinolines 18. This rearrangement was explained by the additional methyl moiety in the 8-position inhibiting the formation of the planar intermediate iminium ion with phenylcyclohexanone. The allyl protective group of 11 and 18 was removed with RhCl3 and HCl to obtain the tricyclic compounds 5 and 19 without substituent at the oxazolone ring. The structures of the rearranged products 18 and 19 were elucidated by X-ray crystal structure analysis. The oxazolo-isoquinoline trans-18 with allyl moiety (Ki = 89 nM) and the oxazolo-benzazepine 5 without substituent at the oxazolone ring (Ki = 114 nM) showed GluN2B affinity in the same range as the lead compound 3. In two-electrode voltage clamp measurements, 5 displayed only weak inhibitory activity.
Subject(s)
Phenol , Receptors, N-Methyl-D-Aspartate , Humans , Molecular Structure , Receptors, N-Methyl-D-Aspartate/metabolism , Structure-Activity Relationship , Oxazolone , Benzazepines/chemistry , Benzazepines/pharmacology , Alkylation , Phenols , Chromosome AberrationsABSTRACT
INTRODUCTION: Continuing education (CE) for pharmacists is mandatory in Germany. However, the findings on CE activities of pharmacists are limited. The aim of this study was to conduct a pilot survey on the CE situation of pharmacists in Germany, including licensed and future pharmacists, to determine the commitment to CE, the attitude towards CE and an obligation to provide evidence, the extent of CE considered necessary and the application of CE content in professional practice. METHODS: A cross-sectional study was conducted in the form of an online survey using SoSci survey, which was addressed to licensed pharmacists, pre-registration pharmacists, and pharmacy students. The online survey was promoted by pharmaceutical professional societies, trade media and interest groups. RESULTS: In total, 880 participants were included in the study: 695 pharmacists, 136 pharmacy students and 49 pre-registration pharmacists. Only 50.0% of the participants were aware of their CE obligations. Among the pharmacists, 44.9% reported that they held the voluntary advanced training certificate issued by the Chambers of Pharmacists. 551 participants reported the CE points of the past twelve month. On average, 56.2⯱â¯50.2 CE points were collected (xÌ â¯=â¯210.8 CE minutes per month). Pharmacists not holding the voluntary advanced training certificate of the Chamber of Pharmacists collected significantly fewer (pâ¯<â¯0.001) CE points (39.5⯱â¯32.0 points; xÌ â¯=â¯148.1 CE minutes per month). On average, the study population considered a minimum number of 33.9⯱â¯20.9 CE points per year (xÌ â¯=â¯127.1 CE minutes per month) to be adequate to meet the CE requirements. DISCUSSION: Although the majority participated in CE, the introduction of nationwide CE commitment monitoring was rejected. On the one hand, this may be linked to a lack of willingness to engage in lifelong learning. On the other hand, it should be borne in mind that, despite the same common nationwide legal basis, the different Chambers of Pharmacists districts have set up different rules concerning the minimum yearly CE commitment, the proof of compliance with CE requirements and fines for non-compliance. Therefore, the introduction of nationwide standard regulations may result in a greater acceptance of CE commitment checks. CONCLUSION: Pharmacists' willingness to CE participation has so far been dependent on intrinsic motivation. Although many licensed pharmacists were in possession of the advanced training certificate issued by the Chambers of Pharmacists, the majority of participants did not support the introduction of a nationwide CE commitment monitoring. 127.1 CE minutes per month were considered appropriate to fulfill the CE obligations, which is significantly less than the 187.5 CE minutes per month which are required to obtain the advanced training certificate of the Chambers of Pharmacists.
Subject(s)
Education, Pharmacy, Continuing , Pharmacists , Cross-Sectional Studies , Education, Continuing , Germany , Humans , Surveys and QuestionnairesABSTRACT
Reactive Sulfur Species (RSS), such as allicin from garlic or sulforaphane from broccoli, are fre-quently associated with biological activities and possible health benefits in animals and humans. Among these Organic Sulfur Compounds (OSCs) found in many plants and fungi, the Volatile Sulfur Compounds (VSCs) feature prominently, not only because of their often-pungent smell, but also because they are able to access places which solids and solutions cannot reach that easily. Indeed, inorganic RSS such as hydrogen sulfide (H2S) and sulfur dioxide (SO2) can be used to lit-erally fumigate entire rooms and areas. Similarly, metabolites of garlic, such as allyl methyl sulfide (AMS), are formed metabolically in humans in lower concentrations and reach the airways from inside the body as part of one's breath. Curiously, H2S is also formed in the gastrointestinal tract by gut bacteria, and the question of if and for which purpose this gas then crosses the barriers and enters the body is indeed a delicate matter for equally delicate studies. In any case, nature is surprisingly rich in such VSCs, as fruits (for instance, the infamous durian) demonstrate, and therefore these VSCs represent a promising group of compounds for further studies.