The study was designed to test the hypothesis that nitric oxide (NO)‐releasing compounds increase guanosine 3′:5′‐cyclic monophosphate (cyclic GMP) production in human polymorphonuclear leucocytes (PMNs) and concomitantly inhibit PMN functions, i.e. leukotriene B4 (LTB4) synthesis, degranulation, chemotaxis and superoxide anion (O2−) release. The effects of two new NO‐releasing compounds, GEA 3162 and GEA 5024 were compared to 3‐morpholino‐sydnonimine (SIN‐1) and S‐nitroso‐N‐acetyl‐penicillamine (SNAP). GEA 3162 and GEA 5024 (1–100 μm) inhibited Ca ionophore A23187‐induced LTB4 and β‐glucuronidase release, chemotactic peptide FMLP‐induced chemotaxis and opsonized zymosan‐triggered chemiluminescence dose‐dependently in human PMNs. SIN‐1 and SNAP were weaker inhibitors. Cellular cyclic GMP production was increased after exposure to NO‐donors concomitantly with the inhibition of PMN functions. No alterations in the levels of adenosine 3′:5′‐cylic monophosphate (cyclic AMP) were detected. The results suggest that NO, possibly through increased cyclic GMP, inhibits the activation of human PMNs and may thus act as a local modulator in inflammatory processes.
Two hundred and fifty-six sputum, bronchoalveolar lavage, and bronchial and tracheal aspirate specimens from 243 patients were tested for the presence of Mycobacterium tuberculosis complex by auramine fluorochrome staining, rRNA target amplification (Gen-Probe Amplified Mycobacterium Tuberculosis Direct Test [AMTD]), and PCR (Roche Amplicor Mycobacterium Tuberculosis Test [Amplicor PCR]). The results were compared with those of conventional Löwenstein-Jensen tube culture and BACTEC radiometric liquid culture. A total of 26 specimens from 18 patients were culture positive for M. tuberculosis. In addition, seven specimens were positive by staining and by culture for other Mycobacterium species but negative by nucleic acid amplification methods and were not included in the comparison. When compared with that for culture, the sensitivities of the techniques were as follows: for staining, 80.8%; for Gen-Probe AMTD, 84.6%; and for Roche Amplicor PCR, 84.6%. The specificities were 99.1, 98.7, and 99.1%, respectively. After resolution of discrepant results by review of the patients' clinical data, 29 specimens from 21 patients were considered positive, and the overall sensitivities, specificities, and positive and negative predictive values were 89.7, 100, 100, and 98.7% for culture; 75.9, 99.5, 95.7, and 96.9% for staining; 86.2, 100, 100, and 98.2% for Gen-Probe AMTD; and 82.8, 100, 100, and 97.9% for Roche Amplicor PCR, respectively. It is concluded that both nucleic acid amplification methods are rapid, sensitive, and specific methods for the detection of M. tuberculosis in respiratory specimens.
1 Vascular contractions induced by K+-free solution and relaxation responses following the return of K+ to the organ bath were studied in mesenteric arterial rings from spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY) with particular focus on the role of vascular adrenergic nerve-endings and endothelium. 2 In endothelium-denuded rings the omission of K+ from the incubation medium resulted in gradual contractions, the rate of which was slower in SHR than WKY. Nifedipine (1 ALM) inhibited the contractions more effectively in SHR than WKY. 3 Adrenergic denervation in vitro with 6-hydroxydopamine reduced the contractions induced by the K+-free medium in endothelium-denuded rings. The remaining contractions after denervation were markedly greater in SHR than WKY. 4 The presence of intact vascular endothelium attenuated the K+-free contractions in both strains, the attenuation being smaller in SHR than WKY. N0-nitro-L-arginine methyl ester (L-NAME, 0.1 mM) and methylene blue (10 fiM), but not indomethacin (10 JM), abolished the attenuating effect of endothelium on the K+-free contractions. L-Arginine (1 mM) reversed the effect of L-NAME in WKY but not in SHR. 5 The re-addition of K+ after full K+-free contractions dose-dependently relaxed the rings. The rate of this K+-induced relaxation was significantly slower in SHR than WKY at all K+ concentrations (0.1-5.9 mM) studied, whether the endothelium or functioning adrenergic nerve-endings were present or not. Ouabain (1 mM) totally inhibited the K+ relaxation in SHR but only partially in WKY. 6 Vascular smooth muscle contractions induced by high concentrations of potassium were comparable between the strains. The EC50 for noradrenaline-induced contractions was lower in SHR than WKY, but the maximal forces did not differ significantly. 7 In conclusion, the contractile response in K+-free solution more clearly differentiates vascular rings from SHR and WKY than the responses induced by the classical contractile agents noradrenaline and high concentrations of potassium. The depressant effect of the presence of intact endothelium on the K+-free contractions, which was smaller in SHR than WKY, is mediated via the endothelium-derived relaxing factor. Neurotransmitter release from vascular adrenergic nerve-endings participates less in the K+-free contractile response in SHR than WKY. Moreover, the contractile response is more dependent on calcium entry through nifedipine-sensitive calcium channels in SHR than WKY. The greater K+-free contractions of denervated endothelium-denuded rings and the reduced K+ relaxation rate in SHR when compared to WKY suggest increased cell membrane permeability and decreased activity of vascular Na+, K+-ATPase, respectively, in this type of genetic hypertension.
1 The nitric oxide (NO)-releasing properties of two new mesoionic 3-aryl substituted oxatriazole-5-imine derivatives (GEA 3162 and GEA 3175) were characterized and compared with the known NOdonors 3-morpholino-sydnonimine (SIN-1) and S-nitroso-N-acetylpenicillamine (SNAP). 2 GEA 3162, GEA 3175, SIN-i and SNAP inhibited adenosine 5'-diphosphate-induced platelet aggregation (IC50 values 0.18, 0.39, 3.73 and 2.12 gM, respectively). All four compounds induced a dosedependent and more than 4 fold increase in cyclic GMP in platelets. The increase in cyclic GMP concentration was potentiated more than 1.5 fold by a phosphodiesterase inhibitor, zaprinast (10 gM) and inhibited 38-97% by oxyhaemoglobin (10-45 gM).3 All of the four compounds studied converted oxyhaemoglobin to methaemoglobin and formed a paramagnetic NO-haemoglobin complex. All but GEA 3175 formed nitrite and nitrate in phosphate buffer. During a 40 min incubation, GEA 3162, SIN-I and SNAP (100 pM) produced 50-70 gM NO2-+ NO3-as determined by high performance liquid chromatography. The release of NO and NO2 by GEA 3175 was increased 140 fold in the presence of human plasma (0.14 and 19.7 ppb in the absence and presence of 1% human plasma, respectively) as analyzed by ozone chemiluminescence. 4 The results suggest that the mesoionic 3-aryl substituted oxatriazole-5-imine derivatives GEA 3162 and GEA 3175 as well as SIN-l and SNAP release nitric oxide.
Background Massive infusions of crystalloids into bleeding hypotensive patients can worsen the outcome. Military experience suggests avoiding crystalloids using early damage control resuscitation with blood components in out of hospital setting. Civilian emergency medical services have since followed this idea. We describe our red blood cell protocol in helicopter emergency medical services (HEMS) and initial experience with prehospital blood products from the first 3 years after implementation. Methods We performed an observational study of patients attended by the HEMS unit between 2015 and 2018 to whom packed red blood cells, freeze-dried plasma, or both were transfused. The Student’s two-sided T-test was used to compare vitals in prehospital phase with those at the hospital’s emergency department. A p -value < 0.05 was considered significant. Results Altogether, 62 patients received prehospital transfusions. Of those, 48 (77%) were trauma patients and most ( n = 39, 81%) suffered blunt trauma. The transfusion began at a median of 33 (IQR 21–47) minutes before hospital arrival. Median systolic blood pressure showed an increase from 90 mmHg (IQR 75–111 mmHg) to 107 mmHg (IQR 80–124 mmHg; P < 0.026) during the prehospital phase. Four units of red blood cells were handled incorrectly when unused red blood cells were returned and required disposal during a three-year period. There were no reported adverse effects from prehospital transfusions. Conclusion We treated two patients per month with prehospital blood products. A prehospital physician-staffed HEMS unit carrying blood products is a feasible and safe method to start transfusion roughly 30 min before arrival to the hospital. Trial registration The study was retrospectively registered by the Tampere University Hospital’s Medical Director (R19603) 5.11.2019.
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