Examining outpatients' hand hygiene behaviour and its relation to COVID-19 infection prevention measures.

BACKGROUND: The increasing demand for outpatient care is associated with a higher risk of infection transmission in these settings. However, there is limited research on infection prevention and control practices in ambulatory clinics, and none focuses on patients. AIM: To examine outpatients' hand hygiene behaviours, their determinants, and their associations with other infection prevention measures during the COVID-19 pandemic. METHODS: We observed the hand hygiene behaviour of one cohort of patients in one outpatient clinic and surveyed a separate sample in five clinics about their hand hygiene practice in outpatient facilities. A questionnaire based on the Theoretical Domains Framework (TDF) was used to examine predictors of the behaviour. Moreover, patients indicated their compliance with COVID-19 infection prevention measures, vaccination status, disease risk perception, and vaccine hesitancy. FINDINGS: Observed hand hygiene rates among 618 patients were low (12.8%), while 67.3% of the 300 surveyed patients indicated sanitizing their hands upon entering the clinic. The TDF domains 'memory, attention, and decision processes' and 'emotions' significantly predicted both current (today's) and general hand hygiene behaviour in outpatient clinics. Hand hygiene behaviour and compliance with COVID-19 infection prevention showed a positive association; however, no significant connection was found with patients' vaccination status, suggesting different behavioural motivators. CONCLUSION: Hand hygiene among outpatients should be improved through interventions focusing on helping patients remember to clean their hands. More research on infection prevention in outpatient facilities is needed to ensure patient safety.

Investigations on aviadenoviruses isolated from turkey flocks in Germany.

During routine diagnosis in 2012, 69 samples of diseased turkey breeding and fattening flocks in Germany were examined for infection with aviadenoviruses by virus isolation using primary chicken embryo liver cells. In total, 21 aviadenovirus isolates, identified by a group-specific indirect immunofluorescence test, were obtained from 19 flocks. In almost all cases, molecular typing of these isolates based on partial hexon gene sequences revealed the presence of different types of turkey aviadenoviruses (TAdVs), including species Turkey aviadenovirus B (TAdV-B) with at least two different genotypes, as well as the species Turkey aviadenovirus C (TAdV-C) and Turkey aviadenovirus D (TAdV-D). Further analysis of DNA-dependent DNA polymerase gene sequences confirmed the classification of selected TAdV-C and TAdV-D isolates. Based on the results obtained for both genes, we suggest that TAdV-2, in addition to TAdV-4, belongs to the species TAdV-C. In contrast, amplification of the DNA polymerase gene fragment of nearly all investigated TAdV-B isolates failed due to unknown reasons. The results of sequence and phylogenetic analysis support the previously proposed classification of TAdVs into three different species and demonstrated how widely spread these viruses are in German turkey flocks. Analysis of case histories revealed a wide range of clinical and pathological changes; however an apparent link between types and disease conditions was not identified.

Magnetic field and contact resistance dependence of non-local charge imbalance.

Crossed Andreev reflection (CAR) in metallic nanostructures, a possible basis for solid-state electron entangler devices, is usually investigated by detecting non-local voltages in multi-terminal superconductor/normal metal devices. This task is difficult because other subgap processes may mask the effects of CAR. One of these processes is the generation of charge imbalance (CI) and the diffusion of non-equilibrium quasi-particles in the superconductor. Here we demonstrate a characteristic dependence of non-local CI on a magnetic field applied parallel to the superconducting wire, which can be understood by a generalization of the standard description of CI to non-local experiments. These results can be used to distinguish CAR and CI and to extract CI relaxation times in superconducting nanostructures. In addition, we investigate the dependence of non-local CI on the resistance of the injector and detector contacts and demonstrate a quantitative agreement with a recent theory using only material and junction characteristics extracted from separate direct measurements.

Continuous 48-h C1-inhibitor treatment, following reperfusion therapy, in patients with acute myocardial infarction.

AIMS: Complement inhibition by C1-inhibitor has been shown to reduce myocardial ischaemia-reperfusion injury in animal models. We therefore studied the effects of intravenous C1-inhibitor, following reperfusion therapy, in patients with acute myocardial infarction. METHODS AND RESULTS: C1-inhibitor therapy was started not earlier than 6h after acute myocardial infarction, in order to prevent interference with thrombolytic therapy. A loading dose of C1-inhibitor was followed by a continuous infusion for 48 h, using three escalating dosage schemes. Efficacy of complement inhibition was estimated from C4 activation fragments. Plasma concentrations of myocardial proteins were compared to values measured in matched control patients. In 22 patients, C1-inhibitor was well tolerated and drug-related adverse events were not observed. Target plasma levels of C1-inhibitor were reached, with values of 48.2 ml.kg(-1) for distribution space and 35.5h for the half-life time of C1-inhibitor. A dose-dependent reduction of C4 fragments was found P=0.005). In 13 patients who received early thrombolytic therapy, release of troponin T and creatine kinase-MB(mass) was reduced by 36% and 57%P =0.001), compared to 18 controls. CONCLUSION: Continuous 48-h treatment with C1-inhibitor provides safe and effective inhibition of complement activation after reperfused acute myocardial infarction and may reduce myocardial injury.

Effect of acute phase response on cumulative troponin T release.

UNLABELLED: We studied a possible effect of the extent of the acute phase response after acute myocardial infarction on the cumulative release of troponin T. The height of the acute phase response might influence the cumulative release of troponin T, bound to the myofibrillar structures of the heart, in a different way compared to the free cytoplasmic cardiac marker hydroxybutyrate dehydrogenase (EC 1.1.1.27). To investigate this, the cumulative amount of C-reactive protein in plasma, i.e. the quantified acute phase response, was related to the cumulative plasma release of hydroxybutyrate dehydrogenase (an established method for infarct sizing) on the one hand and to that of troponin T on the other hand. The study was performed in patients receiving (n=16) and in patients not receiving (n=6) thrombolytic therapy. Cumulative protein release was calculated using a two-compartment model for circulating proteins. CONCLUSIONS: The cumulative amount of plasma C-reactive protein is significantly higher in the patients not receiving thrombolytic therapy, as is in accordance with earlier studies. The cumulative amount of troponin T released is significantly related to the cumulated concentration of C-reactive protein, especially in patients not receiving thrombolytic therapy. The intensity of the acute phase response, estimated from cumulative plasma C-reactive protein response, has no effect on the relative proportions of troponin T and hydroxybutyrate dehydrogenase released into plasma.

Discrimination between myocardial and skeletal muscle injury by assessment of the plasma ratio of myoglobin over fatty acid-binding protein.

BACKGROUND: Myoglobin and fatty acid-binding protein (FABP) each are useful as early biochemical markers of muscle injury. We studied whether the ratio of myoglobin over FABP in plasma can be used to distinguish myocardial from skeletal muscle injury. METHODS AND RESULTS: Myoglobin and FABP were assayed immunochemically in tissue samples of human heart and skeletal muscle and in serial plasma samples from 22 patients with acute myocardial infarction (AMI), from 9 patients undergoing aortic surgery (causing injury of skeletal muscles), and from 10 patients undergoing cardiac surgery. In human heart tissue, the myoglobin/FABP ratio was 4.5 and in skeletal muscles varied from 21 to 73. After AMI, the plasma concentrations of both proteins were elevated between approximately 1 and 15 to 20 hours after the onset of symptoms. In this period, the myoglobin/FABP ratio was constant both in subgroups of patients receiving and those not receiving thrombolytics and amounted to 5.3 +/- 1.2 (SD). In serum from aortic surgery patients, both proteins were elevated between 6 and 24 hours after surgery; the myoglobin/FABP ratio was 45 +/- 22 (SD), which is significantly different from plasma values in AMI patients (P < .001). In patients with cardiac surgery, the ratio increased from 11.3 +/- 4.7 to 32.1 +/- 13.6 (SD) during 24 hours after surgery, indicating more rapid release of protein from injured myocardium than from skeletal muscles. CONCLUSIONS: The ratio of the concentrations of myoglobin over FABP in plasma from patients with muscle injury reflects the ratio found in the affected tissue. Since this ratio is different between heart (4.5) and skeletal muscle (20 to 70), its assessment in plasma allows the discrimination between myocardial and skeletal muscle injury in humans.

Effect of pyridostigmine pretreatment on cardiorespiratory function in tabun poisoning.

1. The effect of pyridostigmine on cardiorespiratory function after oxime + atropine injection was investigated in tabun poisoned guinea-pigs and without tabun poisoning. 2. The trachea, a carotid artery and jugular vein were cannulated in female urethane-anaesthetised Pirbright-white guinea-pigs. After baseline measurements the animals received pyridostigmine (0.05 mumol kg-1) and 30 min later atropine (29.5 mumol kg-1) plus obidoxime, HI 6 or HLö 7 (30 or 100 mumol kg-1) or tabun (1.85 mumol kg-1 = 5 x LD50) followed by oxime + atropine treatment (all i.v.). Erythrocyte, brain and diaphragm acetylcholinesterase (AChE) activity were determined. Similar groups without pretreatment were included for comparison. 3. Pyridostigmine aggravated the oxime + atropine induced hypotension and prevented the increase in heart rate but not the respiratory stimulation. The pyridostigmine inhibited AChE recovered only in the 100 mumol kg-1 kg oxime groups at the end of the experiment. 4. In tabun poisoning, pyridostigmine reduced the oxime + atropine induced circulatory recovery and decreased the survival time and rate. It did not affect the therapeutic oxime + atropine effect on respiratory function. 5. These results suggest that pyridostigmine enhances oxime + atropine related circulatory depression which may be the reason for the reduced efficacy of oxime + atropine treatment in tabun poisoning. The possible mechanisms are discussed.

Antidotal efficacy of newly synthesized dimercaptosuccinic acid (DMSA) monoesters in experimental arsenic poisoning in mice.

The efficacy of four newly synthesized monoesters of meso-2,3-dimercaptosuccinic acid (DMSA), mono-i-amyl- (Mi-ADMS), mono-n-amyl- (Mn-ADMS), mono-i-butyl- (Mi-BDMS), and mono-n-butyl-meso-2,3-dimercaptosuccinate (Mn-BDMS) in increasing survival and arsenic elimination in experimental arsenic poisoning was investigated. Male mice (strain NMRI) received arsenite sc (survival study: 130 mumol/kg, 7 mice/group; elimination study: 85 mumol/kg (LD5) together with a tracer dose of 73As(III), 6 mice/group). After 30 min mice were treated with 0.7 mmol/kg of DMSA or a monoester ip or via gastric tube (ig). Control animals received saline ip. In the survival study mice were observed for 30 days. In the elimination study, the 73-arsenic content of several organs (blood, liver, heart, lung, kidneys, spleen, testes, brain, small intestine, large intestine, muscle, and skin) was measured 0.5, 2, 4, 6, and 8 hr after the arsenic injection using a gamma counter. Survival increased correspondingly well with the increase of arsenic elimination. DMSA, Mi-ADMS, Mn-ADMS, Mi-BDMS, and Mn-BDMS markedly decreased arsenic content in most organs as soon as 1.5 hr after treatment. Only in small and large intestine were higher arsenic amounts found, indicating a shift in arsenic elimination from the renal to the fecal route, and thereby suggesting a protective effect for the kidneys. Given ip, the monoesters turned out to be similarly as effective as the parent drug DMSA. Following ig treatment, the DMSA monoesters Mi-ADMS and Mn-ADMS seemed to be superior to DMSA with regard to survival.(ABSTRACT TRUNCATED AT 250 WORDS)

Arrhythmias in organophosphate poisoning: effect of atropine and bispyridinium oximes.

The effect of atropine and of the bispyridinium oximes, HI6 and HLö 7, on the electrocardiographic pattern was investigated in acutely nerve agent-poisoned guinea-pigs. The electrocardiographic, circulatory and respiratory parameters were recorded in female urethane-anaesthetized Pirbright-white guinea-pigs. After base line measurements, the animals received pyridostigmine (0.05 mumol/kg) and, 30 min later, tabun (5xLD50), sarin (5xLD50), soman (5xLD50 or 10xLD50) or VX (10xLD50 or 20xLD50), followed by saline or atropine (10 mg/kg) or atropine plus HI 6 or or HLö 7 (30 mumol/kg) 2 minutes later. Nerve agent poisoning resulted in respiratory arrest within 2-3 minutes, followed by circulatory arrest a few minutes later in nontreated animals. Antidote treatment rapidly restored heart rate and mean arterial pressure and improved the respiratory function to various extent. The nerve agent injection caused a marked sinus bradycardia and a subsequent complete atrioventricular block within 1-2 minutes, followed by idioventricular rhythm. No ventricular tachyarrhythmias were observed in these groups just before death. Atropine and atropine plus oxime administration immediately restored sinus rhythm which persisted in animals with sufficient respiration > 50% of base line) throughout the observation period (60 minutes). In guinea-pigs with depressed respiratory function ( < 50%), intermittent ST-T wave alterations and second degree atrioventricular block were observed. In some cases, especially in tabun and soman (10xLD50) poisoning, sinus rhythm converted to deleterious ventricular tachycardia within 1 minute after treatment. These results suggest that atropine-containing antidote combinations may induce lethal arrhythmias in nerve agent poisoning, which may be of clinical importance during intravenous treatment of severe inhalative intoxications.

Histochemical localization of heart-type fatty-acid binding protein in human and murine tissues.

Cellular fatty acid-binding proteins (FABP) are a highly conserved family of proteins consisting of several subtypes, among them the mammary-derived growth inhibitor (MDGI) which is quite homologous to or even identical with the heart-type FABP (H-FABP). The FABPs and MDGI have been suggested to be involved in intracellular fatty acid metabolism and trafficking. Recently, evidence for growth and differentiation regulating properties of MDGI and H-FABP was provided. Using four affinity-purified polyclonal antibodies against bovine and human antigen preparations, the cellular localization of MDGI/H-FABP in human and mouse tissues and organs was studied. The antibodies were weakly cross-reactive with adipose tissue extracts known to lack H-FABP, but failed to react by Western blot analysis with liver-type FABP (L-FABP) and intestinal-type FABP (I-FABP). MDGI/H-FABP protein was mainly detected in myocardium, skeletal and smooth muscle fibres, lipid and/or steroid synthesising cells (adrenals, Leydig cells, sebaceous glands, lactating mammary gland) and terminally differentiated epithelia of the respiratory, intestinal and urogenital tracts. The results provide evidence that expression of H-FABP is associated with an irreversibly postmitotic and terminally differentiated status of cells. Since all the antisera employed showed spatially identical and qualitatively equal immunostaining, it is suggested that human, bovine and mouse MDGI/H-FABP proteins share highly homologous epitopes.

Fatty-acid-binding protein as a plasma marker for the estimation of myocardial infarct size in humans.

BACKGROUND: There are substantial amounts of cytoplasmic heart-type fatty-acid-binding protein (FABP) (15 kDa) in myocardial tissue. The rapid release of FABP into plasma during ischaemia indicates the possibility of using this protein as a biochemical marker for ischaemic myocardial injury. OBJECTIVE: To study the completeness of the release of FABP from damaged tissue in patients with acute myocardial infarction (AMI) and the suitability of serial plasma FABP concentrations for estimation of myocardial infarct size. METHODS: Immunochemically assayed FABP and enzymatically assayed creatine kinase isoenzyme MB (CK-MB) and alpha-hydroxybutyrate dehydrogenase (HBDH) were determined serially in plasma samples from 49 patients with AMI who had been treated with thrombolytic agents within six hours after the onset of AMI. Previously validated circulatory models and a value of 2.6 h-1 for the fractional clearance rate of FABP from plasma were used to calculate cumulative protein release into plasma. RESULTS: Release of FABP was completed earlier (24-36 h) after AMI than that of CK-MB (50-70 h) and that of HBDH (> 70 h). However, infarct size estimated from the cumulative release of the proteins and expressed as gram equivalents of healthy myocardium per litre of plasma yielded a comparable value of 4-6 for both FABP and the two enzymes. CONCLUSION: The data indicate that FABP released from the heart after AMI is quantitatively recovered in plasma and that FABP is a useful biochemical plasma marker for the estimation of myocardial infarct size in humans.

Stimulation of prostaglandin biosynthesis mediates gastroprotective effect of rebamipide in rats.

The concept that gastroprotection by agents such as mild irritants, antacids, or sucralfate is prostaglandin (PG)-mediated has been challenged recently. These agents do not reproducibly stimulate prostaglandin formation, and indomethacin does not effectively attenuate their protective potency. Rebamipide is a novel antiulcer compound. This study was designed to clarify whether eicosanoids contribute to the gastroprotective activity of the drug. In the rat stomach, rebamipide (100 and 500 mg/kg, intraperitoneally) slightly increased release of PGE2, 6-keto-PGF1 alpha, thromboxane B2, and the metabolite 15-keto-13,14-dihydro-PGE2 from mucosal fragments incubated ex vivo and significantly enhanced secretion of these products into the lumen, resulting in gastric juice eicosanoid levels exceeding those in controls several-fold. Mucosal formation of leukotriene (LT) C4 was not affected by rebamipide. Rebamipide caused substantial protection against gastric damage produced by ethanol, which was antagonized by pretreatment with indomethacin (0.1-5 mg/kg, subcutaneously). The dose-response relationship of indomethacin for inhibition of prostaglandin formation and rebamipide-induced protection correlated well and 5 mg/kg indomethacin completely prevented the protective effect of rebamipide. The results indicate that: (1) in contrast to most other protective agents, protection by rebamipide involves the endogenous prostaglandin system; (2) the increase in prostaglandin formation results from stimulation of biosynthesis, and not inhibition of degradation; (3) gastroprotection by rebamipide occurs despite increased thromboxane formation and is not associated with reduced generation of LTC4; and (4) determinations of gastric juice eicosanoids seem to be particularly useful to evaluate effects of agents increasing formation of cyclooxygenase products in the stomach.

Immunohistochemical detection of very recent myocardial infarctions in humans with antibodies against heart-type fatty acid-binding protein.

Depletion of human heart-type fatty acid-binding protein (H-FABP) from cardiomyocytes in infarcted areas with varying postinfarction intervals was studied in 25 autopsy cases. In 23 autopsy cases myocardial infarction was the clinical diagnosis; 2 cases were noncardiac deaths and served as controls. Formaldehyde-fixed and paraffin-embedded myocardial tissue sections were stained immunohistochemically with antibodies to human H-FABP. H-FABP immunohistochemical findings were compared with those from conventional nitroblue tetrazolium (NBT) macroenzyme staining and conventional histochemical hematoxylin-eosin staining of sections of the same infarctions. In all cases of infarction confirmed by NBT staining, decreased or absent H-FABP immunostaining was observed. In 12 cases of clinically diagnosed infarction, H-FABP depletion could be demonstrated in areas that showed normal NBT staining. These findings strongly suggest that immunohistochemical staining with antibodies to H-FABP can confirm the clinical diagnosis or suspicion of early myocardial infarction. In both control cases no depletion of H-FABP was observed in cardiomyocytes in different myocardial tissue sections, and macroenzyme staining with NBT was normal. We conclude that H-FABP immunostaining may detect very recent ischemia/ infarction in human myocardium and can be applied in routine autopsy pathology.

Release of heart fatty acid-binding protein into plasma after acute myocardial infarction in man.

The release of cytoplasmic heart fatty acid-binding protein (H-FABP) into the plasma of cardiac patients up to 38 hr after the onset of the first clinical symptoms of acute myocardial infarction (AMI) was studied, using a sensitive direct and noncompetitive Enzyme Linked Immunosorbent Assay of the antigen capture type (sandwich ELISA), newly developed for the measurement of small amounts of human H-FABP in plasma samples. Plasma levels of H-FABP were compared with plasma activity levels of the myocardial cytoplasmic enzymes creatine kinase MB (CK-MB) and alpha-hydroxybutyrate dehydrogenase (alpha-HBDH). Upper normal levels of H-FABP (19 micrograms/l), CK-MB (10 U/l) and alpha-HBDH (160 U/l) as determined in plasma from 72 blood donors served as threshold levels. H-FABP levels were significantly elevated above their threshold level within 3 hr after AMI. Peak levels of H-FABP, CK-MB and alpha-HBDH were reached 4.1 +/- 0.9 hr, 8.4 +/- 1.4 hr and 25.0 +/- 9.5 hr (means +/- S.D., n = 10) after acute myocardial infarction, respectively. Serial time curves of the plasma contents of H-FABP reveal that after myocardial infarction H-FABP is released in substantial amounts from human hearts. In 18 out of 22 patients with established AMI the plasma FABP level was at or above the threshold level in blood-samples taken within 3.5 hr after the first onset of symptoms of AMI, while for CK-MB this applied to 9 patients and for alpha-HBDH to 6 patients. These findings suggest that for an early indication of acute myocardial infarction in man cytoplasmic heart fatty acid-binding protein is more suitable than heart type creatine kinase MB and/or alpha-hydroxybutyrate dehydrogenase.

High-yield two-step chromatographic procedure for purification of fatty acid-binding protein from human heart.

A high-yield procedure for the purification of cytoplasmic fatty acid-binding protein from human heart (H-FABP) is described. H-FABP was purified by gel permeation chromatography on a Sephacryl S-200 column followed by anion-exchange chromatography on a Sepharose Q fast-flow column at pH 7.0. At this pH H-FABP binds strongly to the column and can be selectively eluted with a salt gradient. The two-step procedure showed a high degree of reproducibility. On average 50 mg of H-FABP was obtained from 150 g of human heart tissue, which corresponds to a recovery of about 50%. Purity was confirmed by gel electrophoresis and isoelectric focusing. Binding of oleic acid to purified H-FABP, using the Lipidex 1000 assay, revealed a maximal binding of 0.75 +/- 0.01 mol fatty acid/mol protein and a dissociation constant of 0.19 +/- 0.01 microM.

Type-specific immunodetection of human heart fatty acid-binding protein with polyclonal anti-peptide antibodies.

In order to develop specific antibodies against human heart cytoplasmic fatty acid-binding protein (H-FABPc), four oligo-peptides of 15-20 amino-acids each and corresponding with different antigenic parts of the human H-FABPc molecule, were synthesized. Polyclonal antibodies against these synthetic peptides were raised in mice (Balb/C) and rabbits (Flemish giant). When tested in enzyme linked immunosorbent assays (ELISA, antibody-capture assay), antisera against three of the four peptides showed a high immunoreactivity with the synthetic peptide selected for immunization as well as with the native human H-FABPc. Some cross-reactivity with the other synthetic peptides was observed for the rabbit antisera but not for those from mice. Polyclonal antibodies against synthetic peptides can be applied for the specific detection of the native protein in biological preparations containing proteins that show a high degree of homology with the protein to be assayed.

Gastrointestinal toxicity. Role of prostaglandins and leukotrienes.

Gastrointestinal tissues have a high synthesising capacity for prostaglandins. As exogenous prostaglandins protect the gastrointestinal mucosa against potentially noxious agents, it has been suggested that the generation of prostaglandins plays a crucial role in the maintenance of mucosal integrity. Analgesic and anti-inflammatory drugs with a potent inhibitory action on gastrointestinal cyclo-oxygenase, such as indomethacin, induce gastric and intestinal ulcerations in experimental animals and frequently lead to gastrointestinal side effects in man. However, drugs that do not reduce gastrointestinal prostaglandin formation, such as paracetamol (acetaminophen), are devoid of gastrointestinal toxicity. Various factors, e.g. tissue-specific differences in the sensitivity of cyclo-oxygenase against inhibition and pharmacokinetic properties, modify the inhibitory activity of analgesic and anti-inflammatory drugs on gastrointestinal prostaglandin formation. As leukotriene C4 is a potent gastric vasoconstrictor, increased metabolism of arachidonic acid via the 5-lipoxygenase pathway in the presence of inhibition of cyclo-oxygenase could possibly contribute to drug-induced gastrointestinal damage.