Cocaine use in trauma: the vices-paradox revisited.

BACKGROUND: The "vices-paradox" describes the paradoxical association between illicit substance use and decreased mortality risk in trauma patients. Cocaine's vasoconstrictive effects may decrease hemorrhage but also increase the risk of thromboembolic complications. To clarify the effects of cocaine use on trauma patients, we compared the risk of mortality and thromboembolic complications in patients screening positive for cocaine with those screening negative. METHODS: We searched the Trauma Quality Improvement Program database to identify patients 18 years and over who had presented with a drug and alcohol screen on admission between 2017 and 2019. After excluding all patients who had tested positive for alcohol and substances other than cocaine, we then compared the clinical outcomes of patients who were positive and negative for cocaine use. RESULTS: Of the 312,553 patients identified, 11,942 (3.82%) had tested positive for cocaine. Cocaine users were significantly more likely to present with stab (8.0% vs 3.1%) or gunshot wounds (8.0% vs 3.0%) but had lower rates of mortality (3.6% vs 4.7%), myocardial infarction (0.1% vs 0.2%,) and cerebrovascular accident (0.3% vs 0.4%,). After controlling for covariates, the risk of death, myocardial infarction, and cerebrovascular accident did not significantly differ between cocaine and non-cocaine users. CONCLUSION: Trauma patients positive for cocaine have similar risks of death and thromboembolic complications and so have a similar prognosis to patients negative for all drugs or alcohol, indicating that the "vices-paradox" does not apply to cocaine use. However, these patients more commonly present after penetrating trauma, suggesting cocaine use in hazardous environments.

[Chronic cough]. / Chronischer Husten.

Coughing is an important protective reflex of the respiratory tract and primarily serves clearance of the bronchial system. It is also an exceptionally common symptom in outpatient care that can be an expression of a variety of diseases. Coughing duration of longer than 8 weeks is referred to as chronic cough. A structured, often interdisciplinary diagnostic process is essential. The aim here is to identify causal treatment options, avoiding overdiagnosis and simultaneously not overlooking severe illness. This article discusses current diagnostic procedures, important differential diagnoses and possible treatment options.

Purple Prairie Clover (Dalea purpurea Vent) Reduces Fecal Shedding of Escherichia coli in Pastured Cattle.

A 3-year (2009 to 2011) grazing study was conducted to assess the effects of purple prairie clover (PPC; Dalea purpurea Vent) on fecal shedding of total Escherichia coli in cattle. Three pasture types were used in the experiment: bromegrass (Check), mixed cool season grasses with PPC (Simple), and mixed cool and warm grasses with PPC (Complex). Pastures were rotationally grazed during a summer and fall grazing period. PPC was grazed in summer at the vegetative or early flower stage and at the flower or early seed stage during the fall. Fecal samples were collected for enumeration of E. coli and chemical analyses. Forage samples were collected throughout grazing for analysis. Condensed tannins (CT) were only detected in Simple and Complex pastures that contained PPC, with higher concentrations found in the fall than in the summer. Fecal counts of E. coli in cattle grazing Simple and Complex pastures linearly decreased (P < 0.05) over summer to fall in all 3 years, an outcome not observed in cattle grazing the Check pasture. Across the three grazing seasons, fecal E. coli was lower (P < 0.05) in cattle grazing Simple and Complex pastures than in those grazing the Check pasture during the fall. During the fall, feces collected from cattle grazing the Check pasture had higher (P < 0.05) values for pH, N, NH3-N, total volatile fatty acids, and branched-chain volatile fatty acids, but a lower (P < 0.05) acetate:propionate ratio than feces collected from cattle grazing Simple or Complex pastures. In a second experiment, two strains of E. coli were cultured in M9 medium containing 25 to 200 µg/ml of PPC CT. Growth of E. coli was linearly (P < 0.01) reduced by increasing levels of PPC CT. Scanning electron micrographs showed electron-dense filamentous material associated with the outer membrane of E. coli cells exposed to CT. Incorporation of PPC into forage reduced the fecal shedding of E. coli from grazing cattle, likely due to the anti-E. coli properties of PPC CT.

[Respiratory therapy with Ez-PAP for treatment of dynamic hyperinflation in patients with severe COPD and emphysema]. / Atemtherapie mit Ez-PAP zur Behandlung der dynamischen Überblähung bei Patienten mit schwerer COPD und Lungenemphysem.

BACKGROUND: Non-pharmacological respiratory physiotherapy in treatment of COPD with severe emphysema is achieving increasing importance. Ez-PAP, a compact CPAP- or flow-PEP system, supports inspiration by using the Coanda effect in addition to a PE(E)P-effect during expiration. METHODS AND PATIENTS: 30 patients with severe COPD and emphysema and hypercapnic respiratory failure under non-(NIV) (n = 28) and invasive ventilation (n = 2) were treated in ventilator-free intervals with Ez-PAP and analyzed retrospectively. Clinical courses such as ventilator-dependency, dyspnea by visual CR-10 Borg scale, results of six-minute walk tests (6MWT), lung function tests and recordings of transcutaneous CO2 measurements were evaluated where possible. RESULTS: Analyzed patients showed less ventilator dependancy (n = 9), reported a median decrease of shortness of breath by 3,3 points (n = 10) and improved by 50,4 m in the 6MWT (n = 5). A median increase of vital capacity by 544 ml (n = 5) was shown by spirometry. Combined with manual techniques for reducing air-trapping, treatment success was documented by a median reduction of pCO2 by 7,3 mmHg (n = 6) using transcutaneous pCO2 measurement. CONCLUSION: Ez-PAP is a simple mechanical method to reduce dynamic hyperinflation in severe COPD, thus achieving relief of respiratory muscles and more effective breathing. Prospective studies of this promising method are urgently required.

Activities of cholic acid-derived antimicrobial agents against multidrug-resistant bacteria.

Cationic cholic acid derivatives displayed potent and broad-spectrum activity against multidrug-resistant Gram-negative and -positive bacteria. Specific examples were effective permeabilizers of the outer membranes of many strains of multidrug-resistant Gram-negative bacteria and sensitized these to hydrophobic antibiotics. We also prepared a new cholic acid derivative with improved apparent selectivity for prokaryote membranes.

Production of ochratoxin A by Aspergillus carbonarius on coffee cherries.

Robusta coffee cherries collected before and during sun drying from two coffee farms in Thailand were examined for moulds producing ochratoxin A (OA). Aspergillus ochraceus was only detected in one sample, whereas Aspergillus carbonarius was isolated from 7 out of 14 samples. On gamma-irradiated coffee cherries, each of the six tested A. carbonarius strains produced OA. More than 4800 microg kg(-1) of toxin were detected under optimal conditions (25 degrees C, a(w) 0.99). OA production was strongly reduced (230 microg kg(-1)) at an a(w) of 0.94.

Partial Purification and Characterization of Red Chlorophyll Catabolite Reductase, a Stroma Protein Involved in Chlorophyll Breakdown.

Red chlorophyll (Chl) catabolite (RCC) reductase, which catalyzes the reaction of an intermediary Chl catabolite (RCC) in the two-step cleavage reaction of pheophorbide (Pheide) a into primary fluorescent catabolites (pFCCs) during Chl breakdown, was characterized and partially purified. RCC reductase activity was present at all stages of barley leaf development and even in roots. The highest specific activity was found in senescent leaves, which were used to purify RCC reductase 1000-fold. Among the remaining three proteins, RCC reductase activity was most likely associated with a 55-kD protein. RCC reductase exhibited saturation kinetics for RCC, with an apparent Michaelis constant of 0.6 mM. The reaction depended on reduced ferredoxin and was sensitive to oxygen. Assays of purified RCC reductase with chemically synthesized RCC as a substrate yielded three different FCCs, two of which could be identified as the stereoisomeric pFCCs from canola (Brassica napus) (pFCC-1) and sweet pepper (Capsicum annuum) (pFCC-2), respectively. In the coupled reaction with Pheide a oxidase and RCC reductase, either pFCC-1 or pFCC-2 was produced, depending on the plant species employed as a source of RCC reductase. Data from 18 species suggest that the stereospecific action of RCC reductase is uniform within a plant family.

How plants dispose of chlorophyll catabolites. Directly energized uptake of tetrapyrrolic breakdown products into isolated vacuoles.

During the yellowing of leaves the porphyrin moiety of chlorophyll is cleaved into colorless linear tetrapyrrolic catabolites, which eventually are deposited in the central vacuoles of mesophyll cells. In senescent cotyledons of rape, Brassica napus, three nonfluorescent chlorophyll catabolites (NCCs), accounting for practically all the chlorophyll broken down, were found to be located in the vacuoles (vacuoplasts) prepared from protoplasts. Transport of catabolites across the tonoplast was studied with vacuoles isolated from barley mesophyll protoplasts in conjunction with a radiolabeled NCC, Bn-NCC-1, prepared from senescent rape cotyledons. The uptake of Bn-NCC-1 into vacuoles was against a concentration gradient and strictly dependent on MgATP and it followed saturation kinetics with a Km of approximately 100 microM. Although the hydrolysis of ATP was required, transport was apparently independent of the vacuolar proton pumps: accumulation of the NCC occurred both in the presence of the H+-ATPase inhibitor bafilomycin and after destroying the DeltapH between the vacuolar sap and the medium. ATP could be replaced by GTP or UTP, and the transport was inhibited in the presence of vanadate. Chlorophyll catabolites isolated from senescent barley leaves competed with the rape-specific substrate for uptake into the vacuoles. Compounds such as the glutathione conjugate of N-ethylmaleimide and taurocholate, which are known to be transported across the tonoplast in a primary active mode, did not significantly inhibit uptake of Bn-NCC-1. Although the heme catabolites biliverdin and bilirubin inhibited the uptake of the NCC, this effect is caused by unspecific binding to the vacuolar membrane rather than to the specific inhibition of carrier-mediated transport. Taken together, the results demonstrate that barley mesophyll vacuoles are constitutively equipped with a directly energized carrier that transports tetrapyrrolic catabolites of chlorophyll into the vacuole.

Cleavage of Chlorophyll-Porphyrin (Requirement for Reduced Ferredoxin and Oxygen).

The chemical structures of some colorless catabolites that accumulate in senescent leaves have been established recently (B. Krautler, B. Jaun, W. Amrein, K. Bortlik, M. Schellenberg, P. Matile [1992] Plant Physiol Biochem 30: 333-346; W. Muhlecker, B. Krautler, S. Ginsburg, P. Matile [1993] Helv Chim Acta 76: 2976-2980). Such studies suggest that oxygenolytic cleavage of chlorophyll-porphyrin may occur by the action of a dioxygenase. We have attempted to demonstrate such an enzyme activity and to explore the requirements of the cleavage reaction in a reconstituted system of chloroplast (Chlpl) components prepared from senescent rape (Brassica napus L.) cotyledons. Intact senescent Chpls (also referred to as gerontoplasts) contain small amounts of two fluorescent chlorophyll catabolites, Bn-FCC-1 and Bn-FCC-2, probably representing primary cleavage products. Upon the incubation of Gpls in the presence of glucose-6-phosphate (Glc6P) or ATP, these catabolites (predominantly FCC-1) were produced in organello. In a reconstituted system of thylakoids and stroma fraction the FCCs (predominantly FCC-2) were produced in the presence of ferredoxin (Fd) and cofactors (NADPH, Glc6P) helping to keep Fd in the reduced state. Reduced Fd could not be replaced by other electron donors, suggesting that the putative dioxygenase requires Fd for the operation of its redox cycle. Production of FCC-2 did not occur in the absence of oxygen and it was inhibited by chelators of Fe2+. The contributions to the production of FCCs from both parts of the reconstituted system, thylakoids and stroma, are heat labile. The enzymic process in the thylakoids yields pheophorbide a, the presumptive precursor of FCCs. However, native senescent thylakoids could not be replaced as a "substrate" by free pheophorbide a. The stromal enzyme appears to have an affinity for senescent thylakoids; thus, "loaded" thylakoids capable of FCC production in the presence of Fd and cofactors were obtained upon homogenization of senescent cotyledons in a medium containing sorbitol and ascorbate. Such thylakoids were inactive if prepared from mature green cotyledons. As senescence was induced, the capacity to generate FCCs appeared and peaked when about half of the chlorophyll had disappeared from the cotyledons. The effectiveness of a relevant inhibitor showed that cytoplasmic protein synthesis was required for inducing the catabolic machinery in the loaded thylakoids. Thylakoids from mature Chlpls were ineffective as substrate of the stromal enzyme prepared from Gpls. However, senescent thylakoids yielded FCCs if challenged with stroma from either Chlpls or Gpls. Therefore, the stromal part of the system is likely to be a constitutive enzyme, and the pace-setting step of the pathway of chlorophyll breakdown seems to be located in the thylakoids.

Production and release of a chlorophyll catabolite in isolated senescent chloroplasts.

A non-green catabolite of chlorophyll (Chl) the fluorescent compound FC 2, is produced when intact senescent chloroplasts of barley (Hordeum vulgare L.) are incubated in the presence of ATP. The origin of FC 2 has now been demonstrated by employing senescent chloroplasts containing Chl (14)C-labelled in the pyrrole-rings: upon incubation in the presence of ATP, (14)C-labelled FC 2 is generated. The production of FC 2 requires the hydrolysis of ATP as demonstrated by the failure of the ß, γ-imido analogue to support the reaction. Adenosine triphosphate can partially be replaced by UTP but GTP and CTP, as well as ADP and AMP, are ineffective. The system responsible for FC 2 production can also be fueled with glucose-6-phosphate, fructose-6-phosphate and glucose-1-phosphate; other sugar-phosphates including glyceraldehyde-3-phosphate have no effect. Adenosine triphosphate is also required for the release of FC 2 from chloroplasts. When chloroplasts are incubated in the presence of UTP or hexose-monophosphates which support the generation of FC 2 within the organelles, the catabolite is not released. It is concluded that the envelope of senescent chloroplasts is equipped with translocators for the cytosolic compounds which provide the metabolic energy and cofactors required for the action of the catalyst(s) responsible for the oxidative cleavage of Chl-porphyrin and possibly also for the dismantling of Chl-protein complexes. Moreover, a translocator may be involved in the release of the primary catabolites of Chl from chloroplasts.

Catabolites of chlorophyll in senescing barley leaves are localized in the vacuoles of mesophyll cells.

Senescing barley leaves accumulate a series of pink pigments with the chemical properties of catabolites derived from chlorophyll. Levels of the major component of this group of pigments were quantified by HPLC and shown to be maximal in tissues exhibiting maximal rates of chlorophyll degradation. Protoplasts were isolated from senescent leaf tissue and fractionated to yield intact vacuoles and plastids. Although small but significant proportions both of total catabolites and of the dominant component of the series were recovered from the plastid fraction, the vast bulk of these compounds could be assigned to the vacuole. These observations suggest a role for the vacuole in the later stages of chlorophyll breakdown during senescence.

Does a cyclic AMP-dependent phosphorylation initiate the transfer of trehalase from the cytosol into the vacuoles in Saccharomyces cerevisiae?

Trehalase activity in a yeast protoplast lysate increased approximately 40-times upon preincubation with cAMP and ATP. The activity present without the preincubation could all be sedimented at 8000 x g, for 10 min confirming the previously reported localization of the active trehalase (Ta) in the vacuoles. Virtually all the trehalase activity newly formed upon the preincubation, however, was found in the soluble fraction, indicating that a trehalase-zymogen (Tz) is located in the cytosol. This raises the possibility that a cAMP-dependent phosphorylation not only transforms Tz to Ta but also initiates the transfer of trehalase from the cytosol into the vacuoles.

Localization of trehalase in vacuoles and of trehalose in the cytosol of yeast (Saccharomyces cerevisiae).

Protoplasts of Saccharomyces cerevisiae synthesized and degraded trehalose when they were incubated in a medium containing traces of glucose and acetate. Such protoplasts were gently lyzed by the polybase method and a particulate and soluble fraction was prepared. Trehalose was found in the soluble fraction and the trehalase activity mostly in the particulate fraction which also contained the vacuoles besides other cell organelles. Upon purification of the vacuoles, by density gradient centrifugation, the specific activity of trehalase increased parallel to the specific content of vacuolar markers. This indicates that trehalose is located in the cytosol and trehalase in the vacuole. It is suggested that trehalose, in addition to its role as a reserve may also function as a protective agent to maintain the cytosolic structure under conditions of stress.