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The use of these drugs as sedative–hypnotic agents is almost obsolete discount oxybutynin 2.5mg mastercard, supplanted by ben- zodiazepines and other nonbenzodiazepine sedative–hypnotic agents 2.5 mg oxybutynin otc. Barbiturates produce dose-related respiratory depression with cerebral hypoxia purchase oxybutynin 2.5 mg visa, possibly leading to coma or death; this effect results from abuse or suicide attempt discount oxybutynin 5 mg. Treatment includes ventilation generic 5mg oxybutynin fast delivery, gastric lavage, hemodialysis, osmotic diuretics, and (for phenobarbital) alkalinization of urine. Phenobarbital and pentobarbital are occasionally used to treat the physical dependence associated with long-term use of sedative–hypnotic drugs. Conventional antipsychotic drugs are often subclassified according to their oral milligram potency (high potency or low potency). Other conventional heterocyclic antipsychotic drugs such as loxapine and molindone, with intermediate potency, have no clear advantage over other conventional drugs. The therapeutic action of the conventional antipsychotic drugs is correlated best with antago- nist activity at postjunctional dopamine D2-receptors, where dopamine normally inhibits adenylyl cyclase activity. Most of these drugs show little correlation between plasma levels and therapeutic action. Most antipsychotic drugs are highly lipophilic and have long half-lives (10–20 h). Thioridazine is metabolized to mesoridazine, which accounts for most of the parent compound’s effects. Esterification of fluphenazine and haloperidol (fluphenazine decanoate, haloperidol dec- anoate) results in long-acting depot forms (2- to 3-week duration of action) that can be used to 106 Pharmacology manage compliance issues. Plasma esterases convert the parent compound to the active drug when the ester diffuses into the bloodstream. However, their antipsychotic effects, including decreased symptoms of thought disorders, paranoid features, delusions, hostility, hallucinations (the positive symptoms of schizophrenia) and, to a lesser degree, decreased withdrawal, apathy, and blunted affect (the negative symptoms of schizophre- nia), typically take longer to occur (a week or more). Atypical antipsychotic drugs, particu- larly clozapine, have a seemingly greater effect on negative symptoms than the conventional agents. Tourette syndrome (haloperidol or pimozide [Orap]), to suppress severe tics and vocalization e. Severe nausea or vomiting associated with a variety of diseases, radiation treatment, and cancer chemotherapy, as well as postoperative nausea and vomiting. Conventional antipsy- chotic agents, with the exception of thioridazine, have strong antiemetic activity due to dopamine D2-receptor blockade in the chemoreceptor trigger zone of the medulla. The most commonly used are the phenothiazine prochlorperazine, which is marketed only as an antiemetic, and promethazine, which has no antipsychotic activity. Selection of a specific antipsychotic agent for therapeu- tic use is often based on its associated adverse effects rather than therapeutic efficacy. They are less likely to occur with low-potency conventional antipsychotic drugs such as thioridazine, which have lower affinity for dopamine D2-receptors than high-potency drugs. With the exception of risperidone, they are also unlikely to occur with atypical antipsychotic drugs such as clozapine and olanzapine. Extrapyramidal effects are also less likely to occur with those conventional agents that also have sub- stantial antagonist activity at cholinoceptors in the basal ganglia. Chapter 5 Drugs Acting on the Central Nervous System 107 table 5-3 Potency and Selected Adverse Effects of Representative Conventional Antipsychotic Drugs Extrapyramidal Autonomic Drugs Oral Dose (mg) Effectsa Effects Sedation Conventional drugs Aliphatic phenothiazines Chlorpromazine 100 ++ +++ +++ Triflupromazine 50 ++ +++ +++ Piperidine phenothiazines Thioridazineb,c 100 + +++ +++ Mesoridazinec 50 + +++ +++ Piperazine phenothiazines Trifluoperazine 10 +++ ++ ++ Fluphenazined 5 +++ ++ ++ Butyrophenones Haloperidol 2 +++ + + Other related drugs Molindonec 20–200 +++ ++ ++ Loxapine 20–250 +++ ++ ++ aExcluding tardive dyskinesia. Tardive dyskinesia (1) Tardive dyskinesia is much more likely with conventional antipsychotic agents than atypical agents. Neuroleptic malignant syndrome (1) Neuroleptic malignant syndrome is most likely in patients sensitive to the extrapyrami- dal effects of the conventional high-potency antipsychotic agents. Sedation (see Tables 5-3 and 5-4) (1) The sedation effects, more likely with low-potency antipsychotic agents and with the atypical agents, are due to a central histamine H1-receptor blockade. This effect is likely with antipsychotic agents with pronounced antimuscarinic activity. Seizures (1) Seizures are especially more common with chlorpromazine, clozapine, and olanzapine. Muscarinic cholinoceptor blockade (1) Blockade of muscarinic cholinoceptors, more common with conventional low-potency antipsychotic agents and with the atypical agent clozapine, produces an atropine-like effect, resulting in dry mouth and blurred vision. Endocrine and metabolic disturbances, likely with most conventional antipsychotic agents and the atypical agent risperidone, are due to dopamine (D2)-receptor antagonist activity in the pi- tuitary, resulting in hyperprolactinemia (see Table 5-4). In women, these disturbances include spontaneous or induced galactorrhea, loss of libido, and delayed ovulation and menstruation or amenorrhea. Weight gain, which is likely with most conventional antipsychotic agents and the atypical antipsychotic agents, clozapine and olanzapine, may be due in part to histamine H1-recep- tor antagonist activity (see Table 5-4). Withdrawal-like syndrome (1) This syndrome is characterized by nausea, vomiting, insomnia, and headache in 30% of patients, especially those receiving low-potency antipsychotic drugs. Cardiac arrhythmias (1) Cardiac arrhythmias result from a quinidine-like effect in which there is local anesthetic activity with an increased likelihood of heart block. Blood dyscrasias are rare, except in the case of clozapine, which may induce agranulocyto- sis in up to 3% of patients and, therefore, is used only when other drug groups prove ineffective.

If this is true discount 2.5mg oxybutynin with visa, it becomes difficult to read this statement as the propagation of a new theological doctrine order oxybutynin 2.5 mg with visa. Of the three factors mentioned generic oxybutynin 5 mg otc, the sun is least problematic oxybutynin 2.5mg for sale, since the divinity of the celestial bodies was hardly ever questioned throughout the classical period order 2.5mg oxybutynin, even in intellectual circles27 – although the focus of the text is not on the sun as a celestial body but rather on the heat it produces (see 10. The divinity of cold ( psuchos) seems completely unprecedented, and the divinity of the winds could only be explained as the persistence of a mythological idea. This is, of course, not impossible, since the author has been shown to have adopted other ‘primitive’ notions as well. Miller (1953) 6–7: ‘The basic question is why these forces or elements of Nature are described as divine. One objection, however, to this interpretation is the fact that this belief in the divinity of winds was frequently connected with magical claims and practices which the author of On the Sacred Disease explicitly rejects as blasphemous in 1. Moreover I am not sure whether the text of Prognostic can bear this interpretation. In the passage in question 56 Hippocratic Corpus and Diocles of Carystus the statement sounds too strange to be accepted as a self-evident idea not needing explanation. Finally, as was already noted by Nestle,31 the restricted interpretation of ‘the divine’ as the climatic factors is absent (and out of the question) in the parallel discussion of the divine character of diseases in chapter 22 of Airs, Waters, Places. Although the writer of Airs, Waters, Places, in accordance with the overall purpose of his treatise, generally assigns to climatic factors a fundamental role in his explanation of health and disease, he does not say anything about their allegedly divine character and surprisingly does not, in his discussion of the divinity of diseases in chapter 22, explain this with an appeal to climatic factors. In the case discussed there (the frequent occurrence of impotence among the Scythians) the prophasies of the disease are purely ‘human’ factors,32 and no influence of climatic factors (gn»nta oÔn crŸ tän paq”wn tän toioÅtwn t‡v fÅsiav, Âkoson Ëp•r tŸn dÅnamin e«sin tän swm†twn, Œma d• kaª e­ ti qe±on ›nesti –n t¦€si noÅsoisin, kaª toÅtwn tŸn pr»noian –kman- q†nein), the distribution of p†qov (or n»shma, which is the varia lectio) and noÓsov suggests that in the author’s opinion the first thing for the physician to do is to identify the nature of the patho- logical situation (which consists in diagnosis and, as the text says, in determining the extent to which the disease exceeds the strength of the patient’s body) and at the same time to see whether ‘something divine’ is present in the disease in question. As the structure of the sentence (the use of the participle gn»nta and of the infinitive –kmanq†nein) indicates, it cannot be maintained (as Kudlien believes) that a distinction is made here between diseases which result in death and diseases of divine, i. Another objection to Kudlien’s view is that the wording e­ ti qe±on ›nesti –n t¦€si noÅsoisin apparently implies that a certain disease may (but need not) contain a divine element, whereas if meteorological or environmental medicine were referred to here, it would only be possible to say that a disease has a climatic cause or that it has not. Besides, we may wonder whether his claim that in different areas the significance of the symptoms remains the same is compatible with the principles of environmental medicine as stated in Airs, Waters, Places. I see no other possibility than to interpret the passage as a recognition (which may be quite perfunctory or just in order to be on the safe side) that in some cases a disease may be sent by a god and that, consequently, in these cases human treatment is useless (so that the physician cannot be blamed for therapeutic failure) and, perhaps (though this is not explicitly stated), that it can only be cured by divine agency; nor do I see why this interpretation would be inconceivable (for a similar case cf. On the Nature of the Woman 1, where the possibility that a divine element is present in diseases is recognised, without this possibility being specified or explained or taken into account in the course of the treatise). Then they try to cure themselves by means of cutting the vein which runs behind each ear. Of course the validity of this argument depends on the assumption of a common author of On the Sacred Disease and Airs, Waters, Places and on the presumption that he has not changed his opinion on the subject – a long-standing issue which is still a matter of disagreement. It is evident that this question would have to be settled on other grounds as well, for possible divergencies in the concepts of the divine expressed in the two treatises might equally well be taken as ground for assuming two different authors. But it can hardly be denied that the first interpretation necessarily presup- poses all of them and that the champions of this interpretation should take account of them. It therefore remains to consider whether the second interpretation (2) rests on less complicated presuppositions. On this interpretation the disease is divine in virtue of having a phusis,a ‘nature’ (in the sense defined above: a regular pattern of origin and growth). This appears to be closer to the text of the three passages quoted: the mention of phusis in 1. This corresponds very well with the use of ‘human’ (ˆnqrÛpinov) in the author’s criticism of the magicians (1. Grensemann (1968c) 7–18 and the interesting analysis by Ducatillon (1977) 197–226; see also van der Eijk (1991). Theios and anthropinos¯ refer to aspects of diseases, but not, as in the first interpretation, in the sense of their being caused by divine factors and human factors (which would after all imply the incompatibility of the two words). Furthermore, on this view On the Sacred Disease and Airs, Waters, Places express the same doctrine concerning the divinity of diseases, and in both treatises the use of theios is justified by the connotations ‘unchanging’, ‘imperishable’ and ‘eternal’. The fact that all diseases have a nature, a definite pattern of origin and growth or cause and effect, constitutes the element of ‘constancy’ which inheres in the word theios. Perhaps also the connotation of ‘oneness’ or ‘definiteness’ is present here, in that all the various and heterogeneous symptoms and expressions of the disease, which the magicians attributed to different gods (1. But in order to understand the divinity of the disease the mention of the divine character of these factors is, strictly speaking, irrelevant, because it suffices for the author to have demonstrated that the disease is caused by natural factors which constitute its phusis. A possible solution to this problem is to adopt the reading of the manuscript (which is in general not less reliable than the other authority 34 As1. It is highly questionable whether the author of On the Sacred Disease can be credited with the identification of the divine with ‘rational’ or ‘knowable’: the only explicit statement which might support this association is his criticism of the idea that what is divine cannot be known or understood (1. Nor does the association of theios with the ‘laws’ of Nature have any textual basis (on the difference between the nature of the disease and Nature in general see below, pp. On the Sacred Disease 59 M),36 which has taÅth€ instead of taÓta, and to take the diseases as the subject of –st©: ‘in this way (or, in this respect) they are divine’ (taÅth€ d’ –stª qe±a).

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A theory is merely a In pathology buy oxybutynin 5 mg online, as in physiology 2.5mg oxybutynin fast delivery, the true worth of an scientific idea controlled by experiment cheap 5 mg oxybutynin. Council has called on his colleagues for quicker Introduction to the Study of Experimental Medicine () identification and treatment for alcoholic doctors discount oxybutynin 2.5 mg with mastercard. Our hospital organization has grown up with no Introduction to the Study of Experimental Medicine () plan discount 5 mg oxybutynin fast delivery, with no system. I would rather be kept alive in Men who have excessive faith in their theories or the efficient if cold altruism of a large hospital than ideas are not only ill prepared for making expire in a gush of warm sympathy in a small one. Introduction to the Study of Experimental Medicine () Attributed to Bevan in Harley Street p. Beveridge – Isaac was old, and his eyes were dim, so that he Professor of veterinary science could not see. Genesis :  People whose minds are not disciplined by training often tend to notice and remember events that Give me children or else I die. Genesis :  The Art of Scientific Investigations Preface Let us eat and drink; for tomorrow we die. Isaiah :  Probably the majority of discoveries in biology and medicine have been come upon unexpectedly, or at We have made a covenant with death. V the anguish, for joy that a man is born into the He is a bold man who submits his paper for world. But Ahijah could not see; for his eyes were set by The Art of Scientific Investigation Ch. Ecclesiasticus :  Matthew :  and Luke :  Be not slow to visit the sick: for that shall make The light of the body is the eye. Matthew :  Ecclesiasticus :  They that be whole need not a physician, but they The Lord hath created medicines out of the earth; that are sick. Matthew :  Ecclesiasticus :  And if the blind lead the blind, both shall fall into Honour a physician with the honour due unto him the ditch. Ecclesiasticus : – Proverbs :  And God said, Let us make man in our image, after The wringing of the nose shall bring forth blood. Genesis :  Man’s days shall be to one hundred and twenty Xavier Bichat – years. French surgeon, Paris Genesis :  Life is the sum of the functions that resist death. But the men of Sodom were wicked and sinners Attributed before the Lord exceedingly. We cannot therefore deny that a change in just Genesis :  one of an organ’s tissues is frequently enough to Ye shall circumcise the flesh of your foreskin; and it disturb the functions in all the others; yet likewise, shall be a token of the covenant betwixt me and you. Genesis :  Attributed    ·   August Bier – The education of the doctor which goes on after German professor of surgery he has his degree, is, after all, the most important part of his education. A smart mother makes often a better diagnosis Boston Medical and Surgical Journal :  () than a poor doctor. Attributed It has been considered from the point of view of Medical scientists are nice people, but you should the hygienist, the physician, the architect, the not let them treat you. Medicine is like a woman who changes with the Public Health Reports :  (–) fashions. Attributed The public is not always sagacious, but in the long run, it does somehow contrive to find out who are In America there exist professional anaesthetists. A weak person who yields to the It is quite correct to distinguish between medical temptation of denying himself a pleasure. A prestidigitator who, putting metal into your mouth, pulls coins out of your pocket. Can there be a better preparatory school for the The Devil’s Dictionary physician than the study of the natural sciences? A place in which the dead are laid to It is a most gratifying sign of the rapid progress of await the coming of the medical student. The physician can do all he has to do with speed Epigrams and precision, but he must never appear to be in a hurry, and never absent-minded. The Medical Sciences in the German Universities When we know that a case is self-limited or incurable, we are to consider how far it is in our Solitary, meditative observation is the first step in power to palliate or diminish sufferings which we the poetry of research, in the formation of are not competent to remove. Biggs – knife when these chances are lacking is to Professor of Medicine, New York prostitute the splendid art of surgery, and to The human body is the only machine for which render it suspect among the laity and among there are no spare parts. Radio Talk (quoted in Doctor’s Legacy) Quoted in The Great Doctors—A Biographical History of Medicine p. Ltd, ) British reformer Statistics are like women; mirrors of purest You cannot legislate a new layer of cortical gray virtue and truth, or like whores to use as one matter into, or a cirrhosed liver out of, a man. Little, learn more in a year than by abstract reasoning in Brown and Company, Boston () an age.

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Which of the following reg- 25/min purchase 5 mg oxybutynin, and oxygen saturation of 92% on 100% face imens constitutes appropriate venous thromboembolism mask buy cheap oxybutynin 2.5 mg. A 68-year-old woman presents to the emergency tions order 5 mg oxybutynin overnight delivery, and the patient recently was told that he has bron- room complaining of dyspnea order oxybutynin 2.5 mg with visa. Chest radiography is likely to show which of gressive shortness of breath over the past 2 weeks 2.5 mg oxybutynin amex. Bihilar lymphadenopathy smokes a pack of cigarettes daily and has done so since B. Water balloon–shaped heart piratory rate 24 breaths/min, and SaO2 94% on room air. A 78-year-old woman is admitted to the medical in- There is dullness to percussion halfway up her right lung tensive care unit with multilobar pneumonia. Breath sounds are presentation to the emergency room, her initial oxygen decreased without egophony. The examination is other- saturation was 60% on room air and only increased to wise normal. She was in marked ing pleural effusion on the right and also suggests respiratory distress and intubated in the emergency mediastinal lymphadenopathy. Which of the following tests is most likely to yield the cause of the pleural effusion? A 36-year-old male comes to his primary care physician complaining of 3 days of worsening head- ache, left frontal facial pain, and yellow nasal discharge. Acts at β1-adrenergic receptors and dopaminergic into your clinic requesting treatment for “the flu. It also causes vasodilatation and increased sweats, headaches, myalgias, and a nonproductive cough. Acts at β1- and, to a lesser extent, β2-adrenergic re- cently finished doing structural repairs on his old house. Acts at α and β1-adrenergic receptors to increase min, and SaO2 is 88% on room air. A 42-year-old male presents with progressive dyspnea ing and obtunded, localizes to pain, and has flat neck veins. He also is complaining of a primarily dry cough, for initial laboratory testing sent off, and electrocardio- although occasionally he coughs up a thick mucoid spu- gram and chest x-ray are obtained. He does not smoke been called to the bedside and is assessing the patient’s air- cigarettes. A 24-year-old woman is brought to the emergency room after attempting suicide with an overdose of heroin. An 86-year-old nursing home resident is brought by On arrival at the emergency department in Jacksonville, ambulance to the local emergency room. She is hypotensive with a blood pressure of had been coughing and complaining of chills for the past 84/60 mmHg and a heart rate of 80 beats/min. The oxy- few days; no further history is available from the nursing gen saturation is 70% on room air. His past medical history is remarkable for Alz- is performed showing the following: pH 7. Which of the following state- gency responders were able to appreciate a faint pulse and ments is true regarding the patient’s arterial blood gas? The patient is hypoxic due to hypoventilation with 88/51 mmHg and heart rate is 131 beats/min. The patient is hypoxic due to hypoventilation with a stable on transfer; however, 20 min after arrival he is normal A – a gradient. The patient is hypoxic due to shunt with an in- tremities are cool, and blood pressure is difficult to ob- creased A – a gradient. The patient is hypoxic due to ventilation-perfusion turns to you and asks what you would like to do next. Which of the following accurately represents the physio- logic characteristics of this patient’s condition? Which of the following statements best describes the functional residual capacity of the lung? The volume of gas at which the tendency of the A lungs to collapse (elastic recoil pressure) and the B tendency of the chest wall to expand are equal. The volume of gas remaining in the lungs at the end D of a normal tidal exhalation E C. Diminished protein C level ited due to her fatigue, and there is significant orthopnea. Diminished protein S level During her evaluation, laboratory analysis reveals: So- E.

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Sara Thorne Native or tissue valves In general discount 2.5mg oxybutynin with amex, regurgitant lesions are w ell tolerated during pregnancy buy 5mg oxybutynin mastercard, w hereas left sided stenotic lesions are not (increased circulating volum e and cardiac output lead to a rise in left atrial pressure) buy 5 mg oxybutynin free shipping. Nitrates m ay be useful trusted 2.5 mg oxybutynin, but should be used w ith caution in those w ith aortic stenosis order oxybutynin 2.5mg overnight delivery. M echanical valves Anticoagulation is the issue here: in particular, the risk of w arfarin em bryopathy vs risk of valve throm bosis. The patient m ust be fully inform ed, and involved in deciding her m ode of anticoagulation (m edicolegal im plications). Failure of adjusted doses of sub- cutaneous doses of heparin to prevent throm boem bolic phenom ena in pregnant patients w ith m echanical cardiac valve prostheses. The key here is to leave the m other off w arfarin for the m inim um tim e possible. An elective section is perform ed at 38 w eeks’ gestation, replacing the w arfarin w ith unfractionated heparin for the m inim um tim e possible • Severe aortic or m itral stenosis. If the m other’s life is at risk, section follow ed by valve replacem ent m ay be necessary. Controversy rem ains over w hether the follow ing patients should undergo elective Caesarean section: 1 Cyanotic congenital heart disease w ith im paired fetal grow th. Section m ay help to avoid further fetal hypoxaem ia, but at the 100 Questions in Cardiology 199 expense of excessive m aternal haem orrhage to w hich cyanotic patients are prone. A balance has to be m ade betw een a spontaneous vaginal delivery w ith the m other in the lateral decubitus position to attenuate haem odynam ic fluctuations, forceps assistance and the sm aller volum e of blood lost during this type of delivery, and the controlled tim ing of an elective section. Probably m ore im portant than the route of delivery is peri-partum planning and team w ork: delivery m ust be planned in advance, and the patient intensively m onitored, kept w ell hydrated and not allow ed to drop her system ic vascular resistance. Consultant obstetric and anaesthetic staff experienced in these conditions should be present, and the cardiologist readily available. Rachael James All anticoagulant options during pregnancy are associated w ith potential risks to the m other and fetus. Any w om an on w arfarin w ho w ishes to becom e pregnant should ideally be seen for pre- pregnancy counselling and should be involved in the anti- coagulation decision as m uch as possible. Potential risks to the fetus need to be balanced against the increased m aternal throm - botic risk during pregnancy. Anticoagulation for m echanical heart valves in pregnancy rem ains an area of som e controversy. The use of w arfarin during pregnancy is associated w ith a low risk of m aternal com plications1 but it readily crosses the placenta and em bryopathy can follow exposure betw een 6–12 w eeks’ gestation, the true incidence of w hich is unknow n. A single study has reported that a m aternal w arfarin dose 5m g is w ithout this em bryopathy risk. Conversion to heparin in the final few w eeks of pregnancy is recom m ended to prevent the delivery of, w hat is in effect, an anticoagulated fetus. Studies have been criticised for the use of inadequate heparin dosing and/or inadequate therapeutic ranges4 although a recent prospective study w hich used heparin in the first trim ester and in the final w eeks of pregnancy reported fatal valve throm boses despite adequate anticoagulation. Use in pregnancy is m ainly for throm boprophylaxis rather 100 Questions in Cardiology 201 than full anticoagulation but experience is increasing. M anagement W om en w ho do not w ish to continue w arfarin throughout preg- nancy can be reassured that conceiving on w arfarin appears safe but conversion to heparin, to avoid the risk of em bryopathy, needs to be carried out by 6 w eeks. Possible regim es include: • W arfarin throughout pregnancy until near term and then conversion to unfractionated heparin. Coum arin anticoagulation during pregnancy in patients w ith m echanical valve prostheses. Guidelines on the prevention, investi- gation and m anagem ent of throm bosis associated w ith pregnancy. Failure of adjusted doses of subcutaneous heparin to prevent throm boem bolic phenom ena in pregnant patients w ith m echanical cardiac valve prostheses. Matthew Streetly M echanical heart valves are associated w ith an annual risk of arterial throm boem bolism of <8%. This constitutes an unacceptable risk for patients undergoing m ajor surgery, and it is necessary to tem porarily institute alternative anticoagulant m easures. If surgery cannot be delayed, the effect of w arfarin can be reversed by fresh frozen plasm a (2–4 units) or a sm all dose of intravenous vitam in K (0. Recom m encing intravenous heparin in the im m ediate post- operative period m ay increase the risk of haem orrhage to greater levels than the risk of throm boem bolism w ith no anticoagulation. Heparin is usually restarted 12–24 hours after surgery, depending on the type of surgery and the cardiac reason for w arfarin. W arfarin should be restarted as soon as the patient is able to tolerate oral m edication.

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