By L. Jesper. University of Baltimore.
In the Isler-Lindlar method 60pills abana free shipping, excess menadiol monobenzoate is condensed with iso- phytol in the presence of boron trifluoride etherate as a catalyst generic 60 pills abana otc. The trans-enriched alkylation product (trans:cis 9:1) is saponified with potassium hydroxide and oxidized to phylloquinone with oxygen (Weber & Rüttimann order 60 pills abana fast delivery, 1996). The industrial synthesis of menaquinones parallels that of phylloquinone and involves as a key step alkylation of monosubstituted menadione with an appropriate (all-trans) polyisoprenyl derivative. Menaquinones of varying chain lengths, from C5 to C65, have been produced and isolated from bacteria. Menadione can be prepared by oxidizing 2-methylnaphthalene with chromic acid or hydrogen peroxide (Weber & Rüttimann, 1996). A process based on biotechno- logical techniques has been reported in Japan (Van Arnum, 1998). Menadione sodium bisulfite can be prepared by reacting menadione with sodium bisulfite. The compound readily regenerates menadione on treatment with mild alkali and behaves as a typical ketone–sodium bisulfite addition compound (Gennaro, 1985; Van Arnum, 1998). Menadiol sodium phosphate can be prepared by reducing menadione to the diol, followed by double esterification with hydriodic acid, metathesis of the resulting 1,4- diiodo compound with silver phosphate and neutralization of the bis(dihydrogen phosphate) ester with sodium hydroxide (Gennaro, 1995). The modification is catalysed by a micro- somal enzyme called γ-glutamyl or vitamin K-dependent carboxylase, which is present in most tissues. The best-known vitamin K-dependent proteins are those synthesized in the liver, which play a role in the maintenance of normal haemostasis. Vitamin K-dependent proteins, of uncertain function, are also known to occur in a variety of other tissues such as bone, kidney, pancreas, placenta, spleen and lungs. They include the bone protein osteocalcin (also called bone Gla protein) and matrix Gla protein; there is growing evidence that these proteins may be important for bone health and other regulatory functions in calcium metabolism. Naturally occurring phylloquinone and menaquinones all γ-carboxylate the vitamin K-dependent coagulation proteins. Synthetic forms of menadione (and related water-soluble salts) that lack a side-chain at the 3-position have biological activity in vivo only after side-chain alkylation, which results in the specific synthesis of menaquinone-4 (Suttie, 1991; see also section 4). Neonates are born with very limited vitamin K stores, but most infants do not show relevant hypoprothrombinaemia at birth (von Kries et al. Biochemical signs of vitamin K deficiency are common during the first week of life, however, unless sufficient amounts of vitamin K are ingested. The natural diet of newborns is human milk, which contains vitamin K at concentrations of 0. This condi- tion was originally called ‘classical haemorrhagic disease of the newborn’; the present nomenclature is ‘classical vitamin K deficiency bleeding’ (Sutor et al. During the first three months of life, exclusively breast-fed infants remain at risk for vitamin K deficiency bleeding. In many of these infants, the bleeding episode, which is often intracranial haemorrhage, is the first perceived symptom of an under- lying cholestatic disease. In 10–30% of the cases, however, no underlying disease can be found (von Kries et al. After the first three months of life, vitamin K deficiency is almost completely confined to patients with cholestatic diseases (congenital or acquired obstruction of the bile duct), malabsorption syndromes or cystic fibrosis (Houwen et al. The predominant patterns were to give either selective intramuscular prophylaxis only to infants presumed to be at special risk for bleeding (mainly premature and low-birth-weight Table 1. In the early 1950s, water-soluble menadiol sodium phosphate was widely used, until haemolysis due to high doses of this preparation in neonates was identified (Meyer & Angus, 1956). In most countries, phylloquinone has been used since that time, although in some third-world countries water-soluble menadione sodium bisulfite still seems to be used (Sharma et al. Because it is technically difficult to dissolve phylloquinone, only a limited number of preparations became available. The Roche preparation (Konakion®) in which Cremo- phor (polyethoxylated castor oil) is used as an emulsifying vehicle has been widely available in Europe and North America. In Japan, an oral preparation of menaquinone-4 is used instead of phylloquinone (Hanawa, 1992). Almost all cases of vitamin K deficiency bleeding can be prevented by intramuscular administration of 1 mg of vitamin K at birth (von Kries & Hanawa, 1993). Clinical obser- vations and laboratory investigations have also clearly shown that a single oral dose of vitamin K protects against classical vitamin K deficiency bleeding (Clark & James, 1995) but is less effective for prevention of this condition later in life (Tönz & Schubiger, 1988; Ekelund, 1991). Without vitamin K prophylaxis, the incidence of late vitamin K deficiency bleeding in Europe was estimated to be 40–100 per million livebirths, whereas in Asia the condition appears to be considerably more common (Hanawa, 1992; Choo et al. Since intramuscular vitamin K prophylaxis has proven effective against late defi- ciency bleeding, 1 mg of vitamin K at birth was recommended in most western countries (von Kries, 1991). After reports of a potential association between vitamin K prophylaxis and the risk for childhood cancer (Golding et al. In most cases, however, vitamin K deficiency is detectable only by measuring the plasma concentrations of vitamin K or with sensitive biochemical markers of vitamin K deficiency (Cornelissen et al. Additional risk factors, such as therapy with antibiotics that interfere with vitamin K metabolism, may cause bleeding in patients with cystic fibrosis (Nowak et al. Some patients with this disease are given vitamin K supplements, although there are no uniform recom- mendations (Durie, 1994). Mothers on antiepileptic drugs, for example, are at high risk of delivering an infant with manifest vitamin K deficiency (Cornelissen et al. Hypoprothrombinaemia may be caused by some cephalosporins, especially those containing an N-methylthiotetrazole side-chain, and may require vitamin K supple- mentation (Breen & St Peter, 1997).
Adverse reactions • Common: ataxia order 60pills abana with amex, nystagmus buy abana 60 pills visa, diplopia discount 60pills abana mastercard, slurred speech, hypo- tension, nausea, gingival hyperplasia, rashes. Clinically important drug interactions • Drugs that increase effects/toxicity of phenytoin: acute alcohol, isoniazid, chloramphenicol, benzodiazepines, succinamides, amio- darone, estrogens, cimetidine, halothane, methylphenidate, phenothiazines, salicylates, succinamides, sulfonamides, tolbutamide, trazodone, disulfiram. Advise patient to practice good oral hygiene, including gum massage, and make regular dental visits. It is also used for ventricular arrhythmia from digoxin toxicity and following pediatric cardiac surgery. Physostigmine Brand names: Eserine (physostigmine sulfate), Antilirium (phy- sostigmine salicylate). Mechanism of action: Inhibits acetylcholinesterase thereby increasing acetylcholine at cholinergic receptor sites. Onset of Action Peak Effect Duration ophthalmic 20–30 min 2–6 h 12–36 h Food: Not applicable. Contraindications • Parenteral administration: hypersensitivity to physostigmine, peritonitis, mechanical obstruction of intestinal or urinary tract. Editorial comments • Use ophthalmic preparation with caution in patients with angle-closure glaucoma, patients with narrow angles. Advice to patient • Carry identification card at all times describing disease, treat- ment regimen, name, address, and telephone number of treating physician. Clincially important drug interactions • Drugs that increase the requirement for phytonadione: quini- dine, quinine, high-dose salicylates, sulfonamides, antibiotics. Editorial comments • Because phytonadione has a slow onset of action, it may be necessary to administer whole blood or plasma if there is an emergency need due to severe bleeding. Mechanism of action: Competitive blocker of β-adrenergic receptors in heart and blood vessels. Editorial comments • Note that this drug is pregnancy category B; most β blockers are category C. Susceptible organisms in vivo: Staphylococci, Staphylococcus aureus, Streptococcus pneumoniae, beta-hemolytic streptococci, Escherichia coli, Hemophilus influenzae, Klebsiella sp, Neisseria gonorrhoeae, Proteus mirabilis, Enterobacter sp, Pseudomonas aeruginosa, Serratia sp, Clostridium sp (Bacteriodes sp generally are resistant). Editorial comments • Piperacillin is generally used for noscomial pneumonia, sep- ticemia, endocarditis, and soft tissue infections due to susceptible organisms, especially aerobic gram-negative bacteria or Entero- coccus faecalis. Unfortunately, extended-spectrum β-lactamases are produced by more and more aerobic gram-negative bacteria found in noscomial infections. Mechanism of action: Inhibits cyclooxygenase, resulting in inhi- bition of synthesis of prostaglandins and other inflammatory mediators. Warnings/precautions • Use with caution in patients with cardiac or renal disease, dys- phagia, esophageal compression from left atrial enlargement. Such patients should be prescribed potassium prepa- rations that can be dissolved in liquid or are in liquid form. Advice to patient • Do not use potassium-containing salt substitutes without con- sulting treating physician. Such foods include the following: citrus juices, apricots, bananas, raisins, nuts. It may be necessary to have a dietitian work with the patient to ensure the proper dietary regimen. For patients not on digitalis, administer calcium glu- conate or other calcium salt: infuse 0. Hypomagnesemia should be cor- rected prior to administration of potassium for replacement purpose. Editorial comments • Oral replacement therapy for hypokalemia is preferable to parenteral. If acidosis is present, the following salts of potassium should be used: bicar- bonate, acetate, gluconate, citrate. Advice to patient: Use two forms of birth control including hor- monal and barrier methods. Mechanism of action: Pralidoxime reactivates organophosphate inhibited cholinesterase. Adjustment of dosage • Kidney disease: Reduce dose because of decreased creatinine clearance. Contraindications: Hypersensitivity to praldoxime (relative con- traindication), poisoning with inorganic phosphates, phosphorus, organic phosphates that are not cholinesterase inhibitors. Warnings/precautions: May precipitate myasthenic crises when used for treatment of overdose of antimyasthenic drugs (neostig- mine, ambenonium, pyridostigmine). Adverse reactions • Common: pain at injection site, visual disturbances, nausea, dizziness, hypertension, tachycardia, muscle weakness. Clinically important drug interactions: Drugs that increase effects/toxicity of pralidoxime: morphine, theophyline, succinyl- choline, reserpine, phenothiazines, skeletal muscle relaxants, bar- biturates. Editorial comments • When pralidoxime is administered for a suspected organophos- phate poisoning, the following principles should be observed: 1. Some degree of anticholinergic action by atropine should be maintained for at least 48 hours. It may be necessary to administer additional doses of pral- idoxime q3–8h for several days. Patients should be observed for 1–3 days after poisoning episode for recurrence of symptoms.
The theory of conflict generic 60pills abana mastercard, following the psychoanalytic lead order abana 60 pills without a prescription, would presume that a specially large physiologic disturbance would occur when two incompatible reaction tendencies are aroused at the same time order abana 60 pills mastercard. Whether there is a greater disturbance than the sum of the two separate excitations is questionable (3), but at any rate the two would be greater than one. Long habit would dispose the person to answer a critical question straightforwardly. On the other hand, when he is lying there are circumstances which arouse in him the tendency to denial. In the Indiana studies one experiment was based explicitly on this principle, but with the plan of distinguishing the two response tendencies by different sorts of muscular activity. The experiment gave good results, but not because it was possible to distinguish the two reaction tendencies. A better plan might have been to associate a "yes" answer with one hand and a "no" answer with the other. The purpose may be served, however, if the two response tendencies merely summate in the same place, and this could well be the mechanism by which the usual detection test works. On the conflict hypothesis, both reaction tendencies would probably need to be strong for good results. This suggestion again leads to a paradoxical recommendation: the situation must be so ordered that S makes a strong effort to conceal the infor- -162- mation. This strategy, opposite to that which might encourage admissions, may in fact be favorable to instrumental detection. The experiment, already described, which showed better detection when S was encouraged to think he might "beat the instrument" lends itself to this interpretation. If conflict is the basis of the large reactions that signify deception, then there is some danger of confusion with large reactions produced by strictly personal emotional problems. It is an established fact (see the preceding) that words touching on emotionally sensitized areas will produce large reactions, regardless of deception. A question touching on such an area might provoke a reaction greater than that produced by a mild conflict. A third possible basis of detection is the punishment, or better, threat-of-punishment principle. According to this idea a person will give a large physiologic response during lying because he anticipates serious consequences if he fails to deceive. In common language it might be that he fails to deceive the machine operator for the very reason that he fears he will fail. The physiologic reaction would be the consequence of an avoidance reaction which has a low probability of reinforcement, but not too low. If the theory has any validity at all it must be supposed that the physiologic reaction is associated with a state of uncertainty. It does seem that a lie told with a complete certainty of its acceptance would be unlikely to produce much reaction; and on the other hand we have the experimental evidence already mentioned that a lie told with no prospect of success whatever is also poorly detected. For good detection a situation may be necessary where S is willing to gamble on a rather long chance with some hope of success. To make this punishment theory cover the experimental results one needs to take "punishment" in a broad sense, since in experiments S quite often suffers no serious loss if he is detected. He does, nevertheless, lose the game which he is playing and possibly this is -163- countable as a punishment. Once again there seems to be all opposition between procedures designed to secure information and those that would lead to the best instrumental detection. Present knowledge is not sufficient to lead to a decision on which, if any, of these three theories is correct. Since the theories here discussed are not mutually contradictory, it is quite possible that all the conditions referred to are actually operative in some degree in the detection situation. In that event detection would be best when critical questions are associated with somewhat traumatic past events, when S is threatened with possible but not certain punishment as a result of lying, and when critical questions, perhaps by reason of the uncertain consequences, arouse conflicting reactions in S. Although direct, practical experience is lacking, some general findings of laboratory experiments are applicable. The relevance of many of the experiments for the criminal detection problem suffers from the fact that they involved no "crime. From their success, we may conclude that crime is not essential for lie detection. Studies directed specifically to these distinctive problems would be required for more reliable conclusions regarding the applicability of findings from previous experimentation to practical employments in intelligence interrogations. One may suppose that the person questioned, typically, will have little personal involvement in information sought. The questions frequently will not be about something he has done or for which he feels responsible or guilty. Perhaps he is not very deeply motivated to conceal the specific items or information, but loyalties and threatened penalties may dispose him -164- to do so. If the source regards the matter as unimportant, the motivational aspects of the situation would be rather like those in the common demonstration of detecting which card has been picked from a deck, a trick not difficult to do as a parlor game when a "lie detector" is available. However, if the source is highly motivated toward concealment and anticipates reprisals if he "breaks," the situation is rather like crime detection. Special considerations also arise in the intelligence interrogation situation because of the kinds of people to be interrogated, their physiologic condition, their emotional state, and their attitudes. They differ from both the suspected criminals and the normal individuals or college students used in most experiments. The effect of factors like these is scarcely known for the groups already studied. One naturally speculates about the possibility of devising a few recording instruments that would need no attachment to S and might be concealed from him.
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