Clinical experiments

Metrifonate [52-68-6] (24) is itself not an AChE inhibitor, but is none2ymaticaIly converted into an active irreversible inhibitor of the en2yme. The compound is relatively specific for AChE over butyrylcholinesterase (135) and the irreversible nature of its inhibition gives rise to an extended duration of action. Some clinical experience has been gained through its use to treat schistosomiasis (136,137) and it is undergoing clinical evaluation for AD. 

Introduced in 1898, heroin was heralded as a nonaddictive alternative to morphine. Subsequent clinical experience showed it to be highly addictive and preferred by addicts over morphine (13). Heroin is approximately ten times more potent than morphine, with quicker onset and shorter duration of... 

In 1991 the foUowiag amiaoglycosides were most important ia medical practice. Clinical experience is most extensive for the first four. 

The first clues to the treatment of scurvy occurred in 1535—1536 when Jacques Cartier, on advice from Newfoundland Indians, fed his crew an extract from spmce tree needles to cure an epidemic. Various physicians were recommending the use of citms fmits to cure scurvy in the mid-sixteenth century. Two hundred years later, in 1753, it was proved by Dr. James Lind, in his famous clinical experiment, that scurvy was associated with diet and caused by lack of fresh vegetables. He also demonstrated that oranges and lemons were the most effective cure against this disease. In 1753, inM Treatise on the Scurvy[ Lind pubhshed his results and recommendations (7). Eorty-two years later, in 1795, the British Navy included lemon juice in seamen s diets, resulting in the familiar nickname "limeys" for British seamen. Evidence has shown that even with undefined scorbutic symptoms, vitamin C levels can be low, and can cause marked diminution in resistance to infections and slow healing of wounds. 

Research and clinical experience on dmg resistance suggests that tumor cells are particularly adept at genetic selections leading to alterations in the stmcture, function, or synthesis of proteins involved in the antitumor dmg action and detoxification. Multiple mechanisms of resistance have been shown to account for the resistance seen in the clinic (46). 

Clinical experience has shown that certain types of lens materials are more prone to deposit problems. In general, lenses with negatively charged moieties at the surface accumulate greater amounts of lysozyme, the principal tear film protein (10). The introduction and use of disposable lenses make these deposits and their clinical problems less significant. 

Although a variety of test methods, eg, Dk, modulus, and tear strength, exist to determine key properties of potential contact lens materials, a number of properties, eg, wettabihty and deposition, have no predictive methodology short of actual clinical experience. 

Alloys based on Ag—Pd have been used for a number of years and are available from most gold alloy manufacturers (148). The palladium content is 22—50 wt % silver content is from 35 to 66 wt %. Minor amounts of Zn, In, or Sn are often present to increase fluidity. Both In and Sn form intermetaUic compounds with both Pd and Ag and, therefore, some of the commercial alloys are susceptible to age hardening (149). These alloys are somewhat difficult to fabricate and require meticulous processing. They may also produce a greenish discoloration when they are fused with porcelain veneers. Nevertheless, clinical experience generally has been satisfactory, and cost is the primary criterion for use. 

Incorporation of the phenethyl moiety into a carbocyclic ring was at first sight compatible with amphetamine-like activity. Clinical experience with one of these agents, tranylcypromine (79), revealed the interesting fact that this drug in fact possessed considerable activity as a monamine oxidase inhibitor and as such was useful in the treatment of depression. Decomposition of ethyl diazoacetate in the presence of styrene affords a mixture of cyclopropanes in which the trans isomer predominates. Saponification gives acid 77. Conversion to the acid chloride followed by treatment with sodium azide leads to the isocyanate, 78, via Curtius rearrangement. Saponification of 78 affords tranylcypromine (79). 

Bechtol in reviewing his clinical experience with 1087 cemented Charnley and Bechtol total hip replacements concluded that prosthetic stem failure is actually the final sequence of previous failures of bony and cement support. His suggested sequence of events leading to prosthetic stem failure have been substantiated in the literature and are as follows ... 

Using this preparation, a 500 mg oxalate calculus obtained surgically was almost completely dissolved within 60 hours. When the solution pH was lowered to 6.0, the dissolution efficiency dropped appreciably and 200 mg of the stone remained undissolved after 60 hours. In another experiment a 5 % EDTA solution adjusted to pH 6.0 was applied in vitro to a phosphate kidney calculus (400 mg) which dissolved almost completely in 30 hours. However, clinical experience indicates that EDTA is still far from ideal for dissolving oxalate and phosphate calculi because of the very long time required for dissolution of the calculi. 

Although anti-TNFa agents are well tolerated and have a good overall safety profile, pitfalls to the use of these drugs apparent with increasing clinical experience include infective complications and, in particular, reactivation of tuberculosis. To date, no statistically significant increased rate of tumour occurrence over that expected has been noted although cases of lymphoma have rarely been reported in patients treated with TNFa blockade. 

Hofland LJ, der Hoek J, van Feelders R et al (2005) Pre-clinical and clinical experiences with novel somatostatin ligands advantages, disadvantages and new prospects. J Endocrinol Invest 28(11 Suppl) 36-42... 

It is anticipated that buprenorphine will be an acceptable treatment for younger addicts and for individuals with smaller habits and shorter histories of dependence, thus permitting earlier intervention in the course of the addiction. Clinical experience suggests that buprenorphine is less effective for individuals with larger opioid habits. Methadone or LAAM remains the preferred medication for those patients. 

Tennant FS, Rawson RA, Pumphrey E, et al Clinical experiences with 959 opioid-dependent patients treated with levo-alpha-acetylmethadol (LAAM). J Suhst Abuse Treat 3 195-202, 1986... 

Pharmacodynamic tolerance to the psychomotor effects of benzodiazepines has been demonstrated after single or multiple doses (File 1985 Greenblatt and Shader 1978 Rosenberg and Chiu 1985). Pharmacodynamic tolerance to the anxiolytic effect (over a 6-month period) has not been demonstrated (Rickels et al. 1983), and clinical experience supports the view that many patients with anxiety disorders require long-term therapy with benzodiazepines or alternative antianxiety agents. An important clinical consequence of tolerance to sedative effects is observed in benzodiazepine overdoses, when patients may initially be... 

Clinical experience suggests that alprazolam can be particularly difficult to taper when lower doses are reached (e.g., tapering from 1 to 0 mg) (Ciraulo et al. 1990). One possible explanation for this is suggested by data from an animal model showing that alprazolam at doses of 0.02—0.05 mg/kg increases benzodiazepine receptor number above baseline (Miller et al. 1987). When difficulty is encountered in tapering the last 1—2 mg of alprazolam, the rate of dose reduction can be decreased to 0.25 mg/week, and/or adjunctive medication may... 

Low K, Crestani F, Keist R, et al Molecular and neuronal substrate for the selective attenuation of anxiety. Science 290 131-134, 2000 Luddens H, Pritchett DB, Kohler M, et al Cerebellar GABAA receptor selective for a behavioural alcohol antagonist. Nature 346 648—651, 1990 LupoloverY, Safran AB, Desangles D, etal Evaluation ofvisual function in healthy subjects after administration of Ro 15-1788. Eur J Clin Pharmacol 27 505-507, 1984 Maher JF, Schreiner GE, Westervelt FB Jr Acute glutethimide intoxication 1. clinical experience (twenty-two patients) compared to acute barbiturate intoxication (sixty-three patients). Am J Med 33 70-82, 1962 Marks J The Benzodiazepines Use, Overuse, Misuse, Abuse. Baltimore, MD, University Park Press, 1978... 

Reich DL, Silvay G Ketamine an update on the first twenty-five years of clinical experience. Can J Anaesth 36 186—197, 1989 Ricaurte GA, Forno LS, Wilson MA, et al (+/-)3,4-Methylenedioxymethamphetamine selectively damages central serotonergic neurons in nonhuman primates. JAMA 260 51-55, 1988... 

This chapter is intended to provide an overview of HIV-1 entry inhibitors, focusing on the mechanism of action, development, and knowledge of viral resistance to the currently available entry inhibitors, enfuvirtide and maraviroc. Although reversed relative to their order in the entry process, enfuvirtide is discussed first due to the greater clinical experience with this drug. 

The first documented use of sUicone as biomaterial was silicone mbber tubing as shunts for treatment of hydrocephalus in about 1955. From 1960 to 1990, the biomedical application of sUicone mbber was steadUy grown. One of the most well-known silicone product is the Norplant contraceptive implant. The first clinical experiment with this device was reported in 1966. FDA approved its use in 1990. 

Matsumura G, Hibino N, Ikada Y, Kurosawa H, and Shin oka T. Successful application of tissue engineered vascular autografts Clinical experience. Biomaterials, 2003, 24, 2303-2308. 

Horan RF, Austen KF Systemic mastocytosis retrospective review of a decade s clinical experience at the Brigham and Womens Hospital. J Invest Dermatol 1991 96 5S-13S. 

It is obvious and a well-known clinical experience that psychosomatic influence is extremely common in LA reactions. Figure 2 shows the example of a patient who,... 

The current evidence base for the injection of epinephrine in the initial acute treatment of anaphylaxis includes clinical experience during nearly a century of use, observational studies, epidemiological studies, fatality studies, and randomized controlled trials in people at risk for anaphylaxis although not actually experiencing it at the time of the study. Moreover, the pharmacology of epinephrine has been... 

Ongoing epinephrine research relevant to human anaphylaxis is critically important. In its absence, the use of epinephrine in anaphylaxis treatment in the 21st century will continue to be based mostly on clinical experience, or worse, on expedience, instead of on clinical science. 

The pharmacoeconomics of the anxiety disorders has received litde attention. In the past drug costs were largely incurred by use of benzodiazepines, most of which are available in generic forms and are cheap. They are effective and acceptable in the short term. Long-term use is associated with the risk of physical dependence, with an adverse risk—benefit ratio and high cost terms to facilitate withdrawal. There is now a trend towards the use of antidepressants in the anxiety disorders. Clinical experience has been followed by formal trial evaluation. 

Lovblad KO, Laubach HJ, Baird AE, Curtin F, Schlaug G, Edelman RR, Warach S. Clinical experience with diffusion-weighted MR in patients with acute stroke. Am J Neuroradiol. 1998 19 1061-1066. 

Tanne D, Bates VE, Verro P, Kasner SE, Binder JR, Patel SC, Mansbach HH, Daley S, Schultz LR, Karanjia PN, Scott P, Dayno JM, Vereczkey-Porter K, Benesch C, Book D, Coplin WM, Dulli D, Levine SR. Initial clinical experience with IV tissue plasminogen activator for acute ischemic stroke A multicenter survey. The t-PA Stroke Survey Group. Neurology. 1999 53 424 27. 

Mahon BR, Nesbit GM, Barnwell SL, Clark W, Marotta TR, Weill A, Teal PA, Qureshi Al. North American clinical experience with the EKOS MicroLysUS infusion catheter for the treatment of embolic stroke. Am J Neuroradiol 2003 24 534-538. 

A DA antagonist could certainly counter the increased mesolimbic activity and the positive symptoms. On the other hand, they would not be expected to reduce negative symptoms if these arise through an already inadequate DA influence. This fits with clinical experience because most of the neuroleptics are ineffective in treating negative symptoms. In fact if the negative symptoms do result from loss of the actual cortical neurons, rather than input to them, they will be difficult to reverse and much will depend on the precise role of DA in the DLPFC (see later). 

A link between the central monoamines, 5-hydroxytryptamine (5-HT) and noradrenaline, and depression was forged some 40 years ago and arose from clinical experience with the drugs, reserpine and iproniazid. At that time, reserpine was used as an... 

Both these predictions are borne out by clinical experience despite the snag that only MAOb is found in serotonergic neurons (Saura et al. 1996). So far, there is no explanation for this anomaly. However, the lack of a tyramine-induced pressor effect with moclobemide probably owes more to the fact that it acts as a reversible inhibitor of MAOa (RIMA) than to its isoenzyme selectivity. Its reversible inhibition of MAOa means that, should tyramine ever accumulate in the periphery, it will displace... 

FLEiss J L (1986) The design and analysis of clinical experiments. New York, John Wiley Sons, Inc. 

Clinical experience shows that these cements are durable. For example, a failure rate as low as 2 % has been reported by Mount (1984) in a clinical trial lasting seven years, and Wilson McLean (1988) have cited a number of clinical trials attesting to the durability of this cement. 

In many ways, this situation parallels the clinical experiences, in being... 

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