Keck studies

Sml2 can reduce N-0 bonds in many other substrates. In 1995, Keck studied the reduction of the N-0 bond in amide 53. Whereas reducing systems including Al(Hg), Na(Hg) and hydrogenolysis proved unsuccessful, treatment of 53 with Sml2 resulted in smooth N-0 bond reduction to give 54 in 91 % yield (Scheme 4.39).42... 

The total costs are likely to reflect the efficacy of treatment. In one industry-sponsored study (Keck et al, 1996b) treatment with lithium or valproate was compared in relation to classical, mixed and rapid-cycling disorder. Treatment with lithium was associated with lower costs than treatment with valproate for classical bipolar disorder, but treatment with valproate was associated with lower costs than treatment with lithium for mixed and rapid-cycling disorders. This is in keeping with the evidence that valproate is more effective than lithium for certain patients with rapid-cycling disorder and probably also for certain patients with mixed affective states. However, these associations are a guide to predicting response to treatment but are not very specific. 

The evidence base for clinical decisions based on cost-effectiveness for the affective disorders is less clear than for schizophrenia. In bipolar disorder the primary effectiveness of the mainstay treatments, lithium and anticonvulsant pharmacotherapy, is undergoing considerable revision (Bowden et al, 2000). Until this is clarified, cost-effectiveness studies are probably premature. Nevertheless the cost burden in bipolar disorder is qualitatively similar to that in schizophrenia, with in-patient costs being the primary burden and associated social costs in treated patients. The drug costs are even less than those for schizophrenia. In Chapter 5 John Cookson suggests there is little economic evidence to drive prescribing decisions. The in-patient burden does not seem to have altered with the introduction of lithium. The only drug-related study (Keck et al, 1996) showed an obvious difference in treatment costs only when lithium was compared with sodium valproate. Since these are both cheap drugs this is unlikely to influence clinical decisions. The main question is what impact... 

My approach to this issue has been to use the molecular bands of CH, CN and now NH to study the star-to-star abundance variations of C and of N. Since these bands are strong enough to be observed at moderate resolution, I can use the multiplexing capability of the Low Resolution Imaging Spectrograph at Keck (Oke et al 1995) to build up large samples. This effort is being undertaken jointly with Michael Briley of the University of Wisconsin at Oshkosh and with Peter Stetson of the National Research Council, Victoria, Canada. 

S. Keck, T. Peters, Identification of protein containing paint media by quantitative amino acid analysis, Studies in Conservation, 14, 75 82 (1969). 

Spanggord RJ, Gibson BW, Keck RG, et al. 1982a. Effluent analysis of wastewater generated in the manufacture of 2,4,6-trinitrotoluene Characterization study. Environmental Science and Technology 16 229-232. 

Acknowledgments These studies were supported primarily by the Nanoscale Science and Engineering Initiative of the National Science Foundation under NSF Award Number EEC-0647560. This work made use of the J.B. Cohen X-ray Diffraction facility and the Electron Probe Instrumentation Center (EPIC) and Keck Interdisciplinary Surface Science (Keck-II) facility of NUANCE center at Northwestern University. 

Muller MB, Keck ME (2002) Genetically engineered mice for studies of stress-related clinical conditions. J Psychiatr Res 36 53-76... 

Challenge studies in anxiety disorders are highlighted by M.E. Keck and A. Strohle. The heterogeneity of agents capable of producing panic attacks... 

A thorough discussion of this topic is beyond the scope of this chapter. However, a recent review of controlled studies of mood stabilizers (Keck et al, 2000) provides a reasonable summary. Pooling response data from five studies (from 1954 to 1994) and 124 acute manic patients revealed that 70% of the patients had at least partial improvement with lithium treatment. Response took 2-3 weeks, was superior to antipsychotics in ameliorating affective symptoms, produced an improvement in psychosis, but was less effective in treating psychomotor agitation. DSM-III and earlier criteria were used to diagnose the patients in these trials, so these samples may not be comparable to patients in more modern studies. Table 37.2 summarizes a compilation of clinical... 

Systematic studies of combinations of mood stabilizers and atypical antipsychotics, or of benzodiazepines and mood stabilizers, were not included in Keck et al. (2000) review. 

Valproate, a simple branched-chain fatty acid, was first reported as a successful treatment for acute mania by Lambert and colleagues in 1966. Following this report, at least 16 uncontrolled trials consistently supported the observation that valproate has acute and long-term mood-stabilizing effects in patients with bipolar disorder (reviewed by Keck et al. 1992a). Recently, five double-blind controlled studies of valproate have been completed that provide definitive evidence of its efficacy in acute mania. 

To our knowledge, there have been no reports of controlled clinical trials of valproate as a prophylactic agent in bipolar disorder. Results from a number of open trials suggest that perhaps half of patients treated with valproate experience prophylactic benefit (reviewed in Keck et al. 1992a]. A placebo-controlled, double-blind study of the efficacy of the divalproex form of valproate is under way and may provide additional information regarding the use of this drug in the maintenance therapy of bipolar disorder. 

Other factors associated with poor lithium response in mania include a history of prior lithium failure and a diagnosis of schizoaffective disorder. Bowden et al. [1994b] observed in a double-blind, placebo-controlled trial of patients with acute mania that those with a history of lithium response improved on lithium in this trial, whereas those with a history of prior lithium failure did not. Patients with a diagnosis of schizoaffective disorder may respond less well to lithium than patients with bipolar disorder, although this has not been extensively studied [Keck et al. 1994, for review]. 

Calabrese JR, Bowden CL, Sachs GS, et al A placebo-controlled 18-month trial of lamotrigine and lithium maintenance treatment in recently depressed patients with bipolar I disorder. Lamictal 605 Study Group. J Clin Psychiatry 64 1013-1024, 2003 Calabrese JR, Keck PE, Macfadden W, et al A randomized, double-blind, placebo-controlled trial of quetiapine in the treatment of bipolar 1 or 11 depression. Am J Psychiatry 162 1351-1360, 2005 Chen G, Manji HK, Hawver DB, et al Chronic sodium valproate selectively decreases protein kinase C alpha and epsilon in vitro. J Neurochem 63 2361-2364, 1994... 

Some 20 years later, Keck et al. (1989) noted that the course of action of neuroleptics, particularly the onset of their specific antipsychotic action, has still not been studied accurately enough. According to these authors there have been hardly any controlled studies in which clear distinction was made between the non-specific calming action and the antipsychotic effects of neuroleptics. 

Results of crossover studies indicate that lithium is efficacious in treating acute depression in bipolar subjects unequivocally (36%, 29/80) and partially (43%. 34/80). respectively (Xomberg and Pope, 1993 Keck and McElroy, 2002). Various antidepressants have shown variable rates of efficacy in the treatment of acute bipolar depression, i.e. desipramine (50%), maprotiline (67%), imipra-mine (40 60%), tranylcypromine (87%), moclobemide (53%) and fluoxetine (60%) (Keck and McElroy, 2002). Among the anticonvulsants, valproic add and lamotrigine appear to have some potential efficacy in the treatment of acute bipolar depression (Calabrese et al., 1992, 1999 Fatemi et al., 1997). 

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