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Biomedical subjects

S Marder

Publications and source records attributed to S Marder.

11 recordsLinked to original sources

Psychopharmacologic treatment strategies for depression, bipolar disorder, and schizophrenia.

Patients with serious psychiatric disorders are frequently treated by primary care physicians, who may have difficulty keeping up with recent advances in psychiatry. This paper presents an updated synopsis for three major psychiatric illnesses: major depression, bipolar disorder, and schizophrenia. Current definitions, updated diagnostic criteria, short- and long-term treatment strategies with algorithms, and special challenges for the clinician are discussed for each of these illnesses. On the basis of each illness's distinct characteristics, five treatment principles are emphasized: 1) Treatment strategies should be long-term and should emphasize adherence, 2) treatment choice should be empirical, 3) combinations of medications may be helpful, 4) a combination of psychosocial and pharmacologic treatments may be more useful than either alone, and 5) the family or "significant others" as well as a consumer organization need to be involved. Some of the new directions in dinical research to refine these strategies and meet these challenges are also described.

Algorithms↗

Decoding "drug imprints" at the millennium: a proposal to increase accuracy and reduce costs.

The State of Washington mandated the use of imprints on all prescription drugs in 1980 and for "OTC's" in 1991. The FDA implemented federal requirements in 1995. Unfortunately, the FDA permitted the continued use of symbols, logotypes, and trademarks as code components, limiting the use of automated recognition systems. Analyses of several week-long samples of phone inquiries documented imprinting calls, the staff's ability to respond with an identification, the information sources used, and apparent reasons for any failure. In the first week we received 666 decoding requests, which when projected for the year amounted to > 25,000 calls. A review of 1999 data exceeded that number. Staff was able to reach drug identification in 93.8% of inquiries. Uninterpretable symbols and absence of code listings contributed to the 36 failures. Projecting over the US suggested as many as 1.25 million calls costing poison centers $25 million/y. A touch-tone telephone or website response system could permit automated responses. Neither solution is feasible without the elimination of symbols or logotypes when using an exclusively alpha-numeric code.

Drug Labeling↗

Conclusions and treatment recommendations for the acute episode in schizophrenia.

Interventions which reduce symptoms, vulnerability and stress on the one hand and improve psychosocial competence and quality of life on the other are essential components of a comprehensive treatment program in schizophrenia. Drug treatment of acute exacerbations which is adequate with respect to drug type, dose and treatment duration and takes risk/benefit measures into account is at the heart of these interventions and should be applied as early as possible. Subsequent neuroleptic treatment to prevent a relapse should be administered in accordance with established treatment guidelines. Drug treatment must be combined with psychosocial interventions, which should be properly adapted to the particular phase and stage of the illness. Implementation and coordination of various interventions require cooperation between therapists, institutions, the patient and the patient's family.

Acute Disease↗

Formyl peptide-induced chemotaxis of human polymorphonuclear leukocytes does not require either marked changes in cytosolic calcium or specific granule discharge. Role of formyl peptide receptor reexpression (or recycling).

We examined the role of intracellular and extracellular calcium on the ability of human polymorphonuclear leukocytes to migrate chemotactically and reexpress (or recycle) formyl peptide receptors when challenged with the synthetic chemotactic peptide, N-formyl-methionyl-leucyl-phenylalanine (FMLP). Extracellular calcium was not required for either optimal chemotactic responses or receptor reexpression. Depletion and chelation of intracellular calcium resulted in significant diminution in the ability of polymorphonuclear leukocytes to release the specific granule constituents lactoferrin and vitamin B12-binding protein during the process of chemotaxis, but had no effect on the capability of these cells to respond chemotactically. Similarly, chelation of intracellular calcium did not affect the ability of these cells to reexpress a population of formyl peptide receptors. Inhibition of receptor reexpression, by a nonagglutinating derivative of wheat-germ agglutinin, was associated with inhibition of chemotactic responses to FMLP. Thus, it appears that large changes in cytosolic free calcium are not necessary for formyl peptide-induced polymorphonuclear leukocyte chemotaxis. In contrast, continuous reexpression (or recycling) of formyl peptide receptors is required for polymorphonuclear leukocyte chemotactic responses to FMLP, a process that appears to be independent from specific granule fusion with plasma membrane.

Adult↗

Anticholinergic effects on memory: benztropine versus amantadine.

To evaluate anticholinergic effects on cognition and other functions, we studied 60 healthy volunteers in a double-blind crossover trial of two antiparkinsonian agents, benztropine and amantadine. Benztropine 4 mg/day, but not amantadine 200 mg/day, impaired free recall and perception of time, and subjects' perception of their own memory impairment was significantly greater with benztropine. Side effects in general were worse with benztropine, particularly such anticholinergic effects as dry mouth and blurred vision, and benztropine decreased measured salivary flow to a significantly greater degree than amantadine. Our findings support the hypothesis that drugs that decrease cholinergic transmission impair storage of new information into long-term memory, but have little effect on retrieval from memory or on tasks involving only immediate memory. Clinically, anticholinergic agents can levy a considerable burden on memory and time perception.

Adolescent↗

Human neutrophils contain subpopulations of specific granules exhibiting different sensitivities to changes in cytosolic free calcium.

We examined the role of mobilization of intracellular calcium in the ability of human neutrophils to discharge specific granule constituents upon stimulation with the synthetic chemotactic factor, N-formyl-met-leu-phe. Extracellular calcium was not required for optimal secretion of the specific granule markers lactoferrin and vitamin B12-binding protein. Depletion and chelation of intracellular calcium, as well as reconstitution experiments, however, revealed different calcium requirements for stimulated secretion of these markers. N-formyl-met-leu-phe-induced secretion of vitamin B12-binding protein required half-maximal change in intracellular calcium of greater than 20 nM, while lactoferrin requirements were approximately 140 nM. Thus, it appears that cytosolic free calcium modulates fusion of subpopulations of specific granules which with the neutrophil plasma membrane.

Benzofurans↗

Meclofenamate sodium monohydrate inhibits chemotactic factor-induced human polymorphonuclear leukocyte function. A possible explanation for its antiinflammatory effect.

Meclofenamate sodium monohydrate (MSM), a potent nonsteroidal antiinflammatory agent, specifically inhibits chemotactic factor-induced human polymorphonuclear leukocyte functions: chemotaxis, degranulation, and generation of superoxide anion radicals. These effects of MSM were found to be dependent upon the concentrations of drug not bound to albumin (free drug), and were caused by its ability to interfere at both a receptor and post-receptor (i.e., a step distal to mobilization of polymorphonuclear leukocyte intracellular Ca2+) level. These unique actions of MSM may provide a partial explanation for its potent antiinflammatory effect.

Adult↗

The efficacy of piquindone, a new atypical neuroleptic, in the treatment of the positive and negative symptoms of schizophrenia.

Piquindone (RO22-1319), a new "atypical" neuroleptic, was administered for 2 weeks to 37 schizophrenic patients, and the effects of treatment were examined in a double-blind, placebo-controlled trial. "Atypical" neuroleptics are those that block animal behaviors that model antipsychotic actions in humans at doses lower than those necessary to block animal behaviors that model extrapyramidal actions. Our results demonstrate that piquindone led to moderate but significant improvements in the positive symptoms of schizophrenia and to improvements in negative symptoms just below the level of statistical significance. This supports the notion that neuroleptics categorized as "atypical" in preclinical experiments may prove to be clinically efficacious in humans. In addition, our anecdotal observations were that piquindone caused minimal extrapyramidal symptoms. This is consistent with the preclinical data and suggests that atypical neuroleptics may be associated with fewer extrapyramidal side effects in humans than conventional neuroleptics. However, this must be substantiated by further research.

Adult↗