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Biomedical subjects

Eric Lewin Altschuler

Publications and source records attributed to Eric Lewin Altschuler.

At least 19 recordsLinked to original sources
PubMed2006

Co-administration of ramelton and fluvoxamine to increase levels of interleukin-2.

Ramelton is a medication recently approved by the FDA for treatment of insomnia. Ramelton is an analogue of melatonin with a higher affinity even than that of the natural ligand. Clinically this potentially strong effect of the ligand is blunted by the fact that upon oral ingestion there is first pass metabolism of greater than 95%. This liver metabolism is mediated by the CYP1A2 enzyme. It turns out that the medication fluvoxamine approved by the FDA for the treatment of obsessive compulsive disorder is a potent inhibitor of the CYP1A2 enzyme, with the effect that co-administration of ramelton and fluvoxamine increases blood levels of ramelton by 100-200 fold. It turns out that lymphocytes bear the melatnonin receptors and stimulation of these receptors on lymphocytes cause the lymphocytes to elaborate the pro-inflammatory cytokine interleukin-2 (Il-2). Thus, here we point out that co-administration of ramelton and modest doses of fluvoxamine may be able to smoothly produce increased levels of Il-2, this may be useful in diseases and conditions such as metastatic cancer and maintenance of suppression of the HIV virus.

Adjuvants, Immunologic↗
PubMed2006

Strenuous, intensive, long-term exercise does not prevent or delay the onset of Huntington's disease.

Recent work in mice has suggested that an enriched environment can delay disease onset in models of Huntington's disease (HD). The component of an enriched environment most likely able to be translated to humans is increased exercise. But here I note that a recently reported case of HD in a marathon runner who had, for many years before becoming symptomatic with HD, been running at an advanced amateur/semiprofessional level, suggests that in humans exercise is not able to prevent or even delay onset of HD. In general study of marathon runners may be useful to study if exercise can prevent or delay onset of genetic diseases.

Age of Onset↗
PubMed2006

Situational therapy for Wernicke's aphasia.

Patients with Wernicke's or expressive aphasia are able to produce fluent speech, however, this speech may be complete gibberish sounds and totally incomprehensible, or even when comprehensible to a degree is often laced with severe errors and abnormalities such as verbal and phonemic paraphasias and neologisms. Furthermore, patient's with Wernicke's aphasia have poor to no understanding of speech or language. There is no proven method for rehabilitation of Wernicke's aphasia, or even much guidance for physicians or speech therapists to treat Wernicke's aphasia patients. In contrast to their poor to non-existent communication skills using speech or other forms of language, it has long been appreciated informally and formally that Wernicke's aphasia patients are able to communicate well, even normally, using non-verbal means such as actions, movements, props, gestures, facials expressions, and affect. Furthermore, in non-language domains Wernicke's aphasia patients can show normal memory and learning abilities. Thus, we here suggest that the non-language communication channels of Wernicke's aphasia patients be channeled and utilized in their functional rehabilitation: Specifically, we suggest that therapy for Wernicke's aphasia patients should consist of placing patients in real or simulated important functional situations--e.g., buying food, taking transport--and let the patients train and learn to use and hone their non-language communication means and skills for improved practical functioning.

Aphasia, Wernicke↗
PubMed2006

Defect-free global minima in Thomson's problem of charges on a sphere.

Given unit points charges on the surface of a unit conducting sphere, what configuration of charges minimizes the Coulombic energy SigmaN i>(j=1)1/r(ij)? Due to an exponential rise in good local minima, finding global minima for this problem, or even approaches to do so has proven extremely difficult. For N=10(h2+hk+k2)+2 recent theoretical work based on elasticity theory, and subsequent numerical work has shown, that for N approximately same or greater than 500-1000, adding dislocation defects to a symmetric icosadeltahedral lattice lowers the energy. Here we show that in fact this approach holds for all N, and we give a complete or near complete catalogue of defect free global minima.

Journal Article↗
PubMed2005

Global minimum for Thomson's problem of charges on a sphere.

Using numerical arguments, we find that for N=306 a tetrahedral configuration (T(h)) and for N=542 a dihedral configuration (D5) are likely the global energy minimum for Thomson's problem of minimizing the energy of N unit charges on the surface of a unit conducting sphere. These would be the largest N by far, outside of the icosadeltahedral series, for which a global minimum for Thomson's problem is known. We also note that the current theoretical understanding of Thomson's problem does not rule out a symmetric configuration as the global minima for N=306 and 542. We explicitly find that analogues of the tetrahedral and dihedral configurations for N larger than 306 and 542, respectively, are not global minima, thus helping to confirm the theory of Dodgson and Moore [Phys. Rev. B 55, 3816 (1997)] that as N grows, dislocation defects can lower the lattice strain of symmetric configurations and concomitantly the energy. As well, making explicit previous work by ourselves and others, for N<1000 we give a full accounting of icosadeltahedral configurations which are not global minima and those which appear to be, and discuss how this listing and our results for the tetahedral and dihedral configurations may be used to refine theoretical understanding of Thomson's problem.

Journal Article↗
PubMed2005

Bupropion for fatigue and as a tumor necrosis factor-alpha lowering agent in primary biliary cirrhosis.

Primary biliary cirrhosis (PBC) is a chronic cholestatic disease which can often be severe, progressive and necessitate liver transplantation. The cause of PBC is not known, and treatments other than liver transplantation are often not effective. Among the more common and troublesome symptoms of PBC is fatigue. The etiology of fatigue in PBC is not well-understood, and there is no known treatment for it. Here, we suggest that for a number of reasons that the safe and commonly used oral antidepressant bupropion might be effective for fatigue in PBC: (1) increased monoaminergic and dopaminergic tone to combat fatigue, (2) treatment of concomitant depression, (3) in general for PBC as a tumor necrosis factor-alpha (TNF) lowering agent, if TNF is eventually found to play a role in PBC pathogenesis.

Fatigue↗
PubMed2005

Proposal for using small molecule tumor necrosis factor-alpha lowering agents, possibly bupropion, in aplastic anemia.

Aplastic anemia (AA) is associated with non-trival mortality. Although diagnostic boarders with other myelodysplastic syndromes are unclear, AA is thought, at some point in the chain of events that destroy marrow hematopoiesis, to involve overproduction of tumor necrosis factor-alpha (TNF) and that TNF is the proximal death programming signal the stem cells receive. Thus agents that lower TNF may be of benefit in AA. In preliminary studies we have found that the commonly used antidepressant bupropion lowers TNF. Thus, bupropion is a potential initial small molecule TNF inhibitor to consider for AA.

Anemia, Aplastic↗
PubMed2005

Using histamine (H1) antagonists, in particular atypical antipsychotics, to treat anemia of chronic disease via interleukin-6 suppression.

Anemia of chronic disease (ACD) is a condition of decreased red cell mass secondary to some other chronic inflammatory condition. In ACD total body iron stores are normal, though serum iron is typically low secondary to iron sequestration by macrophages, and often iron supplementation is not an effective treatment for ACD for the same reason. The pathogenesis of ACD had been poorly understood, but recently there has been important progress: upregulation of interleukin-6 (Il-6) secondary to the underlying chronic inflammatory disease upregulates expression of the protein hepcidin. Upregulation of hepcidin causes anemia by a number of mechanisms: decreased intestinal absorption of iron from the duodenum, increased sequestration of iron by macrophages. Thus, downregulation of Il-6 may represent a most important treatment avenue for ACD. Anti-Il-6 antibodies might be a way to lower Il-6 levels, but such antibodies besides being expensive would have to be given intravenously or intramuscularly, and such large immunogenic molecules may not be appropriate in patients already with a chronic inflammatory condition. Here, we note that an immediately available and potentially effective treatment for ACD is to decrease Il-6 levels by histamine (H1) receptor antagonism, given that histamine acting through the H1 receptor is known to be a potent positive regulator of Il-6. Among the classes of medications that are H1 antagonists we point out that atypical antipsychotic medications such as olanzapine and quetiapine are among the most potent H1 antagonists, and can have simple daily dosing schedules and thus may be particularly useful in ACD.

Anemia↗
PubMed2005

The atypical antipsychotic agents ziprasidone [correction of zisprasidone], risperdone and olanzapine as treatment for and prophylaxis against progressive multifocal leukoencephalopathy.

Progressive multifocal leukoencephalopathy (PML) is an unremitting, advancing disease of central nervous system white matter. PML is caused by infection of the JC polyoma virus, most always in patients with immunosupression due to, for example, cancer, anti-rejection transplant medications or HIV. There is no specific treatment or cure for PML, and untreated it has a median life expectancy is less than four months. Highly active antiretroviral treatment (HAART) has greatly reduced the incidence and prevalence of PML in HIV+ patients likely, however, even in the best case scenario of an HIV+ patient with PML and taking HAART, a significant mortality remains. Novel treatments for PML are needed. Recently Atwood and colleagues have found that the cellular receptor for JC virus is the serotonin 5HT2A receptor. In vitro they used the older antipsychotic medications chlorpromazine and clozapine to block the serotonin 5HT2A receptor and block JC virus cell entry. Unfortunately, however, chlorpromazine and clozapine have such significant side effects and toxicities, e.g., extrapyramidal symptoms and the possibility of bone marrow dyscrasias - that they may be problematic to use clinically. Here, we point out that some newer atypical antipsychotics such as zisprasidone, risperidone and olanzapine--medicines with much better side effect and toxicity profiles than the older antipsychotics--in vitro are significantly more potent 5HT2A receptor antagonists than chlorpromazine or clozapine by in some cases more than a factor of 10, and thus may be useful as treatment for or prophylaxis against PML.

Antipsychotic Agents↗
PubMed2005

Interaction of vision and movement via a mirror.

I have noticed a striking effect that vision can have on movement: when a person makes circular motions with both hands, clockwise with the left hand, counterclockwise with the right hand, while watching the reflection of one hand in a parasagitally placed mirror, if one arm makes a vertical excursion, the other arm tends to make the same vertical excursion, but not typically if the excursing arm is viewed in plain vision. This observation may help in understanding how visual feedback via a mirror may be beneficial for rehabilitation of some patients with movement deficits secondary to certain neurologic conditions, and illustrates that the traditional division of neural processes into sensory input and motor output is somewhat arbitrary.

Feedback, Psychological↗