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Reflections on the Lack of Consideration of Ethnic Ancestry to Stratify Clozapine Dosing
Jose de Leon(Jose de Leon ) 대한신경정신의학회 2023 PSYCHIATRY INVESTIGATION Vol.20 No.3
This review article argues against trusting standard clozapine references, including the US package insert, because they do not include advances in the sciences of pharmacokinetics and pharmacovigilance and ignore the effects of ethnic ancestry on therapeutic dosing. The minimum therapeutic dose leading to the minimum therapeutic concentration of 350 ng/mL in serum/plasma can be used to compare individuals/groups with treatment-resistant schizophrenia. The US clozapine package insert recommends targeting doses of 300-450 mg/day and, subsequently, increments of up to 100 mg with a maximum dose of 900 mg/day. Ethnic ancestry is defined by DNA ancestry group. Asians (people with ancestry ranging from Pakistan to Japan) and Indigenous Americans are similar in clozapine dosing; their average clozapine minimum therapeutic dose ranged from 166 mg/day (female non-smokers) to 270 mg/day (male smokers). For those with European ancestry, average clozapine minimum therapeutic doses ranged from 236 mg/day (female non-smokers) to 368 mg/day (male smokers). Based on limited studies, Black (African sub-Saharan ancestry) patients may be treated with typical US doses (300-600 mg/day), assuming no poor metabolism (PM) status. Ancestry’s impact on clozapine lethality in four countries is discussed (two countries with highly homogenous populations, Denmark and Japan, and two countries with increasingly heterogenous populations due to immigration, Australia and the UK). An international guideline with 104 authors from 50 countries/regions was recently published, providing 6 personalized clozapine titration schedules for adult inpatients (3 ancestry groups and PM/non-PM schedules) and recommending c-reactive protein monitoring at baseline and weekly for 4 weeks.
Leon Azefack Tapondjou,Kemvoufo Beaudelaire Ponou,Remy Bertrand Teponno,Marius Mbiantcha,Jules Desire Djoukeng,Telesphore Benoit Nguelefack,Pierre Watcho,Aurelio Gomez Cadenas,박희준 대한약학회 2008 Archives of Pharmacal Research Vol.31 No.5
A new steroidal saponin, mannioside A (1), was isolated from the stem bark of Dracaena mannii, together with the known pennogenin (2), pennogenin-3-O-β-D-glucopyranoside (3) and pennogenin-3-O-α-L-rhamnopyranosyl-(1→2)-[α-L-rhamnopyranosyl-(1→3)]-β-D-glucopyranoside (4). Their structures were determined using 1D- and 2D-NMR spectroscopy and mass spectrometry. Compounds 1 and 3 significantly inhibited carrageenan-induced paw edema in the rat; compound 4 was moderately active whereas 2 showed very weak activity.
Liability in the context of space tourism
Leon, Pablo Mendes De Korea Society of Air Space Law and Policy 2007 한국항공우주정책·법학회지 Vol.2007 No.special
This article is dedicated to my colleague and friend Professor Soon-Kil Hong, Ph.D, who is the famous President of the Korean Association of Air and Space Law and distinguished teacher at the prestigious Hankuk Aviation University. I had the honour and pleasure to teach there a few years ago - upon his gracious invitation. Professor Soon-Kil Hong has made a long, outstanding and impressive career in aviation and space activities, both from a practitioners and academic perspective. That is why I have tried to find a subject which addresses these facets of his personality although this humble article cannot do justice to the great merits of Professor Soon-Kil Hong. This article discusses the liability aspects for damages and injuries to passengers on suborbital flights, by examining: 1. Recent developments regarding space tourism 2. Suborbital flights in relation to the Chicago Convention 3. The application of space law treaties to space tourism 4. Potential candidates for liability regimes applying to space tourism 4.1 Introduction 4.2 Liability under international space law 4.2.1 The Outer Space Treaty (1969) 4.2.2 The Liability Convention (1972) 4.2.3 Conclusions 4.3 Liability under international private air law 4.3.1 Introduction 4.3.2 The Warsaw Convention (1929), as variously amended 4.3.3 The Montreal Agreement (1999) 4.3.4 Conclusions 5. Final observations
Leon-Hernandez, Saul Renan,Padilla, Eleazar Lara,Algara, Alfredo Cortes,Rodriguez, Noemi Cardenas,Sanchez, Esau Floriano,Cruz, Jaime Lopez,Barradas, Cesar Miguel Mejia,Bandala, Cindy Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.14
Background: An association between alcohol/tobacco use and risk of metastasis in breast cancer has been clearly shown. Materials and Methods: The present study explored, in 48 samples of tissue from mammary ductal carcinoma (taken from Mexican women with an average age of $58.2{\pm}10.9$ years), the association of risk of metastasis with the status of hormonal receptors and the c-erbB2 protein (by immunohistochemistry) as well as clinical, histopathological and sociodemographic factors. Results: Of 48 patients, 41.6% (20/48) presented with metastasis, 43.8% were positive for the estrogen receptor (RE+), 31.3% for the progesterone receptor (RP+) and 47.7% for c-erbB2 (c-erbB2+). The following combinations were found: RE+/RP+/c-erbB2+ 8.3%, RE+/RP+ 22.9%, RE+/RP- 20.8%, RE-/RP+ 8.3%, RE-/RP-/c-erbB2- 22.9% and RE-/RP- 47.8%. There were 12 patients who used alcohol/tobacco, of which 91.6% did not present metastasis and 81.9% were RE-/RP-. Compared to the RE-/RP-/c-erbB2+, the RE+/RP+/c-erbB2+ group had a 15-fold greater risk for metastasis (95%CI, 0.9-228.8, p=0.05). The carriers of the double negative hormonal receptors had a 4.7 fold greater probability of being (or having been) smokers or drinkers (95%CI, 1.0-20.4, p = 0.03). Conclusions: There was a clear protective effect of using alcohol and/or tobacco, in the cases included in the present study of mammary ductal carcinoma, associated with double negative hormonal receptors. However, this association could be due to a protective factor not measured (Neyman bias) or to a bias inherent in the rate of hospitalization (Berkson fallacy). This question should be explored in a broad prospective longitudinal study.
Encounters and Dialogues: Styles and Levels of Communication in Philosophical Practice
Leon de Haas 강원대학교 인문과학연구소 2011 Journal of Humanities Therapy Vol.2 No.-
The world of philosophical practice is a patchwork of partly vague, partly not reducible styles and methods. We badly lack a common language regarding the quality of philosophical practice. The author contributes to the professional discussion of philosophical practice by being explicit about his approach. He characterizes his phenomenologically inspired way of philosophical practice as ‘dialogical encounter’. He describes some examples from his coaching practice. In the last part of the essay, he makes a distinction between encountering and procedural practices by describing two events.