Effects of genetic defects in the CYP2C19 gene on the N-demethylation of imipramine, and clinical outcome of imipramine therapy

Abstract  The relationship between the genetic polymorphism of S-mephenytoin 4'-hydroxylation catalyzed by CYP2C19 and the N-demethylation of imipramine was examined in 10 Japanese depressed patients. Five patients, who were poor metabolizers of S-mephenytoin, were determined to be either homozygous for a mutation in exon 5 or heterozygous for mutations in exon 4 and exon 5 of the CYP2C19 gene. In contrast, five patients, who were extensive metabolizers, had no mutations. The demethylation index (the desipramine/imipramine ratio) was significantly lower in patients with genetic defects. Plasma levels of imipramine and 2-hydroxyimipramine normalized by the daily dose (mg) per weight (kg) were significantly higher in patients with genetic defects. This suggests that the N-demethylation of imipramine is impaired in patients with genetic defects in the CYP2C19 gene, and that genotype determination may be useful in preventing side effects induced by unexpectedly elevated levels of imipramine.     

Susceptibility genes for schizophrenia

Abstract  It is well known that genetic factors contribute to the susceptibility for schizophrenia. Recent advances in the molecular genetics of schizophrenia strongly suggest several susceptibility genes (e.g. dysbindin, neuregulin-1, DISC1, COMT, G72, RGS4 and Akt1). We discuss the evidence and biology of these genes. As glutamate transmission is especially implicated in these genes, neurobiological basis of schizophrenia might be elucidated by investigation of functional interactions between susceptibility genes for schizophrenia and the glutamatergic system.     

Risk factors for COVID-19-related death,hospitalization and intensive care: a population-wide study of all inhabitants in Stockholm

European Journal of Epidemiology - Since the beginning of the Covid-19 pandemic, the scientific community has explored determinants of Covid 19 disease severity. However, the majority of studies...     

Facing inadequacy and being good enough: psychiatric care providers' narratives about experiencing and coping with troubled conscience

The aim of this study is to illuminate the meaning of encounters with a troubled conscience among psychiatric therapists. Psychiatric care involves ethical dilemmas which may affect conscience. Conscience relates to keeping or losing a sense of personal integrity when making judgments about one's actions. Ten psychiatric therapists were interviewed in June 2006. The interviews were tape-recorded, transcribed verbatim and interpreted using a phenomenological-hermeneutic method. Two themes Facing inadequacy and Struggling to view oneself as being 'good enough' are presented. In the therapists interviewed, awareness of their use of power, a sense of powerlessness and a sense of blame gave rise to feelings of betrayals and shameful inadequacy. By sharing their inadequacy with co-workers, they managed to endure the sense of their inadequacy which otherwise would have threatened to paralyse them. Finding consolation in sharing wearing feelings, becoming realistic and attesting their worthiness, they reached reconciliation and found confirmation of being good enough. The findings are interpreted in light of Lögstrup's ethics of trust, according to which conscience alerts us to silent but radical ethical demand and the risk of self-deception.     

Disaster response: The University of Texas School of Nursing experience

Nurses comprise the largest group of health-care providers and should be key partners for any disaster response in their community. An often untapped resource in many communities is the contingent of nurse faculty, staff and students in schools of nursing across the country. In an effort to provide guidance on how schools and colleges of nursing link with their community and provide real-world experience for students, the present paper: (i) outlines how a Memorandum of Cooperation between the City of Austin and the University of Texas at Austin was created; and (ii) describes an example of how a school of nursing could become organized to respond to a community's call for help.     

A narrative inquiry: moving on from homelessness for individuals with a major mental illness

This narrative study explores the experience of 'moving on' from homelessness for individuals with major mental illnesses, after they have obtained permanent housing with supports. Twelve participants were interviewed up to three times over 6 months. There were various routes to homelessness, participants were homeless for varying lengths of time, and they described different journeys of 'moving on' in their lives. Place, and a series of places, were central for participants in this experience. The experience of homelessness for many could be described as 'on the move', in a circular pattern from shelter to shelter or street. Permanent housing and supports allowed participants to 'move on', reconnecting with family, getting jobs and planning for the future. Several participants wanted their stories used to send messages of hope, courage and survival. This study highlights the need for nurses to be aware of the concept of 'place' in the process of recovery from mental illness.