Responding to self-harm in borderline personality disorder : from clinician frustration to therapeutic enquiry

Pessimistic attitudes and reactive behavioural management strategies act as a major barrier to effective service provision for patients with borderline personality disorder. This paper reviews research on countertransference reactions (negative professional attitudes) towards these patients and the professional response to the common presentation of self harm in this particular client group. The psychotherapeutic treatment of patients with borderline personality disorder is complex and both professionally and personally demanding. A clinical framework is proposed that enables clinicians to develop a more nuanced and empathic understanding of self harm within the context of personality disorder in order to facilitate enhanced therapeutic engagement with these challenging patients. A clinical case study illustrates the use of this framework and the potential for enhanced therapeutic management in conjunction with the recognition and reduction of clinician indifference and rejection, thus improving patient outcomes. (editor abstract)Pessimistic attitudes and reactive behavioural management strategies act as a major barrier to effective service provision for patients with borderline personality disorder. This paper reviews research on countertransference reactions (negative professional attitudes) towards these patients and the professional response to the common presentation of self harm in this particular client group. The psychotherapeutic treatment of patients with borderline personality disorder is complex and both professionally and personally demanding. A clinical framework is proposed that enables clinicians to develop a more nuanced and empathic understanding of self harm within the context of personality disorder in order to facilitate enhanced therapeutic engagement with these challenging patients. A clinical case study illustrates the use of this framework and the potential for enhanced therapeutic management in conjunction with the recognition and reduction of clinician indifference and rejection, thus improving patient outcomes.

Mechanism-based inhibition of cytochrome P450 3A4 by therapeutic drugs

Consistent with its highest abundance in humans, cytochrome P450 (CYP) 3A is responsible for the metabolism of about 60% of currently known drugs. However, this unusual low substrate specificity also makes CYP3A4 susceptible to reversible or irreversible inhibition by a variety of drugs. Mechanism-based inhibition of CYP3A4 is characterised by nicotinamide adenine dinucleotide phosphate hydrogen (NADPH)-, time- and concentration-dependent enzyme inactivation, occurring when some drugs are converted by CYP isoenzymes to reactive metabolites capable of irreversibly binding covalently to CYP3A4. Approaches using in vitro, in silico and in vivo models can be used to study CYP3A4 inactivation by drugs. Human liver microsomes are always used to estimate inactivation kinetic parameters including the concentration required for half-maximal inactivation (K(I)) and the maximal rate of inactivation at saturation (k(inact)).Clinically important mechanism-based CYP3A4 inhibitors include antibacterials (e.g. clarithromycin, erythromycin and isoniazid), anticancer agents (e.g. tamoxifen and irinotecan), anti-HIV agents (e.g. ritonavir and delavirdine), antihypertensives (e.g. dihydralazine, verapamil and diltiazem), sex steroids and their receptor modulators (e.g. gestodene and raloxifene), and several herbal constituents (e.g. bergamottin and glabridin). Drugs inactivating CYP3A4 often possess several common moieties such as a tertiary amine function, furan ring, and acetylene function. It appears that the chemical properties of a drug critical to CYP3A4 inactivation include formation of reactive metabolites by CYP isoenzymes, preponderance of CYP inducers and P-glycoprotein (P-gp) substrate, and occurrence of clinically significant pharmacokinetic interactions with coadministered drugs.Compared with reversible inhibition of CYP3A4, mechanism-based inhibition of CYP3A4 more frequently cause pharmacokinetic-pharmacodynamic drug-drug interactions, as the inactivated CYP3A4 has to be replaced by newly synthesised CYP3A4 protein. The resultant drug interactions may lead to adverse drug effects, including some fatal events. For example, when aforementioned CYP3A4 inhibitors are coadministered with terfenadine, cisapride or astemizole (all CYP3A4 substrates), torsades de pointes (a life-threatening ventricular arrhythmia associated with QT prolongation) may occur.However, predicting drug-drug interactions involving CYP3A4 inactivation is difficult, since the clinical outcomes depend on a number of factors that are associated with drugs and patients. The apparent pharmacokinetic effect of a mechanism-based inhibitor of CYP3A4 would be a function of its K(I), k(inact) and partition ratio and the zero-order synthesis rate of new or replacement enzyme. The inactivators for CYP3A4 can be inducers and P-gp substrates/inhibitors, confounding in vitro-in vivo extrapolation. The clinical significance of CYP3A inhibition for drug safety and efficacy warrants closer understanding of the mechanisms for each inhibitor. Furthermore, such inactivation may be exploited for therapeutic gain in certain circumstances.

Tolling for the luckless, the abandoned and forsaked : therapeutic jurisprudence and international human rights law as applied to prisoners and detainees by forensic psychologists

Objectives. There has been an explosion of interest in therapeutic jurisprudence as both a filter and lens for viewing the extent to which the legal system serves therapeutic or anti-therapeutic consequences. However, little attention has been paid to the impact of therapeutic jurisprudence on questions of international human rights law and the role of forensic psychologists. The paper aims to provide an intersection between human rights, therapeutic jurisprudence, and forensic psychology.

Method. Human rights are based on legal, social, and moral rules. Human rights literature generally considers legal rights but such policy statements do not provide principles to guide forensic psychologists in addressing moral or social rights. Therefore, a framework to guide forensic psychologists is required.

Conclusion. As duty-bearers, forensic psychologists need to address the core values of freedom and well-being in rights holders (in this instance, prisoners and detainees with a mental illness). The paper proposes that human rights principles can add to the normative base of a therapeutic jurisprudence framework, and in-turn, therapeutic jurisprudence can assist forensic psychologists to actively address human rights.

The effects of an apparent breach of therapeutic regulations on consumers: the Pan Pharmaceuticals recall

The aim of this study was to assess how demographic variables and personal values are related to people's knowledge and cognitive and behavioural responses towards a major drug recall event that occurred in Australia in 2003. For this purpose, a survey was sent out in 2003 to 1000 households in Victoria, Australia. Households had been randomly selected from the electoral role. A total of 415 respondents participated. Results indicated that higher socioeconomic status was related to better information about the recall event and more trust in manufacturers. Respondents who held traditional or naturalistic values were likely to trust that faults in the system would be regulated by the government or consumers themselves. Parents and older respondents were more likely to be critical of the Therapeutic Goods Administration which co-ordinated the recall. Parental status, education and values were related to subsequent changes in respondents' use of complementary medicines. In light of the worth of the health supplement industry to the Australian economy, the results of this survey suggest that the Therapeutic Goods Administration should adopt a more transparent and accountable role towards the public.

Protein kinase C isozymes as potential therapeutic targets in immune disorders

Background: Members of the protein kinase C (PKC) family are key signalling mediators in immune responses, and pharmacological inhibition of PKCs may be useful for treating immune-mediated diseases. Objective: To review and discuss the insights gained so far into various PKC isozymes and the therapeutic potential and challenges of developing PKC inhibitors for immune disorder therapy. Methods: A literature review of the role of PKCs in immune cell signalling and recent studies describing immune functions associated with PKC isozyme deficiency in relevant mouse disease models, followed by specific case studies of current and potential therapeutic strategies targeting PKCs. Results/conclusion: There is vast amount of data supporting PKC isozymes as attractive drug targets for certain immune disorders. Although the development of specific PKC isozyme inhibitors has been challenging, some progress has been made. It remains to be seen if broad-scale or isozyme-selective inhibition of PKC will have clinical efficacy.

Where the home in valley meets the damp dirty prison : a human rights perspective on therapeutic jurisprudence and the rule of forensic psychologists in correctional settings

The roles of forensic psychologists in coerced environments such as corrections include that of treatment provider (for the offender) and that of organizational consultant (for the community). This dual role raises ethical issues between offender rights and community rights; an imbalance results in the violation of human rights. A timely reminder of a slippery ethical slope that can arise is the failure of the American Psychological Association to manage this balance regarding interrogation and torture of detainees under the Bush administration. To establish a “bright-line position” regarding ethical practice, forensic psychologists need to be cognizant of international human rights law. In this endeavor, international covenants and a universal ethical code ought to guide practice, although seemingly unresolveable conflicts between the law and ethics codes may arise. A solution to this problem is to devise an ethical framework that is based on enforceable universally shared human values regarding dignity and rights. To this end, the legal theory of therapeutic jurisprudence can assist psychologists to understand the law, the legal system, and their role in applying the law therapeutically to support offender dignity, freedom, and well-being. In this way, a moral stance is taken and the forensic role of treatment provider and/or organizational consultant is not expected to trump the prescriptions and the proscriptions of the law.