Elevated fatty acid amide hydrolase in the prefrontal cortex of borderline personality disorder: a [11C]CURB positron emission tomography study.

Amygdala-prefrontal cortex (PFC) functional impairments have been linked to emotion dysregulation and aggression in borderline personality disorder (BPD). Fatty acid amide hydrolase (FAAH), the major catabolic enzyme for the endocannabinoid anandamide, has been proposed as a key regulator of the amygdala-PFC circuit that subserves emotion regulation. We tested the hypothesis that FAAH levels measured with [11C]CURB positron emission tomography in amygdala and PFC would be elevated in BPD and would relate to hostility and aggression. Twenty BPD patients and 20 healthy controls underwent FAAH genotyping (rs324420) and scanning with [11C]CURB. BPD patients were medication-free and were not experiencing a current major depressive episode. Regional differences in [11C]CURB binding were assessed using multivariate analysis of covariance with PFC and amygdala [11C]CURB binding as dependent variables, diagnosis as a fixed factor, and sex and genotype as covariates. [11C]CURB binding was marginally elevated across the PFC and amygdala in BPD (p = 0.08). In a priori selected PFC, but not amygdala, [11C]CURB binding was significantly higher in BPD (11.0%, p = 0.035 versus 10.6%, p = 0.29). PFC and amygdala [11C]CURB binding was positively correlated with measures of hostility in BPD (r > 0.4; p < 0.04). This study is the first to provide preliminary evidence of elevated PFC FAAH binding in any psychiatric condition. Findings are consistent with the model that lower endocannabinoid tone could perturb PFC circuitry that regulates emotion and aggression. Replication of these findings could encourage testing of FAAH inhibitors as innovative treatments for BPD.

Congenital duplication of the larynx.

INTRODUCTION: The larynx is an intricate structure serving three important functions in humans: it protects the lower respiratory airway, facilitates respiration and helps produce sound through a key role in phonation. OBJECTIVE: We report the first published finding of congenital duplication of the larynx in a patient with previously cleared squamous cell carcinoma of the neck and a new diagnosis of squamous cell carcinoma of the lung. CASE REPORT: We describe the incidental finding of duplication of the larynx in a 62-year-old man with previously completely cleared squamous cell carcinoma of the neck, who presented with worsening dyspnoea. We also provide a brief overview of other published cases in which duplication of the vocal folds and epiglottis has been reported. RESULTS: Our patient experienced no symptoms related to this incidental finding of congenital duplication of the larynx. CONCLUSION: The first case of congenital duplication of the larynx is currently of academic interest only; however, the possible association with squamous cell carcinoma is postulated to raise awareness in clinicians who may observe further cases in the future.

Inquiries into homicides and serious violence perpetrated by psychiatric patients in New Zealand: need for consistency of method and result analysis.

BACKGROUND: The violent action of mentally ill people is a source of considerable public and professional concern. At times such incidents are subject to inquiry. In England and Wales, homicides by people suffering from mental illness are subject to mandatory external inquiry. Further, the Royal College of Psychiatrists coordinates a confidential research study into homicide and suicide by people in contact with mental health services. Inquiries have raised concern regarding widespread problems in mental health service delivery. Within New Zealand, similar concerns have been raised, but inquiries have been irregular and not of consistent methodology. The paper aims to review 10 years of inquiries into violent incidents to describe their methods, structure and findings. METHOD: All inquiries into violent actions perpetrated by patients in contact with mental health services between 1988 and 1998 and held by the Ministry of Health were reviewed. The nature of the inquiry, the incident, findings and recommendations were summarized. For each inquiry, an assessment was made as to whether the incident was predictable or preventable. RESULTS: There were 11 incidents leading to 13 inquiries, six of homicide, two of rape, one of the release of a dangerous patient and two in which a patient was shot by police. Two internal inquiries were followed by external inquiries. All inquiries found deficiencies of varying severity, the degree of deficiency being greater with external inquiries. Consistent criticisms related to skill, resource, coordination and communication failures. Two of the 11 inquiries found the incident to be 'predictable', and eight to have been 'preventable'. CONCLUSIONS: The problems in New Zealand are similar to those noted in England and Wales. Small numbers of inquiries make firm conclusions difficult, but the authors feel that a mandatory process of independent review of serious incidents is wise.

Prevalence of psychiatric disorders in New Zealand prisons: a national study.

OBJECTIVE: The paper describes the methodologies and results obtained on a large cohort of prison inmates in New Zealand who were screened for psychiatric disorder. METHOD: All women and remanded male inmates in New Zealand prisons, and a randomly selected cohort of 18% of sentenced male inmates were interviewed. Interviewers used the Composite International Diagnostic Interview - Automated to establish DSM-IV diagnoses, and the Personality Disorders Questionnaire to identify personality disorder. All prisons in New Zealand were visited. RESULTS: The results indicate markedly elevated prevalence rates for major mental disorder in the prison population when compared with community samples. This is especially the case for substance misuse, psychotic disorders, major depression, bipolar disorder, obsessive- compulsive disorder and posttraumatic stress disorder. Of particular concern is not only the increased prevalence rates for schizophrenia and related disorders but also the high level of comorbidity with substance misuse disorders demonstrated by this group. While 80.8% of inmates diagnosed with bipolar disorder were receiving psychiatric treatment in the prison, only 46.4% of depressed inmates and 37% of those suffering from psychosis were receiving treatment. Maori inmates were grossly overrepresented in the remand, female and male sentenced inmate population compared with the general population. CONCLUSIONS: A significant increase in provision of mental health services is required to cope with the high number of mentally ill inmates. The level of need demonstrated by this study requires a level of service provision that is quite beyond the capacity of current forensic psychiatry services, Department of Corrections Psychological Services or the prison nursing and medical officers. The elevated rates of common mental disorders argues for the use of improved psychiatric screening instruments, improved assessment and treatment capacities in the prison and an increased number of forensic psychiatric inpatient facilities to care for those psychotic inmates who are too unwell to be treated in the prison.

What is the role of procedural justice in civil commitment?

OBJECTIVE: To determine best practice management strategies in the clinical application of civil commitment. METHOD: All relevant literature on the topics of 'civil commitment', 'coercion' and 'procedural justice' were located on MEDLINE and PsychLIT databases and reviewed. Literature on the use of Ulysses contracts and advance directives in mental health treatment was integrated into the findings. RESULTS: Best practice evidence that guides management strategies is limited to the time of enactment of civil commitment. Management strategies involve enhancing the principles of procedural justice as a means of limiting negative patient perception of commitment. In the absence of evidence-based research beyond this point of enactment, grounds for the application of the principles of procedural justice are supported by reference to ethical considerations. Ulysses contracts provide an additional method for strengthening procedural justice. CONCLUSIONS: Procedural justice principles should be routinely applied throughout the processes of civil commitment in order to enhance longer term therapeutic outcomes and to blunt paternalism.

EMIT cyclosporine assay: development of an application protocol for Technicon AXON System.

Monitoring parent drug cyclosporine (CsA) concentrations in whole blood has been facilitated by the introduction of automated nonisotopic immunoassays [fluorescence polarization monoclonal whole blood assay (FPIA), EMIT Cyclosporine Assay]. The latter assay currently has a defined application only for Cobas Mira Chemistry Systems. The purpose of our work was to develop an application for this assay on the Technicon AXON. Instrument settings were optimized to arrive at the following assay performance characteristics. Limit of sensitivity was 50 micrograms/L. Interassay coefficients of variation (CV) were 11.2% (n = 16; mean = 81 micrograms/L) and 9.4% (n = 16; mean = 418 micrograms/L). Recoveries of 102, 112, and 117% were obtained by spiking aliquots of 10 whole blood patient pools of known CsA concentrations with 50, 100, and 200 micrograms/L CsA, respectively. Serial dilutions of two patient specimens demonstrated a linear relationship between expected and actual CsA concentrations (r = 0.996, 0.998; regression lines; y = 0.989x + 11.7; y = 0.979x + 9.5). Carryover and interference (lipemia) were not evident. Instrument calibration stability is at least 1 month. Comparison with CsA concentrations analyzed in renal transplant patients by the FPIA assay produced a linear regression equation of EMIT = 1.113x - 44.5, r = 0.968, Sy/x = 20.8, n = 32. Comparison with high-performance liquid chromatography (HPLC)-derived values in the same patient population produced a linear regression equation of EMIT = 1.114x - 16.4, r = 0.970, Sy/x = 20.2. FPIA-derived CsA concentrations averaged 14.2% more than those obtained with the EMIT method with the latter averaging 1.3% more than HPLC values.(ABSTRACT TRUNCATED AT 250 WORDS)

A comparison of cyclosporine assays using sequential samples from selected transplant patients.

The monitoring of cyclosporine (CsA) whole blood concentrations is an integral part of immunosuppressive treatment with this drug. Although such monitoring has been facilitated by the introduction of monoclonal immunoassay techniques, there is a paucity of published data comparing the assays longitudinally in selected patients. The purpose of our study was to co-evaluate two monoclonal immunoassays (Cyclosporine FPIA whole blood assay, Abbott Laboratories; Cyclo-Trac SP-whole blood RIA, Incstar Inc.) and a high-performance liquid chromatography (HPLC) technique for quantitating CsA in sequentially collected trough whole blood samples from 14 patients up to 75 days after renal (n = 6), heart (n = 3), and liver (n = 5) transplantation. HPLC CsA metabolite analyses (AM1, AM9, AM4N) were performed. Although CsA concentrations within most patients were significantly higher (p < 0.05, paired t test) when measured by both immunoassay techniques compared to HPLC, levels determined in three patients, (one liver, two renal) for the FPIA/HPLC comparison and one patient (liver) for the RIA/HPLC comparison were not significantly different (p > 0.05). CsA levels within nine patients were not significantly different (p > 0.05) when FPIA and RIA were compared, but results within three patients, (one liver, two renal) were significantly higher (p < 0.05) by RIA compared to FPIA, but results within one patient (heart) were significantly higher (p < 0.05) by FPIA. Our results demonstrate first that depending on the patient, HPLC-derived CsA results are not consistently lower than results generated by immunoassay techniques and second that CsA levels obtained by FPIA are statistically equivalent or in some patients, statistically less than RIA-derived levels.

Clozapine protocol: a collective approach to use of an unregistered medicine.

We describe a protocol for the use of an unregistered antipsychotic medicine, clozapine, in a mental health service. Traditionally, prescribing of unregistered medicines has been a matter between prescriber and patient alone. However, clozapine carries a high risk of agranulocytosis and its use requires strict adherence to monitoring procedures. Persons most likely to benefit from it include many who, because of their psychosis, may be unable to give truly informed consent or to react appropriately to adverse reactions. We have designed a protocol which seeks to ensure that this medicine is given only to those whose severity of illness and lack of response to all other reasonable treatment outweighs the risk of agranulocytosis, that it is used with maximum safety and that only persons who have been shown to benefit from the medicine continue to receive it after an initial trial. Although this protocol has been accepted by the medical staff, questions of clinical autonomy and liability in the event of medical misadventure remain.

Occurrence of Staphylococcus intermedius on the hair and skin of normal dogs.

Aerobic bacterial populations were studied on the distal hair coat and at the skin surface of the shoulder, rump and abdomen of 10 healthy dogs. Coagulase negative staphylococci (CNS) were more frequently isolated from the hair than the skin at the shoulder and rump. There was no difference in the isolation rate of coagulase positive staphylococci (CPS) (Staphylococcus intermedius) between the hair and skin. Total skin counts were greatest on the abdomen whereas CNS counts from the hair were least at this site. There were no differences between CPS counts at the three sites on either hair or skin. The populations on the relatively unfavourable microenvironment of the distal hair may represent contamination rather than colonisation. The low populations of CPS at the skin surface also indicate contamination or transient colonisation rather than true resident status.