Prevalence, correlates, and disability of personality disorders in the United States: results from the national epidemiologic survey on alcohol and related conditions

OBJECTIVE: To present nationally representative data on the prevalence, sociodemographic correlates, and disability of 7 of the 10 DSM-IV personality disorders. METHOD: The data were derived from the 2001-2002 National Epidemiologic Survey on Alcohol and Related Conditions (N = 43,093). Diagnoses were made using the Alcohol Use Disorder and Associated Disabilities Interview Schedule-DSM-IV Version, and associations between personality disorders and sociodemographic correlates were determined. The relationship between personality disorders and 3 emotional disability scores (Short-Form 12, version 2) was also examined. RESULTS: Overall, 14.79% of adult Americans (95% CI = 14.08 to 15.50), or 30.8 million, had at least 1 personality disorder. The most prevalent personality disorder in the general population was obsessive-compulsive personality disorder, 7.88% (95% CI = 7.43 to 8.33), followed by paranoid personality disorder 4.41% (95% CI = 4.12 to 4.70), antisocial personality disorder 3.63% (95% CI = 3.34 to 3.92), schizoid personality disorder 3.13% (95% CI = 2.89 to 3.37), avoidant personality disorder 2.36% (95% CI = 2.14 to 2.58), histrionic personality disorder 1.84% (95% CI = 1.66 to 2.02), and dependent personality disorder 0.49% (95% CI = 0.40 to 0.58). The risk of avoidant, dependent, and paranoid personality disorders was significantly greater among women than men (p <.05); the risk of antisocial personality disorder was greater among men compared with women (p <.05); and no sex differences were observed in the risk of obsessive-compulsive, schizoid, or histrionic personality disorders. In general, risk factors for personality disorders included being Native American or black, being a young adult, having low socioeconomic status, and being divorced, separated, widowed, or never married. Avoidant, dependent, schizoid, paranoid, and antisocial personality disorders (p <.02 to p <.0001) were each statistically significant predictors of disability. Obsessive-compulsive personality disorder was inconsistently related to disability. In contrast, disability was not significantly different among individuals with histrionic personality disorder compared with those without the disorder. CONCLUSION: Personality disorders are prevalent in the general population and are generally highly associated with disability. This study highlights the need to develop more effective and targeted prevention and intervention initiatives for personality disorders.     

Renal length and inulin clearance in the radiologically normal single kidney

Compensatory hypertrophy of a single functioning kidney is well described and has been shown to occur in utero. The long-term effects of hypertrophy and hyperfiltration in this situation are unknown. This study defined the growth parameters for single kidneys during childhood and correlated them with inulin clearance. Patients were those who had a radiologically "normal" single kidney, where the contralateral kidney was known to be non-functioning from infancy. Data were obtained from 74 children (40 boys and 34 girls) drawn from a registry of cases with a single kidney, and in whom simultaneous measurements of inulin clearance and renal length had been made at around 5, 10, and 16 years of age. Renal length was taken as the maximal bipolar measurement using real-time ultrasound scan. Inulin clearance was by continuous infusion technique. Nomograms for single kidney growth were determined against age, height, weight, and body surface area. Renal growth was correlated with inulin clearance. Renal length was found to correlate best with body surface area (r=0.85, P<0.001), but this was not significantly superior to correlations with age, height, or weight separately. Inulin clearance per body surface area correlated positively with standardized renal length, i.e., Z score for renal length normalized for body surface area (r=0.53, P<0.001). The larger kidneys have a higher glomerular filtration rate. Provided that the nephron number in the single kidney is similar to that in a paired kidney, single kidneys are hypertrophied and the single nephron glomerular filtration rate is likely to be abnormally high in these children.     

Inhibition of proliferation of PC3 cells by the branched-chain fatty acid, 12-methyltetradecanoic acid,is associated with inhibition of 5-lipoxygenase

BACKGROUND: Branched-chain fatty acids or fatty alcohols have been reported to possess anti-tumor activity in various tumor models. Here we study 12-methyltetradecanoic acid (12-MTA), a branched-chain fatty acid, isolated from a sea cucumber extract, on the growth of prostate cancer cells and investigate the underlying mechanisms of its effect. METHODS: 12-MTA was evaluated by MTT assay for its ability to inhibit cell proliferation in various cancer types. The ability of 12-MTA to induce apoptosis of PC3 cells was examined by morphologic changes, propidium iodide (PI) staining, and caspase-3 activation. Furthermore, alteration of eicosanoid metabolism by 12-MTA was examined in PC3 and RBL-1 cells and in purified lipoxygenase (LOX) and cyclooxygenase (COX) enzymes. RESULTS: 12-MTA inhibited proliferation of various cell lines, with IC50s ranging from 17.99 to 35.44 microg/ml. PI staining clearly showed that 12-MTA caused PC3 cell death through induction of apoptosis. At 50 microg/ml, 12-MTA increased caspase-3 activity four to seven-fold compared with that in control cells. Examination of cellular arachidonate metabolism showed that at 25 microg/ml, 12-MTA reduced the level of 5-hydroxyeicosatetraenoic acid (5-HETE) by 45%. Furthermore, exogenous 5-HETE protects PC3 cells from 12-MTA induced cell death. CONCLUSIONS: 12-MTA inhibited proliferation of cancer cells via apoptosis, in which caspase-3 may play a role. At relevant concentrations, 12-MTA can selectively inhibit the formation of 5-HETE, a metabolite of 5-lipoxygenase. This agent may be a novel adjunctive therapy for selected malignancies including prostate cancer.     

Management of early psychosis in a generic adult mental health service

OBJECTIVE: To evaluate current practice at a generic adult mental health service, St Vincent's Mental Health Service (SVMHS) in relation to management of patients with early psychosis. A further aim was to compare treatment of early psychosis patients within this generic service with management of a similar group in a specialized early psychosis service. METHOD: A case file audit of all patients identified as having early psychosis (within the first 2 years of treatment) was undertaken using a standardized audit tool. Variables including proportion of early psychosis admitted as inpatients to the psychiatric unit, average length of stay (LOS), use of seclusion, involvement of police in admission process, mean neuroleptic dose and estimated duration of untreated psychosis (DUP) were studied. Results of this audit were then compared with published evaluative data from the Early Psychosis Prevention and Intervention Centre (EPPIC), a service specifically catering for young people with early psychosis (within the first 18 months of treatment). RESULTS: Data were collected on 62 of 68 patients identified as having early psychosis. Within the generic service, mean DUP was found to be about 15 months, a high proportion (81%) of patients were admitted and secluded (22% of those admitted), average length of stay was 46.5 days and use of police in the admission process was also high (40% of those admitted). This compares unfavourably with the EPPIC data of mean DUP of just over 6 months, 64.1% of patients admitted, 10.3% secluded, average LOS 12.9 days, and police involved in 3.8% of admissions. CONCLUSIONS: We believe that practice at SVMHS in relation to early psychosis patients is fairly typical of management of these patients within generic services as a whole. These services tend to focus on the needs of the majority of their patients, those with chronic schizophrenia, rather than the small group of patients with early psychosis (who make up about 8% of current case-load at SVMHS). Failure to assertively assess and follow-up young people with early psychosis may contribute to long DUPs, which may in turn result in patients being more disturbed at time of initial treatment, thus requiring inpatient treatment and longer length of stay. Additionally, staff at generic services may not feel confident in managing early psychosis patients and may be unaware of the special needs of this patient group. These preliminary data suggest that generic services are not optimal for treatment of early psychosis patients and that treatment of early psychosis within them is not cost-effective.     

Working on the interface: identifying professional responses to families with mental health and child-care needs

The gaps between mental health and child-care services constitute a recognised barrier to providing effective services to families where parents have mental health problems. Recent guidance exhorts professionals to coordinate and collaborate more consistently in this area of work. The present study aimed to identify the barriers to inter-professional collaboration through a survey of 500 health and social care professionals. The views of 11 mothers with severe mental health problems whose children had been subject to a child protection case conference were also interrogated through two sets of interviews. The study found that communication problems were identified more frequently between child care workers and adult psychiatrists than between other groups. Communication between general practitioners and child-care workers was also more likely to be described as problematic. While there was some support amongst practitioners for child-care workers to assume a coordinating or lead role in such cases, this support was not overwhelming, and reflected professional interests and alliances. The mothers themselves valued support from professionals whom they felt were 'there for them' and whom they could trust. There was evidence from the responses of child-care social workers that they lacked the capacity to fill this role in relation to parents and their statutory child-care responsibilities may make it particularly difficult for them to do so. The authors recommend that a dyad of workers from the child-care and community mental health services should share the coordinating key worker role in such cases.     

Mutations in the AUH gene cause 3-methylglutaconic aciduria type I

The conversion of 3-methylglutaconyl-CoA to 3-hydroxy-3-methylglutaryl-CoA is the only step in leucine catametabolism yet to be characterized at enzyme and DNA levels. The deficiency of the putative mitochondrial enzyme 3-methylglutaconyl-CoA hydratase associates with the rare organic aciduria 3-methylglutaconic aciduria type I (MGA1), but neither the enzyme nor its gene have been described in any organism. Here we report that human 3-methylglutaconyl-CoA hydratase is identical with a previously described RNA-binding protein (designated AUH) possessing enoyl-CoA hydratase activity. Molecular analyses in five patients from four independent families revealed homozygosity or compound heterozygosity for mutations in the AUH gene; most mutations are predicted to completely abolish protein function. Mutations identified include c.80delG, R197X, IVS8-1G>A, A240V, and c.613_614insA. Clinical severity of MGA1 in published patients has been quite variable. Included in the present study is an additional patient with MGA1 who was detected by neonatal screening and has remained asymptomatic up to his present age of 2 years. The boy is homozygous for an N-terminal frameshift mutation in the AUH gene. Complete absence of 3-methylglutaconyl-CoA hydratase/AUH appears to be compatible with normal development in some cases. Further work is required to identify external or genetic factors associated with development of clinical problems in patients with MGA1.     

Young-onset Parkinson's disease: a guide to care and support

One in seven people diagnosed with Parkinson's disease will be aged less than 50 years. The medical management of young-onset Parkinson's disease is complicated and a multidisciplinary approach to care is vital to meet the psychological, emotional and social needs of people with Parkinson's disease and their carers.     

Management of giant cell arteritis. Our 27-year clinical study: new light on old controversies

Giant cell arteritis (GCA) is the prime medical emergency in ophthalmology because of its dreaded complication of visual loss in one or both eyes, which is preventable if these patients are diagnosed early and treated immediately and aggressively with systemic corticosteroids. However, there is much controversy on diagnostic criteria and various aspects of steroid therapy to prevent visual loss. We discuss in detail the reasons for the controversy, clinical criteria to establish a definite early diagnosis of GCA, and its management. To provide new information on corticosteroid therapy in GCA, we also present our 27-year planned study on steroid therapy in GCA in 145 temporal artery biopsy-confirmed GCA patients (96 with and 49 without visual loss) seen and followed for 6 weeks or more in our clinic. The median follow-up time was 2.43 years, with interquartile range of 1-6 years (range 6 weeks to 20.2 years). Intravenous megadose steroid therapy was initially given to 33% followed by oral steroids, while the rest had only the oral therapy. The median starting oral prednisone dose was 80 mg/day, with 40% on >/=100 mg/day. We found that the most reliable and sensitive parameters to regulate and taper down steroid therapy were the levels of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) and NOT systemic symptoms. All patients were maintained at the high-dose prednisone till both the ESR and CRP had stabilized at low levels (that usually took 2-3 weeks), after which very gradual tapering of prednisone was started, guided by the ESR and CRP levels only. The median time to reach the lowest maintenance dose of prednisone at which the ESR and CRP stayed low and stable was 48.7 months (95% CI: 34.6, 71.4 months), and the median lowest prednisone dose achieved was 7 mg/day (interquartile range of 1-16 mg/day). A comparison of patients with and without visual loss showed no significant difference in the time to attain the lowest dose (p = 0.359). Our study showed that no generalization is possible for tapering down of prednisone and there is no set formula because of the infinite variation between individuals. Only 10 (7 without visual loss, 3 with visual loss) of 145 patients were able to stop the therapy and maintain stable ESR and CRP levels. We found that only 4% of GCA patients with visual loss showed any visual improvement with high-dose steroid therapy, and 4% developed further visual loss during the first 5 days of high-dose steroid therapy but none after that. Our studies found no evidence that intravenous megadose steroid therapy was more effective than oral therapy in improving vision or preventing visual deterioration due to GCA.     

A dual mechanism of action of the anticancer agent F 11782 on human topoisomerase II alpha

F 11782 is a novel epipodophyllotoxin that targets eukaryotic topoisomerases and inhibits enzyme binding to DNA. While F 11782 has not been found to stabilize either topoisomerase I or topoisomerase II covalent complexes, drug treatment appears to result in DNA damage. F 11782 has also been shown to inhibit the DNA nucleotide excision repair (NER) pathway. Bisdioxopiperazine-resistant small cell lung cancer (SCLC) OC-NYH/Y165S and Chinese hamster ovary (CHO) CHO/159-1 cells having functional Y49F and Y165S mutations in the topoisomerase II alpha isoform were both resistant to F 11782. The catalytic activity of purified human Y50F and Y165S mutant topoisomerase II alpha (Y50F in the human protein corresponds to Y49F in the CHO protein) was likewise resistant to the inhibitory action of F 11782. F 11782 was also found to induce a non-covalent salt-stable complex of human topoisomerase II with DNA that was ATP-independent. F 11782 thus displays a dual mechanism of action on human topoisomerase II alpha, reducing its affinity for DNA while also stabilizing the protein bound in the form of a salt-stable complex. Our results suggest that topoisomerase II alpha is a target of F 11782 in vivo, and that F 11782 may act as a novel topoisomerase II poison.