Risk factors for transition to first episode psychosis among individuals with 'at-risk mental states'

Recently developed criteria have been successful at identifying individuals at imminent risk of developing a psychotic disorder, but these criteria lead to 50-60% false positives. This study investigated whether measures of family history, peri-natal complications, premorbid social functioning, premorbid personality, recent life events and current symptoms would be able to improve predictions of psychosis in a group of young, help-seeking individuals who had been identified as being at risk. Individuals (N=74) were followed up at least 1 year after initial assessment. Half the sample went on to develop a psychotic disorder. The most reliable scale-based predictor was the degree of presence of schizotypal personality characteristics. However, individual items assessing odd beliefs/magical thinking, marked impairment in role functioning, blunted or inappropriate affect, anhedonia/asociality and auditory hallucinations were also highly predictive of transition, yielding good sensitivity (84%) and specificity (86%). These predictors are consistent with a picture of poor premorbid functioning that further declines in the period up to transition.     

Attitudes and roles of general practitioners in the treatment of schizophrenia compared with community mental health staff and patients

Abstract. Background: Most general practitioners (GPs) are currently treating a small number of patients with schizophrenia; however, little is known about GPs experiences in this area. This paper examines the attitudes and roles of Australian GPs in the treatment of schizophrenia and their relationships with specialist services. Methods: A total of 192 GPs ratings of possible sources and forms of help for patients with schizophrenia were compared with the ratings of 50 mental health services (MHS) staff and 129 patients. Comparisons within the health professionals were also made in relation to diagnostic and treatment confidence, perceived roles, and typical problems encountered. Results: Perceived helpfulness ratings were reasonably consistent across groups. However, patients tended to rank close family members as more helpful. GPs and MHS staff reported complementary roles, with a shared responsibility for early detection and relapse prevention. Treatment compliance, and communication and accessibility to specialist agencies were identified as major problems. Conclusions: GPs fulfil a valuable role in the treatment of schizophrenia, which could be enhanced through improved training. Mental health services need to work more effectively with GPs in treating schizophrenia and acknowledge their complementary roles.     

An evaluation of psychiatric support to magistrates' courts

A Court Protocol was introduced to Hampshire Magistrates' Courts on 1 January 2003 which enabled magistrates to seek information on mentally disordered defendants from local mental health workers in place of requesting a full psychiatric report. The scheme was evaluated by examining 48 case files of mentally-disordered defendants who were referred between 1 January 2003 and 31 December 2003. It was found that its use had significantly reduced the time taken from first appearance to disposal and significantly reduced inappropriate referrals to consultant psychiatrists. In many cases, defendants were spared repeated bail adjournments and lengthy remands in prison.     

Is ultrasound really helpful in the detection of rib fractures?

OBJECTIVE: To determine the usefulness of ultrasound in the detection of rib fractures. PATIENTS AND METHODS: A prospective study was performed over a 3-month period. Patients presenting with a high clinical suspicion of rib fracture(s) to the Accident and Emergency Department were referred for radiological work-up with a PA chest radiograph, an oblique rib view and a chest ultrasound. Associated lesions, e.g. pleural effusion, splenic laceration and pneumothorax were recorded. RESULTS: Fourteen patients were radiologically assessed. The mean patient age was 31 years (range 16-55 years) and the M:F ratio 3.7:1 (11 men and 3 women). Ten patients displayed a total of 15 broken ribs. Chest radiography detected 11, oblique rib views 13 and ultrasound 14 broken ribs. Ultrasound findings included discontinuity of cortical alignment in 12 fractures, an acoustic linear edge shadow in nine and a reverberation artifact in six. Concordance with plain film findings, and especially oblique rib views, was good, though better when the rib fractures fragments were markedly displaced. One splenic laceration was detected with an associated small pleural effusion. There were no pneumothoraces. The average time of ultrasound examination was 13 min. CONCLUSION: Ultrasound does not significantly increase the detection rate of rib fractures, may be uncomfortable for the patient and is too time-consuming to justify its routine use to detect rib fractures.     

Acute allergic reaction due to the administration of fibrinolytic therapy for ST-segment elevation myocardial infarction: case report and discussion

Although a rare phenomenon, acute allergic reactions to fibrinolytic and heparin therapy have been described in the literature. We report the case of a 63-year-old woman who experienced a severe anaphylactic reaction while undergoing fibrinolytic therapy with tissue plasminogen activator for an ST-segment elevation myocardial infarction. Overall outcome was successful, but patient morbidity was increased because of the reaction and the subsequent therapy administered.     

Pharmacokinetics of alemtuzumab used for in vivo and in vitro T-cell depletion in allogeneic transplantations: relevance for early adoptive immunotherapy and infectious complications

Persistence of alemtuzumab at lympholytic concentrations after reduced-intensity conditioning allogeneic stem cell transplantations (RITs) could impair immune reconstitution and reduce donor T-cell-mediated graft-versus-leukemia/lymphoma (GVL) effects, derived from the graft or subsequent adoptive immunotherapy. We have studied the pharmacokinetics of alemtuzumab in 2 different groups: RIT (100 mg alemtuzumab in vivo over 5 days) and myeloablative allografts (20 mg alemtuzumab added in vitro to the stem cells prior to return). Alemtuzumab concentrations in RIT patients were in excess of that required to kill infused donor CD52+ cells at the time of transplantation and remained at potentially lympholytic levels (> 0.1 microg/mL) for approximately 56 days after transplantation, 26 days longer than for the myeloablative group. Total lymphocyte counts were significantly lower in the RIT group persisting beyond 6 months after transplantation (P =.005), and median absolute CD4 counts higher than 200 x 106/L were delayed until 9 months after transplantation.     

Therapeutic LMP1 polyepitope vaccine for EBV-associated Hodgkin disease and nasopharyngeal carcinoma

Development of an epitope-based vaccination strategy designed to enhance Epstein-Barr virus (EBV)-specific CD8(+) cytotoxic T lymphocytes (CTLs) is increasingly being considered as a preferred approach for the treatment of EBV-associated relapsed Hodgkin disease (HD) and nasopharyngeal carcinoma (NPC). EBV-encoded latent membrane proteins, LMP1 and LMP2, are the only target antigens available for therapeutic augmentation of CTL responses in patients with HD and NPC. Here, we describe preclinical studies using a recombinant poxvirus vaccine that encodes a polyepitope protein comprising 6 HLA A2-restricted epitopes derived from LMP1. Human cells infected with this recombinant polyepitope construct were efficiently recognized by LMP1-specific CTL lines from HLA A2 healthy individuals. Furthermore, immunization of HLA A2/K(b) mice with this polyepitope vaccine consistently generated strong LMP1-specific CTL responses to 5 of the 6 epitopes, which were readily detected by both ex vivo and in vitro assays. More important, this polyepitope vaccine successfully reversed the outgrowth of LMP1-expressing tumors in HLA A2/K(b) mice. These studies provide an important platform for the development of an LMP-based polyepitope vaccine as an immunotherapeutic tool for the treatment of EBV-associated HD and NPC.     

Evidence for altered vascular responses to exogenous endothelin-1 in patients with advanced cirrhosis with restoration of the normal vasoconstrictor response following successful liver transplantation

BACKGROUND AND AIMS: There is evidence that dampened responses to endogenous vasoconstrictors contribute to the hyperdynamic circulation that is characteristic of advanced cirrhosis. The aim of this study was to determine whether there is an altered vascular responsiveness to the endothelium derived constricting factor endothelin-1 (ET-1) in patients with decompensated chronic liver disease which might contribute to this abnormal circulatory state, and whether normal endothelin responses are restored following liver transplantation. METHODS: Using forearm plethysmography, we studied the vascular response to an intra-arterial ET-1 infusion in six patients with end stage cirrhosis, before and after liver transplantation, compared with six normal control subjects. Responses to the selective endothelin A (ET(A)) receptor subtype antagonist, BQ123, were also examined. RESULTS: The forearm vessels of patients with cirrhosis vasodilated in response to ET-1 infusion while in healthy controls a marked vasoconstriction response was observed (p<0.0001, area under the curve time-blood flow was normal compared with the cirrhosis groups, ANOVA). Prior to commencement of liver transplant surgery, cirrhotic patients were confirmed to have a hyperdynamic circulation with a high cardiac index (4.07 (0.23) l/min/m(2) (normal range 2.8-3.6 l/min/m(2))) and low systemic vascular resistance index (1284 (115) dynxs/cm(5)/m(2) (normal range 1760-2600 dynxs/cm(5)/m(2))). Following transplantation, normal vasoconstrictor responses to ET-1 were restored. Responses to BQ123 were not different in patients with advanced cirrhosis compared with controls. CONCLUSION: In patients with end stage cirrhosis, ET-1 produces vasodilatation at a dose that causes marked vasoconstriction in normal control subjects. This effect is not attributable to impairment of ET(A) receptor responses. Our findings suggest that altered endothelin responses may contribute to the generalised dilatation of the circulation that occurs in patients with advanced liver disease.