Late onset neutropenia with clozapine.
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Adult↗
Biomedical subjects
D Castle
Publications and source records attributed to D Castle.
The emergence of Stenotrophomonas maltophilia as a significant nosocomial pathogen at the University Hospital of the West Indies.
Stenotrophomonas maltophilia is emerging worldwide as a nosocomial pathogen. It is associated with certain risk factors and a wide range of infections. This study was done to document its emergence at the University Hospital of the West Indies and to determine the incidence, distribution and risk factors associated with it. A retrospective study was conducted over the period April 1997 to December 2000. Clinical records were available for 46 of the 66 patients identified over the study period. Fifty-five per cent of the cases came from the Intensive Care Unit (ICU) and the rest from other wards. There was a slight increase in the prevalence of infection with increasing age. The surgical service accounted for the largest number of isolates. Of the cases presented, 95.7% were exposed to a wide range of antibiotics and had some form of instrumentation. Underlying disease was found in 71.7% of the patients. S maltophilia was found most often in the sputum of ICU patients whereas it was most often isolated from wound swabs in the ward patients. The organism was isolated from blood more often in ICU patients (23.3%) than in ward patients (9.5%) and there was a 44% mortality rate among the cases in ICU compared with those on the wards (4.8%). Stenotrophomonas maltophilia is an important nosocomial pathogen and occurs in a wide cross-section of patients. The risk factors must be addressed and infection control measures implemented to restrict the spread of this organism.
Adolescent↗
Clinical challenges posed by new biotechnology.
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Biotechnology↗
Incidence of schizophrenia in south-east London between 1965 and 1997.
BACKGROUND: There has been much debate about changes in the incidence of schizophrenia. AIMS: To identify any changes in incidence of schizophrenia in Camberwell, south-east London, between 1965 and 1997. METHOD: Research Diagnostic Criteria and DSM-III-R diagnoses were generated for all first contacts by the OPCRIT computer program, and incidence rates of schizophrenia in seven time periods were measured. Indirect standardisation and Poisson models were used to measure the effect of time period and to examine interactions with age and gender. RESULTS: There was a continuous and statistically significant increase in the incidence of schizophrenia, which was greatest in people under 35 years of age and was not gender-specific. CONCLUSIONS: The incidence of schizophrenia has doubled in south-east London over the past three decades.
Adult↗
The use of seclusion in the year 2000: what has changed?
This study was undertaken to examine the perceptions of nurses working in three psychiatric settings regarding the effect and use of seclusion. It also aimed to identify current practices at these sites in the metropolitan area of Western Australia. A total of 78 nurses specialising in mental health care participated in the study by completing the 'Attitude towards seclusion survey'. The findings of this study indicate that nurses perceive seclusion as an accepted patient management strategy. The results also showed that the decision to seclude the patient was made by a senior mental health practitioner and that one hour was the average time a patient spent in seclusion. It is important to ensure that punishment, paternalistic attitudes or punitive actions are not part of clinical judgment regarding the use of seclusion. The study has provided evidence of nurses' perceptions concerning seclusion and the results highlight the need for staff to continue to explore and evaluate issues that lead to seclusion in order to facilitate the use of other management strategies that encourage a less restrictive environment.
Attitude of Health Personnel↗
A clinical validation of the Dysmorphic Concern Questionnaire.
OBJECTIVE: The current study addressed the concept of dysmorphic concern as a symptom that may exist in a number of disorders. The aims of the study were to: (i) validate a recently developed questionnaire that measures dysmorphic concern, the Dysmorphic Concern Questionnaire (DCQ); and (ii) evaluate the relationship of dysmorphic concern to depressed mood, social phobia, and obsessive-compulsive symptomatology. METHOD: Sixty-five psychiatric inpatients were diagnosed using the computerized version of the Composite International Diagnostic Interview (CIDI-A). They then completed the DCQ, and questionnaires measuring body dysmorphic disorder (the Body Dysmorphic Disorder Examination, or BDDE), depression, social phobia, and obsessive-compulsive disorder (OCD). The factor structure and convergent validity of the DCQ were determined, and associations with mood and anxiety symptoms explored. RESULTS: The DCQ was found to be a reliable and valid instrument that is sensitive to dysmorphic concern. Furthermore, although dysmorphic concern was associated with body dysmorphic disorder (BDD), depression, social phobia and OCD, only the score from the BDDE predicted DCQ score in a multiple regression analysis. Finally, BDD symptomatology was best defined by the presence of negative body beliefs as measured by the DCQ. CONCLUSIONS: Negative body beliefs are the hallmark of BDD. However, the existence of dysmorphic concern does not necessarily imply a diagnosis of BDD. The DCQ is a quick and efficient means of identifying dysmorphic concern in those who present with depression, OCD, social phobia or BDD.
Adolescent↗
Types of patients in a psychiatric intensive care unit.
OBJECTIVE: This paper reports the findings of a descriptive study of a patient population over a three-month period on an eight bed psychiatric intensive care unit (PICU) in Western Australia. The report provides a quantitative insight into the profile of patients in PICUs. It provides information on patients' diagnoses, presenting signs, symptoms and/or behaviours, legal codes assigned to patients, treatment interventions and management. METHOD: Data were collected prospectively from August to October 1999. A total of 122 patients were admitted to the PICU during the review period. Data were entered into an Access program then exported to SPSS (Version 9 for Windows) for analysis and frequency distributions were obtained. RESULTS: The results confirmed that the majority of patients admitted to the PICU were assessed as a high level of risk or needed containment. This finding is in line with the admission criteria developed by staff working in the PICU. It also supports the view that staff working in these units require expertise and confidence to communicate with and manage potentially aggressive and highly aroused patients. CONCLUSION: This study demonstrates the importance of ongoing evaluations of patient populations in promoting best practice initiatives in psychiatric care.
Adult↗
Comparison of the incidence of schizophrenia in rural Dumfries and Galloway and urban Camberwell.
BACKGROUND: Being born or living in urban areas is associated with high rates of schizophrenia. However, few studies have compared the incidence in urban/rural areas using the same methodology. AIMS: To compare service-based incidence rates for schizophrenia in rural Dumfries and Galloway in south-west Scotland with urban Camberwell in south-east London. METHOD: Using Research Diagnostic Criteria diagnoses from the OPCRIT computer algorithm, we compared the incidence of schizophrenia over 12 years (1979-1984 and 1992-1997) using indirect standardisation techniques and Poisson regression modelling. RESULTS: The incidence was 61% higher in urban Camberwell than in rural Dumfries and Galloway (standardised incidence ratio (SIR)=1.61; 95% CI=1.42-1.81). There was no difference in incidence when we compared the White population in Camberwell with Dumfries and Galloway (SIR=1.12; 95% CI=0.86-1.43). CONCLUSIONS: The incidence of schizophrenia in urban Camberwell was higher than that in rural Dumfries and Galloway; the high incidence of non-Whites in Camberwell largely explains the urban/rural difference.
Adolescent↗
Psychotic disorders in urban areas: an overview of the Study on Low Prevalence Disorders.
OBJECTIVE: This paper reports on a study designed within the framework of the National Survey of Mental Health and Wellbeing to: estimate the prevalence of psychoses in urban areas of Australia; identify profiles of symptomatology, impairments and disabilities; collect information on services received and needed; and explore quality of life issues in a broadly representative sample of people with psychotic illnesses. METHOD: The study was conducted over four areas in the Australian Capital Territory, Queensland, Victoria and Western Australia, as a two-phase survey: (i) a census and screening for psychosis of all individuals who made contacts with mental health services during a period of 1 month in 1997; and (ii) interviews with a stratified random sample (n=980) of the screen-positive individuals (n=3800) using a standardised instrument. RESULTS: The point prevalence (1 month) of psychotic disorders in the urban population aged 18-64 is in the range of 4-7 per 1000 with a weighted mean of 4.7 per 1000. People with psychotic disorders experience high rates of functional impairments and disability, decreased quality of life, persistent symptoms, substance-use comorbidity and frequent side effects of medication. Although the utilisation of hospital-based and community mental health services, as well as of public and non-governmental helping agencies, is high, the majority live in extreme social isolation and adverse socioeconomic circumstances. Among the many unmet needs, the limited availability of community-based rehabilitation, supported accommodation and employment opportunities is particularly prominent. CONCLUSIONS: The so-called 'low-prevalence' psychotic disorders represent a major and complex public health problem, associated with heavy personal and social costs. There is a need for a broad programmatic approach, involving various sectors of the community, to tackle the multiple dimensions of clinical disorder, personal functioning and socioeconomic environment that influence the course and outcome of psychosis and ultimately determine the effectiveness of service-based intervention.
Activities of Daily Living↗
A cognitive-behavioural, group-based intervention for social anxiety in schizophrenia.
OBJECTIVE: The objective of this study was to investigate the efficacy of group-based cognitive-behavioural therapy (CBT) for social anxiety in schizophrenia. METHOD: Patients with schizophrenia (20) with comorbid social anxiety were randomly assigned to the group-based CBT or wait-list control condition. Pre-, post- and 6-week follow-up ratings included measures of social anxiety and avoidance, mood and quality of life. RESULTS: The intervention group improved on all outcome measures and the control group showed no change in symptomatology. CONCLUSIONS: Group-based CBT is effective in treating social anxiety in schizophrenia.
Adult↗
The secretory carrier membrane protein family: structure and membrane topology.
Secretory carrier membrane proteins (SCAMPs) are integral membrane proteins found in secretory and endocytic carriers implicated to function in membrane trafficking. Using expressed sequence tag database and library screens and DNA sequencing, we have characterized several new SCAMPs spanning the plant and animal kingdoms and have defined a broadly conserved protein family. No obvious fungal homologue has been identified, however. We have found that SCAMPs share several structural motifs. These include NPF repeats, a leucine heptad repeat enriched in charged residues, and a proline-rich SH3-like and/or WW domain-binding site in the N-terminal domain, which is followed by a membrane core containing four putative transmembrane spans and three amphiphilic segments that are the most highly conserved structural elements. All SCAMPs are 32-38 kDa except mammalian SCAMP4, which is approximately 25 kDa and lacks most of the N-terminal hydrophilic domain of other SCAMPs. SCAMP4 is authentic as determined by Northern and Western blotting, suggesting that this portion of the larger SCAMPs encodes the functional domain. Focusing on SCAMP1, we have characterized its structure further by limited proteolysis and Western blotting with the use of isolated secretory granules as a uniformly oriented source of antigen and by topology mapping through expression of alkaline phosphatase gene fusions in Escherichia coli. Results show that SCAMP1 is degraded sequentially from the N terminus and then the C terminus, yielding an approximately 20-kDa membrane core that contains four transmembrane spans. Using synthetic peptides corresponding to the three conserved amphiphilic segments of the membrane core, we have demonstrated their binding to phospholipid membranes and shown by circular dichroism spectroscopy that the central amphiphilic segment linking transmembrane spans 2 and 3 is alpha-helical. In the intact protein, these segments are likely to reside in the cytoplasm-facing membrane interface. The current model of SCAMP1 suggests that the N and C termini form the cytoplasmic surface of the protein overlying a membrane core, which contains a functional domain located at the cytoplasmic interface with little exposure of the protein on the ectodomain.
Amino Acid Sequence↗
Risk factors for the deficit syndrome of schizophrenia.
Previous studies have found two risk factors associated with the deficit syndrome of schizophrenia: an increase in summer births, compared to others with schizophrenia; and a higher risk of schizophrenia in relatives. In data from the Camberwell Register Psychosis Series, a population-based sample that approximated a treated-incidence sample, the deficit/nondeficit categorization was made using a previously validated proxy method. Associations were found between the deficit syndrome and both summer birth and a family history of schizophrenia. In contrast, nondeficit schizophrenia was associated with a family history of psychiatric problems other than schizophrenia. The deficit group also had poorer insight. An early age of onset was associated with disorganization, but not with the deficit or nondeficit group. The deficit/nondeficit differences could not be attributed to confounding by demographic features or the severity of hallucinations, delusions, or formal thought disorder.
Age of Onset↗
Analyses of proteins involved in vesicular trafficking in platelets of mouse models of Hermansky Pudlak syndrome.
Hermansky Pudlak syndrome (HPS) is an autosomal recessive inherited disorder characterized by defects in synthesis and/or secretion of three related subcellular organelles: melanosomes, platelet-dense granules, and lysosomes. In the mouse, mutant forms of any of 14 separate genes result in an HPS-like phenotype. The mouse pearl and mocha genes encode subunits of the AP3 adaptor protein complex, confirming that HPS mutations involve proteins regulating intracellular vesicular trafficking. Therefore, expression of several additional proteins involved in vesicular transport was examined by immunoblotting of platelet extracts from HPS mutant and control mice. Platelet levels of SCAMPS (secretory carrier membrane proteins), Rab11, Rab31, NSF (N-ethylmaleimide-sensitive fusion protein), syntaxin 2, syntaxin 4, munc18c, and p115/TAP (p115/transcytosis-associated protein) were not significantly altered in several different HPS mutants. However, gunmetal (gm/gm) platelets contained decreased amounts of SNAP-23. The Snap23 gene was mapped to mouse chromosome 5, demonstrating it cannot encode the gm gene, which maps to chromosome 14. It is likely therefore that the gm gene functions upstream of SNAP-23 in vesicular trafficking.
Albinism, Oculocutaneous↗
Differences in distribution of ages of onset in males and females with schizophrenia.
An earlier age at onset of schizophrenia in men as opposed to women, has been widely reported, but hitherto, insufficient account has been taken of parameters that might confound this finding. Furthermore, few explanatory models have accounted for the differences in shape of the age-at-onset distributions in males and females with schizophrenia. A catchment area sample of 477 first contact cases with schizophrenia or related disorders was ascertained through a case register. Differences in age at onset distributions between males and females were determined, and adjustment made for potential confounding factors. The most powerful predictors of early illness-onset were poor premorbid occupational functioning, single marital status, and male sex. The earlier onset in males was robust to controlling for other parameters. The shape of the onset distribution also differed between the sexes: SKUMIX analysis revealed a two-peak distribution for males, and a three-peak distribution for females. The mean age at onset for schizophrenia is earlier in males, and the onset distribution differs between the sexes. Psychosocial variables cannot explain these findings. Possible explanations for these gender differences include males and females being differentially susceptible to subtypes of illness with different mean ages at onset; precipitating and/or ameliorating factors operating at different stages of life in males and females; and/or an X-linked susceptibility locus that determines the age at onset.
Age Factors↗
Relocation of the t-SNARE SNAP-23 from lamellipodia-like cell surface projections regulates compound exocytosis in mast cells.
For regulated secretion, mast cells and several other cell types utilize compound exocytosis, a combination of granule-plasma membrane and granule-granule fusions. The molecular machinery that controls this massive export process has not been identified. We report that SNAP-23, a t-SNARE related to SNAP-25, relocates in response to stimulation from plasma membrane lamellipodia-like projections to granule membranes in permeabilized mast cells. While relocation is a prerequisite for secretion, it can occur without membrane fusion and will expedite a subsequent secretory response. After relocation, SNAP-23 is required for exocytosis, implying a crucial role in promoting membrane fusion. Thus, relocation of this SNARE regulates compound exocytosis and links granule-plasma membrane and granule-granule fusions.
Animals↗
Sorting and storage during secretory granule biogenesis: looking backward and looking forward.
Secretory granules are specialized intracellular organelles that serve as a storage pool for selected secretory products. The exocytosis of secretory granules is markedly amplified under physiologically stimulated conditions. While granules have been recognized as post-Golgi carriers for almost 40 years, the molecular mechanisms involved in their formation from the trans-Golgi network are only beginning to be defined. This review summarizes and evaluates current information about how secretory proteins are thought to be sorted for the regulated secretory pathway and how these activities are positioned with respect to other post-Golgi sorting events that must occur in parallel. In the first half of the review, the emerging role of immature secretory granules in protein sorting is highlighted. The second half of the review summarizes what is known about the composition of granule membranes. The numerous similarities and relatively limited differences identified between granule membranes and other vesicular carriers that convey products to and from the plasmalemma, serve as a basis for examining how granule membrane composition might be established and how its unique functions interface with general post-Golgi membrane traffic. Studies of granule formation in vitro offer additional new insights, but also important challenges for future efforts to understand how regulated secretory pathways are constructed and maintained.
Animals↗