World Health Day 2001: minding the world's mental health.
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Global Health↗
Biomedical subjects
R Jenkins
Publications and source records attributed to R Jenkins.
Glioblastoma-related gene mutations and over-expression of functional epidermal growth factor receptors in SKMG-3 glioma cells.
Amplification of the epidermal growth factor receptor (EGFR) gene is found in about 40% of glioblastomas (GBMs) but is rarely detected in GBM cell lines. We confirmed that the exceptional SKMG-3 GBM cell line retained amplified EGFR genes in vitro, and found that these sequences were concentrated on extra-chromosomal DNA particles similar to double-minute chromosomes. The cells contained two other gene mutations that are associated with high-grade astrocytic tumors: extra-chromosomal amplification of the cyclin-dependent kinase-4 (CDK4) gene and a homozygous mutation within the PTEN tumor suppressor gene. Immunoblots revealed very high levels of EGFR, moderately increased expression of CDK4, and no detectable PTEN protein. The overexpressed SKMG-3 EGFRs responded to exogenous ligand and resembled normal rather than mutant receptors. A heterozygous mutation of the p53 gene (p53R282W) correlated with failure of radiation to induce the expression of cyclin-dependent kinase inhibitor p21waf1 or an early G1 cell cycle arrest. Although each of these gene mutations occurs in GBMs, SKMG-3 cells had an unusual genotype in that a p53 gene mutation co-existed with amplified EGFR genes. Nonetheless, the SKMG-3 cell line can be exploited as a model to study how oncogenic EGFR signals in GBM cells interact with over-expressed CDK4 and loss of PTEN to confer the malignant phenotype.
Blotting, Southern↗
A general population comparison of the Composite International Diagnostic Interview (CIDI) and the Schedules for Clinical Assessment in Neuropsychiatry (SCAN).
BACKGROUND: In psychiatric surveys of the general population, there has been considerable discrepancy between diagnoses obtained by fully structured interviews and those established by systematic semi-structured clinical evaluation. The Composite International Diagnostic Interview (CIDI) is an example of the first type of interview widely used in general population surveys. We compared its performance in diagnosing current depressive and anxiety disorders with the Schedules for Clinical Assessment in Neuropsychiatry (SCAN), a semi-structured diagnostic interview administered by clinically trained interviewers. METHODS: Household addresses in Leicestershire, UK, were randomly sampled and 860 adults were screened with the Revised Clinical Interview Schedule. Adults with too few symptoms to fulfil diagnostic criteria for study disorders were excluded to increase the proportion re-interviewed who met such criteria. Repeat diagnostic interviews with the CIDI and SCAN, ordered randomly, were sought from eligible screen positive respondents. Recalibrated CIDI prevalence estimates were derived from the SCAN classification using Bayesian statistics. RESULTS: Concordance ranged between 'poor' and 'fair' across almost all types of study disorders, and for co-morbidity. Concordance was somewhat better for severity of depression and when lower diagnostic thresholds were used for depression. Interview order effects were suggested with lower concordance when CIDI followed SCAN. Recalibration reduced the prevalence of depressive or anxiety disorder from 9.0 to 6.2%. CONCLUSIONS: Community psychiatric surveys using structured diagnostic interview data must be interpreted cautiously. They should include an element of clinical re-appraisal so findings can be adjusted for estimation differences between fully structured and clinical assessments.
Adolescent↗
The impact of personality disorder in UK primary care: a 1-year follow-up of attenders.
BACKGROUND: The usefulness of the concept of personality disorder has not been properly tested outside psychiatric services. We set out to examine this in primary care, by examining the ability of the diagnosis to predict health status and patterns of service use. METHOD: A cohort of consecutive attenders, who had previously been rated for the presence of personality disorder using a standardized assessment, was followed-up at 1 year. The participating general practitioners also rated the personalities of, and their attitudes towards, a proportion of this sample of attenders. RESULTS: After adjusting for the effects of all covariates, a rating of personality disorder (generated by the standardized assessment) was associated with frequent attendance to general practice and fewer referrals to secondary care. A GP rating of personality disorder was associated with the prescription of psychotropic medication. The level of agreement between a GP rating of personality disorder and the standardized assessment was poor. GPs rated personality disorder more frequently in participants who were perceived to be less compliant, less likeable and more stressful to deal with. Participants with a psychiatric rating of personality disorder did not attract these negative perceptions. CONCLUSIONS: Personality disorder, as rated by a research interview, is a predictor of health service usage. There is a significant disparity between a research rating of personality disorder and the diagnostic ratings made by GPs. The GP ratings of personality disorder were strongly associated with adverse perceptions of the patient's consulting behaviour.
Adult↗
Making psychiatric epidemiology useful: the contribution of epidemiology to government policy.
OBJECTIVE: This paper aims to discuss the contribution of epidemiology to aspects of public policy that have either a direct influence on mental health and mental disorders, or an indirect effect by influencing environmental factors which influence mental health. Both kinds of public policy will need to be considered by governments wishing to protect, promote and improve the mental health of their populations. The paper draws on information from both relatively wealthy and low-income countries. METHOD: The paper defines epidemiology and mental health policy, sets out the range of government policies which may have an impact on mental health, and explores the ways in which epidemiology may contribute to mental health policy in relation to service inputs, processes and outcomes as well as to wider government policies. The paper also examines the advantages and disadvantages of different sources of data. RESULTS: There are a number of reasons to carry out large-scale surveys of psychiatric morbidity. First, effective policy should address the needs of the population, which can best be assessed by the epidemiology and the social and economic causes and consequences of psychiatric morbidity. Secondly, representative information in a defined geographic area can document the use of existing services and can estimate the extent of unmet needs and the services required meeting those needs. Thirdly, valid information on prevalence and associated risk factors of presumed causal importance allow aetiological hypotheses to be generated and tested and models developed for prevention. Finally, by repeating community surveys, it is possible to monitor the health of the population and trends. Epidemiological findings emphasize the importance of mental health policy addressing the key role of primary care, the social context and social consequences of disorder, the importance of addressing services for children, the need to reduce premature mortality from suicide and from physical illness. Epidemiological findings show that mental health and mental disorders are related to the environment both in its structural physical sense and in the sense of the social processes connected to and influenced by particular settings. Thus epidemiology can contribute to general policies on employment and unemployment, housing and homelessness, education and women's issues. CONCLUSION: Mental health policy is increasingly recognized as an essential area for countries wishing to enhance their economic, social and human capital. Epidemiological data are a basic prerequisite to informing such policies. Expert professional and epidemiological advice to ministries is essential if policy is to be rooted in the evidence for population needs, risk factors, effective treatments and services, and measurement of outcomes. It is therefore important to develop the capacity for policy work in the psychiatric profession by including public health, epidemiology and policy placements for young psychiatrists.
Child↗
Preliminary results of a liver allocation plan using a continuous medical severity score that de-emphasizes waiting time.
Liver allocation remains problematic because current policy prioritizes status 2B or 3 patients by waiting time rather than medical urgency. On February 21, 2000, we implemented a variance to the United Network for Organ Sharing liver allocation policy that redefined status 2A by much more rigid, definable criteria and prioritized status 2B patients by using a continuous medical urgency score based on the Child-Turcotte-Pugh score and other medical conditions. In this system, waiting time is used only to differentiate status 2B candidates with equal medical urgency scores. Comparing the 6-month period (period 1; n = 67) before implementation of this system to the 6-month period after implementation (period 2; n = 75), there was a significant reduction in the number of transplantations performed for patients listed as status 2A (46.3% to 14.7%; P =.002) and an increase in the number of patients listed as status 2B who received transplants (44.8% to 70.7%; P =.10). Most dramatically, there was a 37.1% reduction in overall deaths on the waiting list from 94 deaths in period 1 to 62 deaths in period 2 (P =.005), with the most significant reduction for patients removed from this list at status 2B (52 v 18 patients; P =.04). There were 3 postoperative deaths in each period, with only 1 graft lost in period 2. Status 2B patients with the greatest degree of medical urgency received transplants without multiple peer reviews requesting elevation to 2A status. We conclude that a continuous medical urgency score system allocates donor livers much more fairly to those in medical need and reduces waiting list mortality without sacrificing efficacy.
Health Care Rationing↗
Life-threatening hypophosphatemia after right hepatic lobectomy for live donor adult liver transplantation.
Life-threatening hypophosphatemia (phosphorus < 1.0 mg/dL) has been reported only once after liver resection for tumor and was associated with a significant increase in postoperative complications. Hypophosphatemia is associated with reversible cardiac dysfunction, hypoventilation, and impaired immunity. The purpose of this study was to determine the incidence of hypophosphatemia after elective right hepatic lobectomy for live donor adult liver transplantation (LDALT), investigate the associated complication rate and surgical outcome of live liver donors, and determine the efficacy of prospective treatment with phosphate repletion as part of total parenteral nutrition (TPN). Evaluation of 30 donors who provided 30 right-lobe grafts between December 1998 and January 2000 was performed. Of the initial 18 live liver donors (group 1), 10 donors were treated with TPN that contained slightly more (35 +/- 8 mmol/d) than the recommended daily allowance (RDA) of phosphorus (30 mmol/d) starting on postoperative day 1. The last 12 donors (group 2) were prospectively studied and administered similar TPN with 2 times the RDA for phosphorus (60 mmol/d). All donors in group 1 developed hypophosphatemia that was either life threatening (phosphorus < 1.0 mg/dL) in 70% or severely depleted (phosphorus, 1.5 to 1.1 mg/dL) in 30%. With more aggressive phosphate repletion (group 2), only 8% developed life-threatening (phosphorus < 1.0 mg/dL) hypophosphatemia and 30% developed severe (phosphorus, 1.1 to 1.5 mg/dL) hypophosphatemia. Results suggest that hypophosphatemia is a universal event after LDALT and may have contributed to the observed complications in this study. Repletion of phosphorus at twice the RDA abrogates the incidence of hypophosphatemia and may reduce donor morbidity. Institutions performing LDALT should carefully monitor live liver donors for hypophosphatemia and correct abnormal phosphate levels. Additional studies are needed to determine whether more aggressive parenteral repletion can prevent postoperative hypophosphatemia and thus improve outcomes.
Adult↗
Ex-vivo product performance of Diskus and Turbuhaler inhalers using inhalation profiles from patients with severe chronic obstructive pulmonary disease.
Dosing performance of dry powder inhalers is dependent on patient's inspiratory effort. This study compares the inhalation profiles generated by patients with severe obstructive lung disease using Diskus and Turbuhaler inhalers. The patient profiles are subsequently used to determine the dosing performance of fluticasone propionate Diskus and budesonide Turbuhaler inhalers. Inhalation profiles were recorded in COPD patients (FEV1 < or = 30% predicted) as they inhaled with maximal effort through the inhalers. The profiles were used in an inhalation simulator to assess the dosing performance by measuring the total emitted dose and the fine particle mass for each inhaler type. Peak inspiratory flow was significantly higher through the Diskus (mean 82.31 min(-1)) compared with Turbuhaler (mean 53.51 min(-1), difference = 28.8 l min(-1); P < 0.0001). In addition, in direct comparison of the two devices. the Diskus was shown to deliver a more consistent dose irrespective of flow than the Turbuhaler in this patient population. These findings may be of importance in optimising selection of devices for patients with severe airway obstruction.
Aged↗
International Conference on Health Research for Development (COHRED), Bangkok, Thailand, October 9-13, 2000: report on the symposium on traditional medicine, October 9, 2000.
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Guidelines as Topic↗
The Satisfaction with Information about Medicines Scale (SIMS): a new measurement tool for audit and research.
OBJECTIVE: To develop and examine the psychometric properties of the Satisfaction with Information about Medicines Scale (SIMS), a new 17-item tool designed to assess the extent to which patients feel they have received enough information about prescribed medicines. METHODS: Patients from eight diagnostic categories were recruited at hospitals in London and Brighton and completed the SIMS questionnaire during hospital admission or attendance at outpatient clinic appointments. The SIMS was evaluated in terms of its ease of use, internal consistency, test-retest reliability, and criterion related validity using existing self-report measures of adherence and patient beliefs about medicines. RESULTS: The SIMS was well accepted by patients in a variety of clinical settings and showed satisfactory internal consistency and test-retest reliability. As predicted, higher levels of satisfaction with medicines information were associated with higher levels of reported adherence, and lower levels of satisfaction were associated with stronger concerns about the potential adverse effects of medicines, providing evidence of criterion related validity. CONCLUSION: The SIMS performed well on a number of psychometric indicators and shows promise as a tool for audit (measuring patients' satisfaction with information about their prescribed medicines), research (evaluating current or new forms of information provision), and clinical practice (identifying the information needs of individual patients and as an aid to planning medicine related consultations).
Drug Information Services↗
Nicotine, alcohol and drug dependence and psychiatric comorbidity. Results of a national household survey.
BACKGROUND: There is a well-recognised relationship between substance use disorders and other psychiatric disorders. This relationship has been well documented in a range of population-based studies. AIMS: This study aims to report on consumption patterns of and dependence on nicotine, alcohol and non-prescribed drugs and to report on the levels of psychiatric morbidity in these groups. METHOD: A national household study of psychiatric morbidity was conducted in England and Wales. Psychiatric assessment was based on the Clinical Interview Schedule-Revised (CIS-R). Measures of nicotine, alcohol and drug use and dependence were obtained. This paper compares the levels of psychiatric morbidity in the non-dependent and the nicotine-, alcohol- and drug-dependent cases. RESULTS: Twelve per cent of the non-dependent population were assessed as having any psychiatric disorder compared with 22% of the nicotine-dependent, 30% of the alcohol-dependent and 45% of the drug-dependent population. CONCLUSIONS: There is a clear relationship between dependence on nicotine, alcohol and drugs and other psychiatric morbidity.
Adolescent↗
Identification of androstenedione in a river containing paper mill effluent.
Effluent from a paper mill discharging into the Fenholloway River, Taylor County, Florida, USA, contains chemicals that masculinize females of the resident population of eastern mosquitofish (Gambusia holbrooki), as evidenced in females by elongated anal fins, which is normally a male-specific trait. To identify androgenic components in the effluent, water collected from the Fenholloway River and a control tributary was fractionated using solid-phase extraction and reverse-phase high-performance-liquid chromatography. Two Fenholloway River fractions induced androgen receptor-dependent transcriptional activity in transient transfection cell culture assays. Of these, androstenedione was confirmed by liquid chromatography-mass spectrometry with multiple reaction monitoring.
Androstenedione↗
Detection of ventricular enlargement in patients at the earliest clinical stage of MS.
The aim of this study was to determine whether atrophy could be detected at the earliest clinical stages of MS. Patients were selected from a 1-year follow-up MRI study of clinically isolated syndromes. Nine patients who developed MS were compared with eight matched patients who had no further symptoms. Significant ventricular enlargement occurred in the group that developed MS but not in the other group. Our findings show that atrophy, albeit mild, can be detected early in the course of MS.
Adolescent↗
Progressive cerebral atrophy in MS: a serial study using registered, volumetric MRI.
OBJECTIVE: To assess the potential of registered volumetric MRI in measuring rates of atrophy in MS. BACKGROUND: Pathologic and imaging studies suggest that the development of permanent neurologic impairment in MS is associated with progressive brain and spinal cord atrophy. Atrophy has been suggested as a potential marker of disease progression. Conventional atrophy measurements requiring manual outlining are time-consuming and subject to reproducibility problems. Registration of serial MRI may offer a useful alternative in that cerebral losses may be measured directly from automated subtraction of brain volumes. METHODS: Twenty-six patients with MS and 26 age- and gender-matched controls had two volumetric brain MR studies 1 year apart. Baseline brain and ventricular volumes were measured using semiautomated techniques, and follow-up scans were registered to baseline. Rates of cerebral atrophy were calculated directly from the registered scans. RESULTS: Baseline brain volumes in the MS group were smaller (mean difference 78 mL [95% CI 13 to 143; p = 0.02]) and ventricular volumes greater (mean difference 12 mL [95% CI 6 to 18; p < 0.001]) than controls. The rate of cerebral atrophy in the MS group (0.8% per year) was over twice that of controls (0.3%), and the rate of ventricular enlargement was five times greater than the controls (1.6 versus 0.3 mL/year). CONCLUSION: Progressive cerebral atrophy is an important feature of MS. Registration-based measurements are sensitive and reproducible, allowing progressive atrophy to be detected within 1 year and may have potential as a marker of progression in monitoring therapeutic trials.
Adult↗
Intracranial volume and Alzheimer disease: evidence against the cerebral reserve hypothesis.
BACKGROUND: Total intracranial volume (TIV) measurement commonly is used to correct for variations in premorbid brain size in imaging studies of cerebral structures in Alzheimer disease (AD). This assumes no intrinsic difference in TIV between patients and control subjects and that TIV measurements are unaffected by cerebral atrophy. However, an autopsy study has suggested that a larger premorbid brain may protect against AD onset. A recent computed tomographic study lent support to this by finding a correlation between intracranial size and age at onset of AD in women. OBJECTIVE: To investigate the relationship between TIV and sporadic and familial AD. DESIGN: Retrospective case study. SETTING: Specialist dementia clinic. PATIENTS: Eighty-five patients with AD and 52 healthy volunteers. MAIN OUTCOME MEASURES: Age at symptom onset and TIV measured using a semiautomatic interactive thresholding technique on magnetic resonance imaging spanning the entire intracranial cavity. RESULTS: Reproducibility measurement was high (intrarater coefficient of variation, 1.2%; interrater coefficient of variation, 0.7%). Unlike brain atrophy in the patients with AD, TIV did not vary over time. Mean TIV did not differ significantly between any of the subject groups. There was no association between TIV and age or age at symptom onset. The only significant predictor of TIV was sex. CONCLUSIONS: Measurements of TIV are independent of atrophy and can be used safely to adjust for differences in head size in studies of cerebral structure in AD. Premorbid brain size does not differ between patients with familial and sporadic AD and controls and does not delay disease onset.
Adult↗
Loss of expression of the DRR 1 gene at chromosomal segment 3p21.1 in renal cell carcinoma.
Consistent deletion of DNA sequences in chromosomal band 3p21 observed in a variety of human tumors suggests the presence of one or more tumor suppressor genes within this region. Previously, we reported on the construction of two distinct cosmid contigs and our identification of several new genes within 3p21.1. In our search for tumor suppressor genes from this region, we have cloned a gene that we have called DRR 1 (downregulated in renal cell carcinoma). The gene was first mapped to 3p21.1 by fluorescence in situ hybridization analysis. Further analysis of yeast artificial chromosome clones in 3p14.2-p21.1 refined its localization. DRR 1 spans about 10 Kb of genomic DNA with a 3.5-Kb mature transcript. The putative protein encoded by this gene is 144 amino acids and includes a nuclear localization signal and a coiled domain. The gene showed loss of expression in eight of eight renal cell carcinoma cell lines, one of seven ovarian cancer cell lines, one of one cervical cancer cell line, one of one gastric cancer cell line, and one of one non-small-cell lung cancer cell line. Southern blot analysis did not show any altered bands, indicating that gross structural changes or deletions did not cause the loss of expression. This gene was also found to have reduced expression in 23 of 34 paired primary renal cell carcinomas. Mutational analysis detected three polymorphic sites within the gene, but no point mutations were identified in the 34 primary tumors. However, we did detect base substitutions in 4 of 12 cell lines that had undetectable expression of the gene. We also transfected the gene into DRR 1-negative cell lines and observed clear growth retardation. Our results suggest that loss of expression of the DRR 1 gene may play an important role in the development of renal cell carcinoma and possibly other tumors. Genes Chromosomes Cancer 27:1-10, 2000.
Amino Acid Sequence↗
Psychiatric disorder and dysfunction in the UK National Survey of Psychiatric Morbidity.
BACKGROUND: Psychiatric symptoms are wide-spread in the general population, but have little effect on performance. Deficits in performance and psychiatric symptoms may be the end point of processes common to both, or they may be caused by quite different factors. In this paper we examine the epidemiological distribution of psychiatric symptoms and performance deficits, as indicated by difficulties in activities of daily living (ADL). We hypothesised that ADL difficulties are partly independent of psychiatric symptoms, and that this is reflected in a different demographic distribution. METHOD: The household component of the National Surveys of Psychiatric Morbidity was based on a sample of around ten thousand subjects selected at random from the population of Great Britain. Psychiatric symptoms were elicited by lay interviewers using the revised Clinical Interview Schedule. Performance was assessed by asking about difficulties experienced in performing seven types of everyday activity. In this paper, our chosen variables were overall symptom and ADL deficit scores, and these were related to standard demographic variables. RESULTS: There were significant differences in the epidemiological distribution of psychiatric symptoms and ADL difficulties. In particular, men experienced more ADL difficulties at a given symptom level than women. There were also differences in relation to social class, employment status, marital status, ethnic group and age. CONCLUSIONS: ADL deficits and psychiatric symptoms are related in the general population, and this probably represents common factors in their origin. However, discrepancies in the social distribution of these phenomena suggest there are also aetiological differences. These do not appear to be the result of the impact of physical illness on activities of daily living. Our results emphasise that ADL difficulties should be studied separately, particularly in investigations of treatment seeking.
Activities of Daily Living↗
Concomitant oncoprotein detection with fluorescence in situ hybridization (CODFISH): a fluorescence-based assay enabling simultaneous visualization of gene amplification and encoded protein expression.
We sought the validation of a three-color fluorescence-based system that simultaneously profiles Her2/neu oncogene copy by fluorescence in situ hybridization (FISH) and Her-2/neu encoded protein by the use of a versatile alkaline phosphatase chromogen fast red K in either fluorescence or bright-field mode. Nuclei were counterstained with DAPI. Nineteen infiltrating ductal carcinomas of breast were comprehensively evaluated for Her-2/neu amplification/overexpression by direct and indirect FISH using digoxigenin (DigFISH) and direct fluorescently labeled probes, autoradiographic RNA:RNA in situ hybridization, and immunohistochemistry using monoclonal antibody CB11. CODFISH results correlated well with DigFISH, direct-label FISH, mRNA expression, and oncoprotein expression as assessed with CB11, and enabled simultaneous visualization of gene copy and protein. In addition, qualitative immunohistochemistry may be followed by CODFISH gene copy enumeration to clarify ambiguous cases.
Antibodies, Monoclonal↗