bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antitumor activity of rituximab plus thalidomide in patients with relapsed/refractory mantle cell lymphoma
Authors: Kaufmann Hannes , Raderer Markus , Wöhrer Stefan , Püspök Andreas , Bankier Alexander , Zielinski Christoph , Chott Andreas , Drach Johannes 
Published: June 2004

AbstractWe evaluated a treatment strategy targeting both lymphoma cells (by rituximab) and the microenvironment (by thalidomide) in 16 patients with relapsed/refractory mantle cell lymphoma (MCL). Rituximab was administered at 375 mg/m2 for 4 weekly doses concomitantly with thalidomide (200 mg daily, with a dose increment to 400 mg on day 15), which was continued as maintenance therapy until progression/relapse. Thirteen patients (81%) experienced an objective response, with 5 complete responders (31%). Median progression-free survival (PFS) was 20.4 months (95% confidence interval [CI], 17.3-23.6 months), and estimated 3-year survival was 75%. In patients achieving a complete response, PFS after rituximab plus thalidomide was longer than PFS after the preceding chemotherapy. Severe adverse events included 2 thromboembolic events and 1 grade IV neutropenia associated with thalidomide. Our results suggest that rituximab plus thalidomide has marked antitumor activity in relapsed/refractory MCL and a low toxicity profile, which warrants further evaluation in MCL.
Bystander destruction of hematopoietic progenitor and stem cells in a mouse model of infusion-induced bone marrow failure
Authors: Chen Jichun , Lipovsky Karen , Ellison Felicia M. , Calado Rodrigo T. , Young Neal S. 
Published: June 2004

AbstractInfusion of parental lymph node (LN) cells into sublethally irradiated hybrid F1 recipients created a murine model for bone marrow (BM) failure. Affected animals developed fatal pancytopenia within 2 to 3 weeks, accompanied by BM oligoclonal T-cell infiltration and severe marrow hypoplasia indicated by approximately 10-fold declines in total BM cellularity, 15-fold declines in BM Lin-Sca1+c-Kit+ cells, 100-fold declines in spleen colony-forming units, and 100-fold declines in hematopoietic progenitor and stem cells as estimated by irradiation protection in vivo. LN cells of both H2b/b and H2d/d haplotypes were effectors. Serum interferon-γ (IFN-γ) concentration increased 2- to 3-fold. Marrow cells were severely apoptotic, with high proportions of Fas+ and annexin V+ cells. Cotransplantation of 5 × 105 BM cells from clinically affected donors and 106 BM cells from H2 identical healthy mice could not rescue lethally irradiated recipients. Recipients had significantly lower cellularity in peripheral blood and BM, and cell mixtures failed to produce a stromal feeder layer to support marrow cell growth in vitro. Pathogenic T cells from donors after BM failure appeared capable of destroying hematopoietic progenitor, stem, and stromal cells from fully compatible healthy donors as “innocent bystanders.” This effect can be partially abrogated by anti-IFN-γ antibody. (Blood. 2004;104:1671-1678)
Constitutive activation of the MEK/ERK pathway mediates all effects of oncogenic H-ras expression in primary erythroid progenitors
Authors: Zhang Jing , Lodish Harvey F. 
Published: June 2004

AbstractOncogenic mutations in ras genes frequently occur in patients with myeloid disorders, and in these patients erythropoiesis is often affected. Previously, we showed that expression of oncogenic H-ras in purified mouse primary fetal liver erythroid progenitors blocks terminal erythroid differentiation and supports erythropoietin (Epo)-independent proliferation. As a first step in understanding the underlying molecular mechanisms we examined the signaling pathways downstream of Ras in primary erythroid cells. We found that 3 major pathways are abnormally activated by oncogenic H-ras: Raf/ERK (extracellular signal-regulated kinase), phosphatidyl inositol 3 (PI3)-kinase/Akt, and RalGEF/RalA. However, only constitutive activation of the MEK (MAPK [mitogen-activated protein kinase]/ERK kinase)/ERK pathway alone could recapitulate all of the effects of oncogenic H-ras expression in blocking erythroid differentiation and inducing Epo-independent proliferation. Although expression of a constitutively active Akt kinase (ca.Akt) in erythroid progenitors does not significantly affect erythroid differentiation in the presence of Epo, coexpression of ca.Akt together with a constitutively active MEK causes prolonged Epo-independent proliferation of erythroid progenitors in addition to a block in differentiation. Moreover, the effects of oncogenic H-ras expression on primary erythroid cells are blocked by the addition of U0126, a specific inhibitor of MEK1 and MEK2, allowing normal terminal erythroid proliferation and differentiation. Our data suggest that the interruption of constitutive MEK/ERK signaling is a potential therapeutic strategy to correct impaired erythroid differentiation in patients with myeloid disorders. (Blood. 2004;104: 1679-1687)
Somatoform disorders in general practice
Authors: De Waal Margot W M. , Arnold Ingrid A. , Eekhof Just A. H. , Van Hemert Albert M. 
Published: June 2004

BackgroundGeneral practitioners play a pivotal part in the recognition and treatment of psychiatric disorders. Identifying somatoform disorders is important for the choice of treatment.AimsTo quantify the prevalence of, and functional impairment associated with, somatoform disorders, and their comorbidity with anxiety/depressive disorders.MethodTwo-stage prevalence study: a set of questionnaires was completed by 1046 consecutive patients of general practitioners (aged 25–80 years), followed by a standardised diagnostic interview (SCAN 2.1).ResultsThe prevalence of somatoform disorders was 16.1% (95% CI 12.8-19.4). When disorders with only mild impairment were included, the prevalence increased to 21.9%. Comorbidity of somatoform disorders and anxiety/depressive disorders was 3.3 times more likely than expected by chance. In patients with comorbid disorders, physical symptoms, depressive symptoms and functional limitations were additive.ConclusionsOur findings underline the importance of a comprehensive diagnostic approach to psychiatric disorders in general practice.
Prevalence of chronic disabling fatigue in children and adolescents
Authors: Farmer Anne , Fowler Tom , Scourfield Jane , Thapar Anita 
Published: June 2004

BackgroundThe epidemiology of chronic fatiguing illnesses in young people is poorly understood.AimsTo estimate the lifetime prevalence of different definitions of chronic fatigue in 8-to 17-year-olds.MethodParticipants came from two population-based twin series. Parents completed self-report questionnaires that enquired whether either child had ever experienced more than a few days of disabling fatigue. Telephone interviews were undertaken for individuals who had experienced such an episode.ResultsQuestionnaires were returned by 1468 families (65% response rate) and telephone interviews were undertaken regarding 99 of the 129 subjects (77%) who had experienced fatigue. The lifetime prevalence estimates ranged from 2.34% (95% CI 1.75–2.94) for disabling fatigue lasting 3 months to 1.29% (95% CI 0.87–1.71) for a disorder resembling adult operationally defined chronic fatigue syndrome.ConclusionsFrom the age of 11 years, young people have similar rates and types of chronic fatiguing illnesses to adults.
Age of traumatisation as a predictor of post-traumatic stress disorder or major depression in young women
Authors: Maercker Andreas , Michael Tanja , Fehm Lydia , Becker Eni S. , Margraf Jürgen 
Published: June 2004

BackgroundFindings in developmental psychopathology suggest that traumatisation in childhood may increase the risk of both post-traumatic stress disorder (PTSD) and major depressive disorder, whereas traumatisation in adolescence is more likely to lead to elevated PTSD risk.AimsTo estimate the impact of traumatisation in childhood or adolescence in a community sample.MethodA representative sample of 1966 young women from Dresden aged 18–45 years were interviewed for occurrence of traumatic events and the onset of PTSD and major depression. The sample was subdivided into a childhood trauma group (trauma up to age 12 years) and an adolescent trauma group (trauma from age 13 years).ResultsA quarter of all participants reported traumatic events meeting the DSM AI criterion. In the childhood group conditional risks for PTSD and major depressive disorder were 17.0% and 23.3%, respectively, compared with risks of 13.3% and 6.5%, respectively, in the adolescent group. In 29% of those with PTSD, major depression was also present.ConclusionsThe risk of developing major depressive disorder after traumatisation in childhood is approximately equal to the risk of developing PTSD. After age 13 years, the risk of PTSD is greater than the risk of major depression after traumatisation.
Hippocampal volume change in depression: Late- and early-onset illness compared
Authors: Lloyd Adrian J. , Ferrier I. Nicol , Barber Robert , Gholkar Anil , Young Allan H. , O'Brien John T. 
Published: June 2004

BackgroundEvidence for structural hippocampal change in depression is limited despite reports of neuronal damage due to hypercortisolaemia and vascular pathology.AimsTo compare hippocampal and white matter structural change in demographically matched controls and participants with early-onset and late-onset depression.MethodHigh-resolution volumetric magnetic resonance imaging (MRI) and rating of MRI hyperintensities.ResultsA total of 51 people with depression and 39 control participants were included. Participants with late-onset depression had bilateral hippocampal atrophy compared with those with early-onset depression and controls. Hippocampal volumes did not differ between control participants and those with early-onset depression. Age of depression onset correlated (negatively) with hippocampal volume but lifetime duration of depression did not. Hyperintensity ratings did not differ between groups.ConclusionsResults suggest that acquired biological factors are of greater importance in late-than in early-onset illness and that pathological processes other than exposure to hypercortisolaemia of depression underlie hippocampal atrophy in depression of late life.
Hypothalamic-pituitary-adrenal axis function in patients with bipolar disorder
Authors: Watson Stuart , Gallagher Peter , Ritchie James C. , Ferrier I. Nicol , Young Allan H. 
Published: June 2004

BackgroundHypothalamic-pituitary-adrenal (HPA) axis function, as variously measured by the responses to the combined dexamethasone/ corticotrophin-releasing hormone (dex/ CRH) test, the dexamethasone suppression test (DST) and basal cortisol levels, has been reported to be abnormal in bipolar disorder.AimsTo test the hypothesis that HPA axis dysfunction persists in patients in remission from bipolar disorder.MethodSalivary cortisol levels and the plasma cortisol response to the DST and dex/CRH test were examined in 53 patients with bipolar disorder, 27 of whom fulfilled stringent criteria for remission, and in 28 healthy controls. Serum dexamethasone levels were measured.ResultsPatients with bipolar disorder demonstrated an enhanced cortisol response to the dex/CRH test compared with controls (P=0.001). This response did not differ significantly between remitted and non-remitted patients. These findings were present after the potentially confounding effects of dexamethasone levels were accounted for.ConclusionsThe dex/CRH test is abnormal in both remitted and non-remitted patients with bipolar disorder. Thismeasure of HP Aaxis dysfunction is a potential trait marker in bipolar disorder and thus possibly indicative of the core pathophysiological process in this illness.
Effects of long-term prolactin-raising antipsychotic medication on bone mineral density in patients with schizophrenia
Authors: Meaney Anna Maria , Smith Shubulade , Howes O. D. , O'Brien Moira , Murray Robin M. , O'Keane Veronica 
Published: June 2004

BackgroundHigh rates of osteoporosis in schizophrenia may result from the prolactin-raising effects of some antipsychotic medication.AimsTo examine bone mineral density in relation to relevant endocrine variables in patients with schizophrenia taking prolactin-raising antipsychotics.MethodFifty-five patients who had been receiving prolactin-raising antipsychotic medication for > 10 years underwent dual-energy X-ray absorptiometry of their lumbar and hip bones. Among the endocrine variables assessed were plasma prolactin and sex hormones.ResultsAge-related reduced bone mineral density measures were found in 17 (57%) of the male and 8 (32%) of the female patients. Higher doses of medication were associated with increased rates of both hyperprolactinaemia and bone mineral density loss. Bone loss for the whole group was correlated with medication dose, and for men was inversely correlated with testosterone values.ConclusionsThese results suggestthat patients with schizophrenia on long-term prolactin-raising antipsychotic medication are at high risk of developing reduced bone mineral density as a consequence of hyperprolactinaemia-induced hypogonadism.
Non-adherence to antipsychotic medication regimens: Associations with resource use and costs
Authors: Knapp Martin , King Derek , Pugner Klaus , Lapuerta Pablo 
Published: June 2004

BackgroundSeveral factors are thought to influence resource use and costs in treating schizophrenia.AimsTo assess the relative impact of non-adherence and other factors associated with resource use and costs incurred by people with schizophrenia.MethodSecondary analyses were made of data from a 1994 national survey of psychiatric morbidity among adults living in institutions in the UK. Factors potentially relating to resource use and costs were examined using two-part models.ResultsPatients who failed to adhere to their medication regimen were over one-and-a-halftimes as likely as patients who did adhere to it to report use of in-patient services. Non-adherence is one of the most significant factors in increasing external service costs, by a factor of almost 3. Non-adherence predicted an excess annual cost per patient of approximately $2500 for in-patient services and over $5000 for total service use.ConclusionsResource use and costs are influenced by various factors. Medication non-adherence consistently exhibits an association with higher costs. Further important factors are patient needs and the ability of the system to address them.
Premorbid, psychosocial and clinical predictors of the costs of schizophrenia and other psychoses
Authors: Carr Vaughan J. , Lewin Terry J. , Neil Amanda L. , Halpin Sean A. , Holmes Scott 
Published: June 2004

BackgroundPredictors of the costs of psychosis have received insufficient research attention, particularly factors associated with indirect costs.AimsTo identify the predictors of direct mental health care costs and indirect or time-loss costs in psychotic disorders and to discuss their implications for future interventions.MethodStructured interview data from the Low Prevalence Disorders Study (n=980) were used to examine predictors of the costs of psychosis in Australia. Estimates of annual costs per patient were derived from the perspectives of government and society. Hierarchical regressions were used to assess the contributions to costs of premorbid, psychosocial and clinical factors.ResultsSchizophrenia involved greater costs than other psychotic disorders. Non-completion of high-school education and chronicity of illness course were predictive of higher costs across all categories, and some factors were linked primarily with mental health care costs (e.g. age at onset, current symptomatology) or indirect costs (e.g. male gender, overall disability).ConclusionsSeveral concurrent strategies were recommended, including early intervention programmes and assertive evidence-based rehabilitation and supported employment programmes aimed at reducing disability The cost-effectiveness of these approaches needs to be evaluated from the perspectives of both government and society.
Utilising survey data to inform public policy: Comparison of the cost-effectiveness of treatment of ten mental disorders
Authors: Andrews Gavin , Issakidis Cathy , Sanderson Kristy , Corry Justine , Lapsley Helen 
Published: June 2004

BackgroundMental health survey data are now being used proactively to decide how the burden of disease might best be reduced.AimsTo study the cost-effectiveness of current and optimal treatments for mental disorders and the proportion of burden avertable by each.MethodData for three affective, four anxiety and two alcohol use disorders and for schizophrenia were compared in terms of cost, burden averted and efficiency of current and optimal treatment. We then calculated the burden unavertable given current knowledge. The unit of health gain was a reduction in the years lived with disability (YLDs).ResultsSumming across all disorders, current treatment averted 13% of the burden, at an average cost of AUS$30 000 per YLD gained. Optimal treatment at current coverage could avert 20% of the burden, at an average cost of AUS$18 000 per YLD gained. Optimal treatment at optimal coverage could avert 28% of the burden, at AUS$16 000 per YLD gained. Sixty per cent of the burden of mental disorders was deemed to be unavertable.ConclusionsThe efficiency of treatment varied more than tenfold across disorders. Although coverage of some of the more efficient treatments should be extended, other factors justify continued use of less-efficient treatments for some disorders.
Melancholia and the probability and lethality of suicide attempts
Authors: Grunebaum Michael F. , Galfalvy Hanga C. , Oquendo Maria A. , Burke Ainsley K. , Mann J. John 
Published: June 2004

SummaryWe compared suicide attempts associated with melancholic v. non-melancholic major depression in 377 patients. Controlling for depression severity and other covariates, melancholia at baseline assessment was associated with more serious past suicide attempts and with the probability of suicide attempt during follow-up.
Do patients really want copies of their GP letters? A questionnaire survey of older adults and their carers
Authors: Dale Jenny , Tadros George , Adams Susan , Deshpande Nikhila 
Published: June 2004

Aims and MethodThe National Health Service Plan stated that all correspondence between clinicians would be copied to patients by April 2004. We wanted to find out whether this practice reflected the true desires of their patients. A questionnaire survey was therefore performed in older adults and their carers attending a psychiatric out-patient clinic.ResultsA total of 88 participants were recruited; 50 patients and 38 carers. The majority of patients and carers wanted a letter about their care but most preferred a separate, simple letter rather than a copy of the letter sent to their general practitioner.Clinical ImplicationsAlthough this study supports the existing evidence that patients would like written information about their care, it indicates that certain patient groups might not want this in the form of copies of their medical correspondence. Further research into patient and carer preference is needed before the implementation of this policy.
Female psychiatrists' career development after flexible training
Authors: Mears Alex , Etchegoyen Alicia , Stormont Fiona , Kendall Tim , Katona Cornelius , Pajak Sarah 
Published: June 2004

Aims and MethodThe project gathered data from a cohort of 300 flexibly trained female consultants in psychiatry in order to understand how their careers had progressed since the completion of their training. A postal questionnaire was used to gather this information.ResultsThese consultants were generally satisfied with their training, and were succeeding in pursuing their careers. Flexible training was developed to enable people with family commitments to train in psychiatry, and this is what it is being used for.Clinical ImplicationsFlexible training is an important avenue for an increasing number of psychiatrists to continue in their profession. With the current shortfall in consultant numbers, flexible training should be maintained and developed, and should be seen as a useful route to a consultant position.
Survey of staff attitudes to smoking in a large psychiatric hospital
Authors: Stubbs Jean , Haw Camilla , Garner Liz 
Published: June 2004

Aims and MethodThe aim of this survey was to examine staff views on smoking at work in a large psychiatric hospital. A postal questionnaire was sent to all clinical staff (n=1471) asking about their smoking habits and attitudes to smoking at work.ResultsThe response rate was 40.7%. Overall, 22.0% of respondents were smokers, with unqualified nursing staff having the highest rate (31.0%). The majority of staff did not favour a total ban on smoking by staff, patients or visitors. Smoking habit and profession influenced responses. Smokers and nurses were more permissive in their attitude towards smoking on wards than non-smokers and psychiatrists.Clinical ImplicationsImplementation of the government's recommendations on tobacco control in psychiatric units is likely to require considerable preparatory work with staff to ensure full compliance.
Who wants to do psychiatry?
Authors: Yakeley Jessica , Shoenberg Peter , Heady Austin 
Published: June 2004

Aims and MethodThe study aimed to determine whether medical students who participated in a student psychotherapy scheme aimed at helping them learn about the doctor-patient relationship were more likely to choose psychiatry as a career than a control group who did not participate. One hundred and ninety-eight medical students who participated in the University College and Middlesex School of Medicine (UCMSM) Psychotherapy Scheme between 1982 and 1992, and 200 randomly selected students of the same period who did not, were sent a questionnaire asking about career choice.ResultsSeventy-seven of 163 participants in the scheme who sent back the questionnaire had not thought about doing psychiatry before entering the scheme. Of these, 11 became psychiatrists (14.3%), compared with only two (1.6%) of the 128 controls (of 152 respondents) who had not considered psychiatry as a career at the same stage. This difference is highly significant (P<0.001). Many of the participants, including those who did not specialise in psychiatry, emphasised how the scheme had helped them understand the doctor-patient relationship.ImplicationsParticipating in the Student Psychotherapy Scheme encouraged medical students to choose psychiatry as a career. This knowledge is important, particularly in view of the current recruitment crisis in psychiatry.
Melatonin in the treatment of insomnia in children and adolescents
Authors: Armour David , Paton Carol 
Published: June 2004

Aims and MethodTo review the efficacy and safety of melatonin in the treatment of insomnia in children and adolescents, through a Medline search covering the years 1966 to November 2003.ResultsFive placebo-controlled studies and several case series were identified. Melatonin reduces sleep latency, but does not consistently improve other aspects of sleep disturbance. Safety, particularly in the medium- and long-term, is poorly evaluated; short-term concerns include exacerbation of epilepsy and asthma.Clinical ImplicationsMelatonin might be effective in the short-term treatment of sleep onset insomnia. The optimal dose is unknown. It cannot currently be recommended for the treatment of other forms of sleep disturbance or for routine long-term use. Melatonin is not a licensed medicine in the UK.