Biomedical subjects

R Cochrane

Publications and source records attributed to R Cochrane.

At least 19 recordsLinked to original sources

PubMed2003

cAMP-mediated suppression of a Th1 clone associated with an alteration of the intracellular redox environment.

We have shown previously that the elevation of intracellular cAMP in antigen or anti-CD3-activated murine Th1 clones in the absence of antigen inhibits antigen-induced proliferation and the production of IL-2 by H2O2-mediated oxidation of p56lck and inhibits antigen-induced production of interferon-gamma by the induction of intracellular nitric oxide. Moreover, activated Th1 clones are resistant to cAMP-induced suppression. These results suggest that the immunosuppression of Th1 cells mediated by elevated intracellular cAMP is associated with an alteration in the intracellular oxidation/reduction environment. Here we report that the culture of an antigen or anti-CD3-activated murine Th1 clone with the adenylcyclase agonist forskolin (FSK) in the absence of antigen reduces the activity of intracellular catalase, and diminishes levels of intracellular reduced glutathione (GSH). Resting cells resistant to cAMP-induced suppression have higher intracellular GSH levels than antigen-activated cells susceptible to cAMP-induced suppression. The results provide further evidence that cAMP-induced suppression of Th1 clones is mediated by profound alterations in the intracellular redox environment and may be used to selectively inactivate Th1 cells activated by antigen.

Animals↗

PubMed2002

Performance on tests of frontal lobe function reflect general intellectual ability.

Recent studies have indicated that performance on tests of frontal lobe function are highly associated with general intellectual ability (g). Some authors have even claimed that the available evidence does not support a more specific account of frontal lobe function than to provide a general intellectual function for the performance of goal directed tasks. We examined the relationship between performance on the WAIS-R (as a measure of g) and performance on standard tests of frontal lobe function in 123 healthy individuals. Our results demonstrate that in healthy individuals (i) performance on the most popular tests of frontal lobe function shares significant variance, and (ii) a large proportion of that shared variance is highly associated with performance on the Wechsler Adult Intelligence Scales-Revised (WAIS-R), so that the tests are similar to the extent that they measure g. Performance on the Modified Card Sorting Test (MCST), however, is not related to g. The results support the claim that many tests of frontal lobe function measure primarily a non-specific intellectual function but also indicate that some tests, like the MCST, may be assessing more specific cognitive operations.

Adolescent↗

PubMed2001

Differential regulation of T cell receptor-mediated Th1 cell IFN-gamma production and proliferation by divergent cAMP-mediated redox pathways.

Culture of an H-2(s)-restricted, bovine myelin basic protein (BMBP)-specific murine Th1 clone with the adenyl cyclase agonist forskolin (FSK) or isobutylmethylxanthine (IBMX), an inhibitor of cAMP catabolism, before culture with anti-CD3 or BMBP and antigen-presenting cells (APC) suppressed antigen or anti-CD3-induced proliferation and production of interferon-gamma (IFN-gamma). Other H-2(s)-derived or H-2(b)-derived clones specific for BMBP or keyhole limpet hemocyanin (KLH) were similarly affected. FSK did not affect the expression of CD4 or the T cell receptor (TCR) but did diminish levels of the phosphorylated (activated) mitogen-activated protein (MAP) kinases early response kinase-1 (ERK-1) and ERK-2. Immunoblotting of lysates from an FSK-treated Th1 clone with antibodies to a carboxy-terminal epitope of p56(lck), a signal transduction enzyme upstream from ERK-1 and ERK2, did not detect p56(lck) unless the lysates were reduced prior to electrophoresis. Immunoblotting of nonreduced lysates with antibodies to an amino-terminal epitope demonstrated p56(lck) with a lower apparent molecular weight, characteristic of oxidized proteins. Reduction restored the detection of p56(lck) by anticarboxy-terminal p56(lck) and to mobilities indistinguishable from controls detected by the antiamino-terminal p56(lck). N-acetylcysteine or catalase prevented FSK-induced suppression of antigen-induced proliferation and the loss of carboxy-terminal epitopes of p56(lck). An inhibitor of cAMP-dependent protein kinase A (PKA) or nitric oxide synthase (NOS) did not affect FSK-induced inhibition of antigen-induced proliferation. In contrast, inhibitors of PKA or NOS, but not catalase, prevented FSK-induced suppression of IFN-gamma production. Moreover, immunoblots of lysates precipitated with anti-p56(lck), phosphotyrosine, or CD4 demonstrated that in FSK-treated, anti-CD3-stimulated cells, p56(lck) is not associated with CD4 zeta chain, nor is p56(lck) or zeta chain phosphorylated. In vitro kinase assays demonstrated that p56(lck) from FSK-treated cells does not have kinase activity. Taken together, the results suggest that an elevation of intracellular cAMP (in the absence of antigen) creates an oxidative environment that oxidizes and inactivates p56(lck) by an H(2)O(2)-dependent, PKA-independent mechanism and inhibits the production of IFN-gamma by an NO, PKA-dependent mechanism. Thus, antigen-induced proliferation and IFN-gamma production in a Th1 clone are controlled separately by different cAMP-dependent, redox-based mechanisms.

1-Methyl-3-isobutylxanthine↗

PubMed2000

Maternal and child psychological sequelae in paediatric burn injuries.

It is a commonly held belief that many children suffer psychological sequelae following burn injury. This six month controlled, prospective, follow up study was designed to investigate psychological sequelae in children and their mothers following paediatric burn injury. The study employed a sample of 40 children with burn injuries, and their mothers with three control groups, each of 40 children and their mothers: an acutely ill group, a fracture group and a non ill/injured group. Measures at initial contact and 6 month follow up included the Child Behaviour Checklist and the Hospital Anxiety and Depression Scale. The results demonstrated higher initial maternal anxiety scores in the burn, compared to the fracture and non ill/injured groups, which remained comparatively high 6 months later even though they decreased over time. Children with burn injuries, of the type included in this study, did not appear to develop significant psychological or behavioural sequelae. Following paediatric burn injury mothers appear to be at higher risk than children for developing psychological sequelae, which may have longer term implications for the child's outcome such as affecting compliance with treatment.

Acute Disease↗

PubMed2000

Chronic haematoma as a late complication of cosmetic breast augmentation.

To our knowledge, a chronic expanding haematoma has not been reported in a patient who received silicone gel breast prostheses for augmentation and never before at an interval as long as 12 years, as in our case. There have been occasional reports of chronic haematoma as complication of implantation of silicone breast prostheses after mastectomy for cancer, presenting 2.5-8 years later.

Journal Article↗

PubMed2000

Preventing the entrenchment of high expressed emotion in first episode psychosis: early developmental attachment pathways.

OBJECTIVE: As part of a strategy to consider the options for preventing the developmental entrenchment of expressed emotion (EE), we examine the early ontogeny of EE in a first-episode sample of individuals with psychosis and its links with the process of adaptation to change. METHODS: The key relatives of 50 first-episode psychosis patients from two locations were interviewed soon after patient referral and again 9 months later using measures of expressed emotion and loss. RESULTS: The developmental pathways of components of expressed emotion, particularly criticism and emotional over-involvement, were independent despite having a similar effect on outcome for patients. Initially, high levels of emotional over-involvement were reduced by follow up, with 37% resolving into high criticism. Overall expressed emotion status changed in 28.2% of key relatives (all parental), predominantly from high to low. High emotional over-involvement and low criticism are associated with significantly high levels of perceived loss in relatives. The metamorphosis of emotional over-involvement to criticism was linked to a reduction in perceived loss. CONCLUSIONS: Expressed emotion is not a stable index in relatives of first-episode psychosis samples. Appraisals of loss by relatives may be driving high emotional over-involvement with implications for family intervention programs. Attachment theory may help to explain some of the processes underlying resistance to change in some of the high-EE behaviours measured by expressed emotion.

Adolescent↗

PubMed2000

Cognitive therapy and recovery from acute psychosis: a controlled trial. 3. Five-year follow-up.

BACKGROUND: This paper describes the 5-year outcome of a cohort of patients who had received a cognitive therapy intervention during an acute episode of non-affective psychosis. METHOD: Thirty-four out of the original 40 patients who had taken part in a randomised controlled trial of a cognitive intervention were assessed, using standardised instruments completed at entry into the study. In the original trial, half the patients received a cognitive therapy programme (CT group) and the other half received recreational activities and support (ATY group). RESULTS: At follow-up no significant differences in relapse rate, positive symptoms or insight between the groups were found, although the CT group did show significantly greater perceived 'Control over illness' than the ATY group. For individuals who had experienced a maximum of one relapse in the follow-up period, self-reported residual delusional beliefs and observer-rated hallucinations and delusions were significantly less in the CT than in the ATY group. CONCLUSION: Cognitive therapy applied in the acute phase of a psychotic disorder can produce enduring and significant clinical benefits if experience of relapse can be minimised.

Acute Disease↗

PubMed1999

Mental health care for Asian, black and white patients with non-affective psychoses: pathways to the psychiatric hospital, in-patient and after-care.

BACKGROUND: This UK-based study compares the pathways to the psychiatric hospital and the provision of in-patient and after-care for Asian, black and white patients with non-affective psychoses. METHODS: Two overlapping samples of 120 patients, 40 from each ethnic group, were drawn; one on admission and the other at discharge. In addition to socio-demographic data, details were obtained on the pathways to care and the in-patient episode. An assessment of needs and service provision was undertaken 3 months post-discharge. Patient satisfaction was ascertained at each stage. RESULTS: Asian and especially black patients experienced more complex pathways and had higher levels of both involvement with the police and compulsory detention than their white counterparts. They were less likely to perceive themselves as having a psychiatric problem or as needing to go into hospital and expressed less satisfaction with the admission process. Black patients, as compared to Asian but especially white patients, were more often detained in hospital against their will, confined to the ward and treated within a secure environment. However, there were few differences in satisfaction with hospital care. Likewise, perceptions of unmet need, provision of after-care and satisfaction with services were similar across the ethnic groups. CONCLUSIONS: The implications of these findings are discussed. The potential of early intervention programmes and home treatment services to address the ethnic differentials identified in this study merit consideration.

Adolescent↗

PubMed1999

Mental health of elderly Asians in the UK.

Elderly Asians constitute a small proportion of the population compared to elderly whites [corrected], but this is growing rapidly. They share many of the disadvantages of the white elderly, as well as being non-white and alien. Many elderly Asians have now accepted that they will stay in the UK for good, which may contribute to increased stability in their mental health.

Aged↗

PubMed1998

Seasonal variations in hospital admissions for affective disorders by gender and ethnicity.

Hospital admission statistics for depression and mania have shown significant seasonal patterns. The present investigation was conducted to establish the pervasiveness of the impact of seasons on mood disorder presentation at Birmingham (52 degrees North) by gender and ethnicity. Non-mood disorder admissions were examined as a control to determine the specificity of any seasonal variation to affective illness. Case notes for 992 admissions, during January-December 1995 inclusive, to an inpatient unit were reviewed retrospectively. Admission data were broken down by gender and into three ethnic groups: Asian, white and black. Seasonality in admissions for depression, bipolar disorder and non-mood disorders was tested by gender and ethnicity. Admission frequencies for depression showed significant seasonal pattern, with the incidence of depression being highest in winter. Total admissions, bipolar and non-mood disorders did not show any significant seasonal variability. A gender effect was evident on seasonality of admissions for affective illness, with significant winter peak for depression and summer peak for bipolar disorder in women only. The Asian group was the only ethnic group that showed significant seasonal variation in depression, with a greater number of depressive episodes in winter. Environmental variables were related significantly to the incidence of mood disorders. Specific seasonal effect for affective illness was evidenced by the non-existence of seasonality in other psychiatric disorders. The reverse seasonal pattern for depression and mania suggests a maladaptive response of vulnerable individuals to specific functions of seasons.

Adult↗

PubMed1998

A mediational model of quality of life for individuals with severe mental health problems.

BACKGROUND: Despite the increasing importance of quality of life in the mental health field, the theoretical conceptualization of the construct remains poorly developed. A proposed mediational model of quality of life, which links subjective quality of life with self-related constructs, is examined with a group of long-term psychiatric hostel residents. The present study aims to develop a measure of quality of life based on the proposed model, to explore the data and their implications for service development and finally to conduct a preliminary analysis of the model's predictions. METHODS: A cross-sectional research design was employed. Quality of life interviews, using a modified version of Lehman's Quality of Life Interview, were carried out with 54 psychiatric residents in Greece. The model's predictions were examined by using a series of regression analyses. RESULTS: The results indicate that perceived improvements in lifestyle, greater autonomy and positive self-concept are significantly and directly associated with better quality of life. In contrast, a direct relationship between objective indicators and subjective quality of life was not found. CONCLUSIONS: The traditional two-part quality of life model that includes objective indicators of life circumstances and subjective indicators is extended to included the constructs of self-concept and perceived autonomy. The present extended mediational model of quality of life for individuals with long-term mental health problems appears to have important implications for the planning and delivery of mental health programmes.

Cross-Sectional Studies↗

PubMed1997

The role of nitric oxide in cancer. Improved methods for measurement of nitrite and nitrate by high-performance ion chromatography.

The short lifetime of nitric oxide (NO) in vivo impedes its quantitation directly; however, the determination of nitrite and nitrate ions as the end-products of NO oxidation has proven a more practical approach. High-performance ion chromatographic analysis of nitrite in biological fluids is hampered by the large amount of chloride ion (up to approximately 100 mmol/l) which results in insufficient peak resolution when utilizing conductimetric detection. Analysis of both anions in small sample volumes is also constrained by the need to minimise sample handling to avoid contamination by environmental nitrate. We report a means to remove Cl- ions from small sample volumes using Ag+ resin which facilitates quantitation of either nitrite and nitrate anions in biological samples, using silica or polymer based ion-exchange resins with conductimetric or electrochemical and spectrophotometric detection. Including a reversed-phase guard column before the anion-exchange guard and analytical column also greatly extends column lifetime.

Animals↗

PubMed1997

Seasonal changes in affective state in samples of Asian and white women.

Seasonality of the affective state has been reported to vary in direct proportion to latitude in temperate regions. The frequency of seasonal affective disorder (SAD) and the severity of the symptoms associated with it have been reported to be greater in higher than in lower latitudes. In addition, recent research has suggested a genetic loading for SAD. Most of the research on the seasonality of affect has been done in high latitude areas, seasonal mood cycles have been infrequently investigated in tropical areas, and no study has so far measured and compared seasonal changes in affect and behaviour in indigenous and populations non-indigenous to high latitudes. To rule out the biases associated with retrospective designs, a prospective longitudinal study was designed to investigate seasonal mood variations in indigenous white and non-indigenous Asian populations. Since previous research has indicated the excessive vulnerability of women to winter depression, it was decided to measure seasonality of the affective state only in women. To examine the relative effects of genetic predispositions and physical environment, the Asian group was further divided into "Asian" and "Asian-British". The former group comprised women who were living in England but who had been born and had spent considerably more time in their country of origin, while the latter group consisted of women who were born in England and who had lived there all their lives. The three groups of 25 women each were matched for age and socio-economic status, and were interviewed every month for 1 year using the Hospital Anxiety and Depression Scale (HAD), a Behavioural Change Inventory (BCI), the Ladder Scale of General Well-being (LSW) and a Monthly Stress Inventory (MSI). One retrospective scale was administered at the end of the study year to compare the extent of seasonal change in affect with that on the HAD-depression subscale. The results showed that seasonal depression peaked in winter in all three groups, with the incidence of winter depression being highest in the Asian group. Seasonal changes on several dimensions of behaviour were in the direction of winter depression for all three groups. States other than depression (anxiety and general well-being) did not show any seasonal variation. Hours of daylight was found to be the best predictor of seasonal variation in mood among environmental and psychosocial variables. There was no evidence to support a genetic hypothesis for SAD.

Adult↗

PubMed1997

Undetected gynaecological disorders in women with renal disease.

Women with chronic renal disease (CRD) who are on dialysis or have a functioning renal transplant are typically stoical in their attitude towards other health problems. We undertook a prospective study of 100 women with CRD to assess the prevalence of gynaecological disorders in this group of patients. Assessment included the measurement of follicle stimulating hormone, luteinizing hormone, prolactin and oestradiol concentrations, cervical cytology and a pelvic ultrasound scan. We found that gynaecological problems are highly prevalent and frequently unrecognized. Of these women, 58% had a menstrual disorder, with uncontrolled menorrhagia being a significant problem when it aggravated the chronic anaemia of renal disease, and 35% were menopausal, including seven women under the age of 40 years. Menopausal symptoms were undertreated. We identified a 14-fold increase in premature ovarian failure secondary to CRD and the use of cyclophosphamide therapy. In all, 22% of the women were subfertile and 10% had an abnormal smear, with cervical dyskariosis being significantly increased because of long-term immunosuppression. Contraceptive advice had often been absent or inappropriate. We conclude that formal gynaecological review should be routinely available for women with CRD.

Adolescent↗

PubMed1996

Elevation of intracellular cyclic AMP induces an anergic-like state in Th1 clones.

Because elevated intracellular cAMP suppresses T cell receptor (TCR)-mediated effector activity and/or proliferation in response to antigen but does not always affect IL-2-stimulated proliferation, the effects of cAMP on a T lymphocyte response to antigen resemble antigen-induced anergy. To test the hypothesis that elevated cAMP induces anergy in T lymphocytes, we have precultured murine Th1 clones responsive to porcine myelin basic protein (PMBP) with dibutyryl cyclic AMP (dbcAMP) or forskolin and subsequently removed the dbcAMP or forskolin and measured the proliferative response of the clones to antigen and antigen-presenting cells (APC) in the presence or absence of exogenously added interleukin-2 (IL-2). Cells precultured with dbcAMP or forskolin for 3 days did not proliferate or produce IL-2 in response to antigen and APC, but did proliferate to antigen and APC in the presence of IL-2. Cells that had not been stimulated recently with antigen/APC or IL-2 were not affected by dbcAMP, while cells stimulated recently with antigen/APC and IL-2 were susceptible to the anergizing effect of dbcAMP. These observations support the hypothesis that elevation in intracellular cAMP in antigen-activated Th1 clones, prior to subsequent culture with antigen, induces a state of anergy.

Animals↗

PubMed1996

Seasonal changes in affective state measured prospectively and retrospectively.

BACKGROUND: The study was designed to investigate whether seasonal mood and behavioural changes are detectable prospectively in a non-clinical population in the way they have been reported in retrospective studies. The specificity of any seasonal fluctuation in affective state was also investigated by measuring anxiety as well as depression. METHOD: To measure seasonal fluctuations in affect and behaviour prospectively, 25 women were interviewed every month for one year using four scales (depression, anxiety, stress, and behavioural change). Retrospective accounts of mood and behaviour at the end of the year were collected with the Seasonal Pattern and Assessment Questionnaire (SPAQ). RESULTS: Seasonal depression peaked in winter as did atypical behaviour when measured either prospectively or retrospectively, but the difference between winter and summer was much more pronounced in the retrospective data. No seasonal effect was found for anxiety or psychosocial stressors. CONCLUSIONS: The results obtained by retrospective techniques have limited reliability. In the future, more prospective studies with unbiased, standardised instruments are recommended to measure seasonal variations in affect and behaviour.

Adult↗

PubMed1996

Cognitive therapy and recovery from acute psychosis: a controlled trial. I. Impact on psychotic symptoms.

BACKGROUND: The application of cognitive therapy (CT) to psychosis is currently being developed in the UK. This paper reports a trial of CT in acute psychosis with the objective of hastening the resolution of positive symptoms and reducing residual symptoms. METHOD: Of 117 patients with acute non-affective psychosis, 69 satisfied inclusion criteria and 40 proceeded to stratified randomisation. The experimental intervention involving individual and group CT was compared with a group receiving matched hours of therapist input providing structured activities and informal support; routine pharmacotherapy was provided by clinicians blind to group allocation. Patients were monitored weekly using self-report and mental state assessments during admission and over the subsequent nine months. RESULTS: Both groups showed a decline in positive symptoms but this was more marked in the CT group (P < 0.001). At 9 months 5% of the CT group, v.56% of the control group, showed moderate or severe residual symptoms. CONCLUSION: CT appears to be a potent adjunct to pharmacotherapy and standard care for acute psychosis. Issues concerning internal and external validity of the study and opportunities for further research are discussed.

Acute Disease↗

PubMed1996

Cognitive therapy and recovery from acute psychosis: a controlled trial. II. Impact on recovery time.

BACKGROUND: A trial of CT in acute psychosis conducted by the authors has shown a significant impact on the rate and degree of recovery of positive symptoms, the focus of the intervention. This paper seeks to determine whether these effects generalise to other features of acute psychosis including dysphoria, insight and "low level' psychotic thinking which were not directly targeted. METHOD: Measures of dysphoria, insight and psychotic thinking were taken over a six-month period following presentation for acute psychosis. Using survival analysis, time to recovery from psychosis using three definitions of increasing stringency was compared between the CT and control group. RESULTS: CT was associated with a 25-50% reduction in recovery time depending on the definition used. CONCLUSION: The impact of the CT intervention extended beyond positive symptoms to include insight, dysphoria and "low level' psychotic thinking. Nevertheless this kind of "clinical' recovery required a median of 20 weeks to complete. Implications for clinical models of acute care are discussed.

Acute Disease↗