Comparing the effectiveness of imagery focussed cognitive therapy to group psychoeducation for patients with bipolar disorder: A randomised trial.

BACKGROUND: Bipolar disorder is a severe, chronic mental disorder. Treatment options are limited, with pharmacological approaches continuing to dominate. However, relapse rates remain high. Several adjunctive psychosocial interventions, mostly psychoeducation (PE) and cognitive behavioural therapy (CBT), have been trialled, but treatment innovation is still needed. In the past, brief group PE has proven as beneficial as longer individual CBT in reducing levels of depression and increasing self-management strategies. We compared the relative effectiveness of group PE to an imagery focussed cognitive behavioural therapy (ImCT). STUDY DESIGN: This was a randomised parallel group study with both daily and weekly measures. A total of 62 adult patients were randomly allocated to either ImCT or group PE. Daily, weekly and pre-and post-intervention measures were used to assess impact on (i) mood instability, (ii) overall levels of depression, anxiety and mania, and (iii) general functioning, hopelessness and imagery characteristics. A four-week baseline and 16-week follow-up period were included. RESULTS: Mood instability reduced in both conditions after intervention. Levels of mania, depression and anxiety also reduced in both conditions, but on the daily measures, depression and anxiety significantly more so in the ImCT condition. Compared with the PE condition, the ImCT condition additionally showed increased level of functioning, reduced hopelessness, and a decrease in intrusive, problematic imagery. LIMITATIONS: These findings need to be replicated in a larger trial. CONCLUSIONS: Findings suggest that ImCT is a promising new avenue for management of bipolar disorder, an area in which treatment development is urgently needed.

Applications of time-series analysis to mood fluctuations in bipolar disorder to promote treatment innovation: a case series.

Treatment innovation for bipolar disorder has been hampered by a lack of techniques to capture a hallmark symptom: ongoing mood instability. Mood swings persist during remission from acute mood episodes and impair daily functioning. The last significant treatment advance remains Lithium (in the 1970s), which aids only the minority of patients. There is no accepted way to establish proof of concept for a new mood-stabilizing treatment. We suggest that combining insights from mood measurement with applied mathematics may provide a step change: repeated daily mood measurement (depression) over a short time frame (1 month) can create individual bipolar mood instability profiles. A time-series approach allows comparison of mood instability pre- and post-treatment. We test a new imagery-focused cognitive therapy treatment approach (MAPP; Mood Action Psychology Programme) targeting a driver of mood instability, and apply these measurement methods in a non-concurrent multiple baseline design case series of 14 patients with bipolar disorder. Weekly mood monitoring and treatment target data improved for the whole sample combined. Time-series analyses of daily mood data, sampled remotely (mobile phone/Internet) for 28 days pre- and post-treatment, demonstrated improvements in individuals' mood stability for 11 of 14 patients. Thus the findings offer preliminary support for a new imagery-focused treatment approach. They also indicate a step in treatment innovation without the requirement for trials in illness episodes or relapse prevention. Importantly, daily measurement offers a description of mood instability at the individual patient level in a clinically meaningful time frame. This costly, chronic and disabling mental illness demands innovation in both treatment approaches (whether pharmacological or psychological) and measurement tool: this work indicates that daily measurements can be used to detect improvement in individual mood stability for treatment innovation (MAPP).

The association between cell proliferation and apoptosis: studies using the cell cycle-associated proteins Ki67 and DNA polymerase alpha.

The process of apoptosis is associated with the inappropriate expression of cell cycle regulatory proteins, which has led to the proposal that the apoptotic pathway represents an abortive attempt to pass through the cell proliferation cycle. To investigate this hypothesis, we examined the expression of two proliferation-associated antigens in apoptotic cells. Apoptotic bodies seen in a range of normal and pathological tissues are often positive for the Ki67 antigen, indicating that these cells were in the cell cycle during the period that they died. In contrast, spontaneous apoptosis of human polymorphonuclear leukocytes maintained in culture was not associated with the expression of either Ki67 or DNA polymerase a. In addition, apoptotic bodies in the pre-menstrual endometrium did not express the Ki67 antigen. These results indicate that, contrary to previous suggestions, apoptosis does not always depend on cell cycle entry. The use of antibodies to Ki67 should be valuable in defining the association of apoptosis with proliferation in a wide range of cells and tissues.

Identification of the origin of cells in human basal cell carcinoma xenografts in mice using in situ hybridization.

In an attempt to identify more clearly the origin of cells in human basal cell carcinoma xenografts in mice, paraffin and frozen sections were subjected to in situ DNA hybridization with biotin labelled human and murine DNA probes. Human skin and mouse skin sections were used as controls. As expected, the implanted epithelium reacted with the human DNA probe and the surface epithelium and most of the stromal cells reacted with the murine probe. However, the stroma immediately surrounding the implanted epithelium contained cells of human origin mixed with murine cells. Occasional murine cells (presumed inflammatory) were present in the human implanted epithelium. Assessment showed no correlation between the degree of differentiation of the implanted epithelium and the ratio of human/murine cells in the contiguous stroma. This technique provides a sensitive test for identifying human cells in xenografts and may be useful in assessing the role of stromal cells in the differentiation of a variety of carcinomas.

The Value of Immunocytochemistry in Differentiating High-Grade: Lymphoma from Other Anaplastic Tumours: A study of anaplastic tumours from 1940 to 1960.

Immunocytochemistry is now established in many histology laboratories for diagnostic purposes and is routinely used in ascribing an origin to poorly differentiated tumours. This raises the question of whether traditional morphological skills are being abandoned in favour of new technology and, if so, whether that is justified. Twenty-three lymph node biopsies diagnosed as anaplastic carcinoma, reticulosarcoma or unclassifiable tumour between 1940 and 1960 (when immunocytochemistry was not available) were retrieved from the archives of the Radcliffe Infirmary. Paraffin sections were stained with a panel of monoclonal antibodies previously shown to be useful in the identification of tumours of uncertain origin. Of the 15 cases given a definite morphological diagnosis six (40%) were shown to be incorrect on the basis of immunostaining. In the eight remaining cases in which no diagnosis was recorded immunostaining provided a clear diagnosis in seven instances. These results are similar to those recorded on contemporary cases and demonstrate the value of immunocytochemical staining, as an adjunct to traditional morphological examination. In addition, it is clear that currently available monoclonal antibodies are suitable for use on routinely processed material more than 30 years old.

Giant cell myocarditis associated with lymphoma: an immunocytochemical study.

A case of giant cell myocarditis in a patient with non-Hodgkin's lymphoma is reported. To our knowledge, this is a previously unrecorded association and supports the hypothesis that the aetiology of giant cell myocarditis is related to a changed immune state. Immunohistochemical investigation of this case with a panel of monoclonal antibodies against a range of leucocyte and muscle antigens supports the view that the giant cells have a histiocytic rather than a myogenic origin.