The use of appetite suppressants, a putative inverse marker of prescribing quality, was analysed in the former Northern Regional Health Authority (RHA) and in England using National Health Service prescribing data and sales and patient-linked prescribing data supplied by Intercontinental Medical Statistics (IMS). The number (in thousands) of National Health Service prescriptions for appetite suppressants dispensed fell from 393 in 1991 to 235 in 1994. Per capita prescribing frequency varied threefold between different RHA and between individual Family Health Service Authorities (FHSA) within the former Northern RHA (NRHA). Prescribing frequency was higher in the spring and summer quarters and reduced in the winter quarter. Of 532 general practices in the NRHA, 82 (15%) prescribed no appetite suppressants between April 1993 and March 1994, while 70 (13%) prescribed more than 500 defined daily doses (DDDs) per 1000 patients, accounting for 47% of all prescribing. Only 53% of pharmacy purchases of appetite suppressants were accounted for by NHS prescribing and as little as 21% for phentermine, indicating substantial prescribing outwith the NHS. In 1991, 73,759 DDDs were supplied to pharmacies each day, the majority being diethylpropion (31,226) and phentermine (24,349). The fall in NHS prescribing is welcome as these drugs are of dubious clinical value and may be associated with serious adverse effects. Because of substantial non-NHS prescribing, routinely available prescribing data does not accurately quantify total prescribing of these agents.

Journal Article↗

PubMed1996

The treatment of common mental disorders by a community team based in primary care: a cost-effectiveness study.

Thirty patients suffering from new episodes of depression or anxiety disorders seen by a hospital-based psychiatric service were matched for severity of illness with 30 patients seen by a community mental health team based upon primary care. These patients were drawn from a total of 108 such patients seen in the community and 57 seen by the hospital service. Clinical and social outcomes were similar in both groups, and neither was clearly superior in terms of quality of clinical information recorded. However, patients treated in the community were seen more quickly, had more continuity of care and were more satisfied with the service. Health services costs were less for those patients treated in the community, because patients were less likely to be admitted. With one atypical patient excluded, treatment by the community team is more cost effective. The greater number of patients seen by the primary-care-based service means that there is no overall cost saving to the NHS.

Adolescent↗

PubMed1996

Apparent bypass of negative selection in CD8+ tumours in CD2-myc transgenic mice.

A role for antigen stimulation in lymphoid neoplasia has been postulated and is supported by indirect evidence that suggests that the interaction of antigen with both T cells and B cells may constitute an epigenetic event that can contribute to tumour induction or tumour progression. Using myc-bearing transgenic mice that develop mainly clonal T-cell lymphomas we have investigated the possibility that endogenous antigen-mediated clonal deletion might be overridden in tumorigenesis. CD2-myc transgenic mice were backcrossed on to a CBA/Ca background to ensure Mtv-mediated deletion of V beta 11-expressing T cells in the resultant offspring. Lymphomas arising from these mice were subsequently screened for V beta 11 expression. There was a clear correlation between the age at which mice developed neoplasia and the tumour phenotype. Mice with CD4- CD8+ tumours succumbed to thymic lymphoma at a significantly younger age than mice developing CD4+ CD8+ tumours. A small number of tumours consisted of the 'forbidden' V beta 11 phenotype, showing that cells vulnerable to transformation could escape negative selection. The majority of the V beta 11-positive tumours were CD4- CD8+ and were only observed in mice showing clinical evidence of tumour development at a relatively young age. The phenotype of these cells and the age at which tumours arose suggests that T cells escaping tolerance may be susceptible to transformation.

Animals↗

PubMed1996

Adhesion molecule interactions in human glomerulonephritis: importance of the tubulointerstitium.

Infiltration of leukocytes into glomerular and interstitial regions of the kidney is a key event in the pathogenesis of human glomerulonephritis. This process is mediated by specific adhesion molecules, some of which are expressed in a coordinated fashion following endothelial cell activation. We have assessed the pattern of expression of the selectins (E, P and L), and the counter-receptors (LFA-1 and ICAM-1, and VLA-4 and VCAM-1 in 119 renal biopsies using sequential sections, and have correlated this with the degree of histological damage (tubular atrophy and interstitial fibrosis) and the intensity of the macrophage infiltrate. Sections were stained with the monoclonal antibodies using a standard alkaline phosphatase anti-alkaline phosphatase (APAAP) technique. There were strong correlations between the following: (1) expression of LFA-1, VLA-4, and L-selectin in the periglomerular region, interstitium and in focal interstitial infiltrates and the presence of macrophages in these regions; (2) de novo tubular expression of ICAM-1 and VCAM-1; (3) staining for ICAM-1 and VCAM-1 on focal cellular infiltrates within the interstitium; and (4) staining for E- and P-selectin on extraglomerular endothelium. These are also strongly correlated with the degree of chronic histological damage. There was, however, no correlation between glomerular expression of adhesion molecules or glomerular macrophage infiltration and chronic histological damage. Although expression of VCAM-1 by the glomerular mesangium was strongly correlated with the presence of cells staining for VLA-4 within the glomerulus, glomerular expression of adhesion molecules correlated poorly with their expression in other sites. These results show that coordinated up-regulation of adhesion molecule expression in the tubulointerstitium is associated with interstitial fibrosis and tubular atrophy and may contribute, therefore, to the progression of renal disease.

Biopsy↗

PubMed1996

Discordant clinical presentation and outcome in infant twins sharing a common clonal leukaemia.

We report the different presentation features and clinical outcome between two identical infant twins with acute lymphoblastic leukaemia with a shared clonal disease and MLL gene rearrangement. One twin relapsed and died, but the other is in complete remission > 4 years after diagnosis. These data, and similar observations on other twin infants with leukaemia, suggest that despite a common clonal in utero, post-natally these leukaemias can evolve independently, at different rates, in the twinned individuals, and that the usually fatal leukaemia associated with t(4;11) MLL gene rearrangement can be effectively treated when the leukaemic burden is small.

Bone Marrow↗