Randomised controlled trial of combined diphtheria, tetanus, whole-cell pertussis vaccine administered in the same syringe and separately with Haemophilus influenzae type b vaccine at two, three and four months of age.

An open randomised controlled multicentre study compared the immunogenicity and reactogenicity of three vaccines given by injection at two, three and four months of age. Children (89) received Haemophilus influenzae type b (Hib) vaccine (SmithKline Beecham Biologicals [SB]) administered in the same syringe with combined diphtheria-tetanus-whole-cell pertussis (DTPw) vaccine (Evans); 75 received Hib vaccine (SB) administered as a separate injection with DTPw vaccine; 66 received Hib vaccine (Pasteur Merieux [PM]) administered as a separate injection with DTPw vaccine. All subjects in both groups receiving Hib (SB) vaccine had levels of antibodies to the Hib polysaccharide polyribosylribitol phosphate (PRP) greater than 0.15 microgram ml-1 as did 97% of those receiving Hib (PM) vaccine 1 month after administration of the final vaccine dose. Subjects in all three groups demonstrated an immunological response to pertussis, diphtheria and tetanus antigens. The geometric mean titres of the group given Hib (SB) and DTPw vaccine mixed in the same syringe were lower than the other groups. There were no apparent differences between the treatment groups in the incidence of local or systemic reactions, or serious adverse events. This study has confirmed that it is possible to halve the number of injections necessary to offer protection, with advantages to parents, children, doctors and nurses, using a combined DTPwHib vaccine and in accordance with the UK's accelerated primary immunisation schedule at two, three and four months of age.

Obtaining the views of general practitioners on the services to which they refer patients--a locality approach.

A survey, with a locality emphasis, of the opinions of Fife general practitioners (GPs) on the quality and availability of a selection of services to which the GPs refer their patients was undertaken. Far more GPs rated services as 'poor' for availability than for quality. GPs acting as locality advisers were actively involved in the planning and execution of the survey as well as the dissemination of the results. The overall response rate was disappointing considering this approach.

Effects of fine needle aspiration on subsequent mammograms.

The effects of fine needle aspiration on subsequent mammography were studied in a group of women who were referred with palpable breast lumps. Fifty-two women aged between 36 and 73 (median 53) years underwent mammography before and within 5 days of needle aspiration. Preaspiration and postaspiration mammograms were examined 'blind' by one radiologist. In ten cases, a difference was seen between the preaspiration and postaspiration films. In seven (aged 36-50 years) this was due to aspirated cysts. In three the differences were unexpected and were more significant, although the radiological diagnosis was not altered. If this proportion is extrapolated for a large number of patients then significant numbers of artifacts from fine needle aspiration might be seen on mammograms. It is possible that some might be interpreted falsely as malignant and some small cancers might be obscured. Women accepted mammography more readily before aspiration than after.

Tamoxifen metabolism is altered by simultaneous administration of medroxyprogesterone acetate in breast cancer patients.

We have measured the levels of tamoxifen and three of its metabolites in the blood of patients receiving tamoxifen alone or combination therapy with tamoxifen and medroxyprogesterone acetate. Our results indicate that addition of the progestogen significantly alters the metabolism of tamoxifen over a six-month period. We suggest that the interaction between these drugs may involve additional sites (probably hepatic) besides the desired target tumour.

Pyridinium crosslinks as markers of bone resorption in patients with breast cancer.

Collagen breakdown, and thus bone resorption, can now be assessed by measuring the urinary excretion of the collagen crosslinks, pyridinoline (Pyd) and deoxypyridinoline (Dpd). In a pilot study we measured Pyd and Dpd in 20 patients with breast cancer, ten with known bone metastases and ten with no recognised metastases in bone or elsewhere after 1 year's subsequent follow up. Eight out of the ten patients with metastases had crosslink excretion values higher than the reference interval, but so did some patients without known metastatic disease. For both crosslinks there was a clear correlation with serum alkaline phosphatase activity measured at about the same time. We consider that measurement of urinary collagen crosslink assays may have a place in the early detection of metastatic spread to bone.

Potential use of tumour marker CA 15-3 in the staging and prognosis of patients with breast cancer.

The tumour marker CA 15-3 has been assayed in 130 patients with breast cancer and correlated with stage of their disease at presentation. The median value of CA 15-3 (43 kU/l) in 26 patients with stage IV disease was significantly higher than the median for 97 patients classified as stage I or II (17 kU/l). Values were elevated in 18 of 21 (86%) patients with bone metastases at presentation. For the 41 patients with stage I or II disease presenting with levels of CA 15-3 of greater than 20 kU/l, the disease-free interval and survival were significantly less than for 56 patients presenting with levels of less than 20 kU/l. CA 15-3 provides additional information to conventional staging tests for patients presenting with breast cancer and may also have a role as a prognostic indicator. This may be particularly useful in the selection of patients for neoadjuvant therapy.

Patterns of presentation of breast disease over ten years in a specialised clinic.

A clinic specialising in breast disease has been surveyed over a decade. Detailed information has been collected on 3,500 women with benign breast disorders and 950 with breast cancer. Over this time, the demand for and utilisation of this facility has increased steadily. Over the ten years, there has been a trend for a higher proportion of breast cancers to be smaller in size and for fewer cancers to be locally advanced or metastatic at presentation. Critical appraisal of referral and consultation patterns indicates that the original aims of establishing this clinic have not been maintained. Paradoxically, this is a result of the success of the exercise. Measures which might lead to a higher proportion of patients with breast cancer being managed at the Breast Clinic rather than a General Surgical Outpatient Clinic are discussed.

Long-term follow-up of elderly patients with locoregional breast cancer treated with tamoxifen only.

One hundred and thirteen women aged 70 years or more with locoregional breast cancer were treated with tamoxifen alone as primary treatment. They were followed for a minimum of 5 years. Complete response occurred in 38 women, partial response in 17, no change in 34 and progressive disease in 24. Where progressive disease occurred, or where patients relapsed after an initial response, the most suitable conventional therapy was given. The actuarial 5-year survival rate was 49.4 per cent for all patients and was much higher (92 per cent) in those showing an initial complete response. Seventy patients (61.9 per cent) were not controlled by tamoxifen alone to death or most recent follow-up. Tamoxifen provides an alternative treatment for operable breast cancer in older women in the short term and may be particularly suitable for those with concurrent disease or who are unwilling to undergo surgery. The low morbidity rate from tamoxifen must be balanced against the need to maintain close follow-up. In the medium to long term, sole primary treatment by tamoxifen delays more definitive therapy.

Meakin adjuvant regimen in premenopausal patients with breast cancer.

A 10-year experience using ovarian ablation and prednisolone as adjuvant therapy for premenopausal patients with breast carcinoma, emphasizing tolerability and morbidity is reported. Thirty patients (15 aged less than 45 years, 15 aged greater than or equal to 45 years; range 28-54 years) underwent mastectomy/lumpectomy with axillary clearance (with or without local irradiation) followed by ovarian irradiation and prednisolone therapy (2.5 mg three times daily for 5 years). Patients were reviewed every 3 months for the first 3 years and every 6 months thereafter. Follow-up was between 1.5 and 10 years (median 5 years). Twenty-four patients are still alive. Three patients stopped therapy because of side-effects. There was a mean(s.e.m.) weight gain of 8.46(1.69) per cent on therapy. Nineteen patients have been weaned off prednisolone over a period of 0.5-7.5 months (median 2 months) and the median length of time off steroids is now 3 years (range 0.5-5 years). This regimen appears to be associated with an acceptable level of patient tolerability and a low chronic morbidity rate and should be considered as an alternative to adjuvant systemic cytotoxic therapy.

A randomised controlled trial of medroxyprogesterone acetate in mastalgia.

A double-blind crossover study giving 20 mg/day of medroxyprogesterone acetate during the luteal phase was carried out in 26 women with cyclical mastalgia. Symptomatic response to this progestogen supplementation or placebo was assessed objectively by clinical examination and subjectively by linear analogue scales and breast pain charts. No significant relief of pain or tenderness was found on placebo or active treatment, irrespective of treatment order, and breast nodularity was similarly unaltered. No evidence of progesterone deficiency or prolactin abnormality was found. Side-effects were incurred in 11 patients (five on placebo, five on active treatment and one while on both) and were mostly vague premenstrual symptoms. We conclude that the therapeutic response of medroxyprogesterone acetate in cyclical mastalgia is no better than placebo and that progestogen supplementation can no longer be recommended for routine use in the management of breast pain.