TSC-22D1 isoforms have opposing roles in mammary epithelial cell survival.

Transforming growth factor beta (TGFbeta)-stimulated clone-22 domain family member 1 (TSC-22D1) has previously been associated with enhanced apoptosis in several cell systems. In an attempt to identify novel factors that are involved in the control of cell death during mammary gland involution, we found that the mRNA for isoform 2 of TSC-22D1 was highly upregulated 24 h after forced weaning, when a dramatic increase in cell death occurred, closely following the expression of the known inducer of cell death during involution, TGFbeta3. This was paralleled by strongly increased TSC-22D1 isoform 2 protein levels in the luminal epithelium. In contrast, RNA and protein expression levels of the isoform 1 of TSC-22D1 did not change during development. Whereas isoform 2 induced cell death, isoform 1 suppressed TGFbeta-induced cell death and enhanced proliferation in mammary epithelial cell lines. Furthermore, four distinct forms of isoform 2 protein were detected in the mammary gland, of which only a 15-kDa form was associated with early involution. Our data describe novel opposing functions of the two mammalian TSC-22D1 isoforms in cell survival and proliferation, and establish the TSC-22D1 isoform 2 as a potential regulator of cell death during mammary gland involution.

Self-medication of antibacterials without prescription (also called 'over-the-counter' use). A report of a Working Party of the British Society for Antimicrobial Chemotherapy.

The availability of antimicrobial agents for self-medication may increase and could include antibacterial agents for oral or topical use. Wholesale deregulation of antibacterials would be undesirable and likely to encourage misuse of classes of agents currently important in the management of serious infections. Changed regulation from Prescription-Only Medicine (POM) to Pharmacy (P) medicine of selected agents with indications for short-term use in specific minor infections and illness is likely to have advantages to the user. However, safeguards to their use would need to be included in the Patient Information Leaflet (PIL). Agents and indications for self-medication are discussed. Any alteration in licensed status from POM to P will require careful risk-benefit assessment, including the likely impact on bacterial resistance. Safety issues also include concerns relating to age of the user, pregnancy, underlying disease and the potential for drug interactions. The importance of appropriate information with the PIL is emphasized, as is the role of the pharmacist, while ways of improving adverse event notification and monitoring are discussed. The paucity of good denominator-controlled data on the prevalence of in-vitro resistance is highlighted, and recommendations for improving the situation are made. There are currently no levels of resistance accepted by regulatory bodies on which to base a licensing decision, be it for granting a product licence, renewal of a licence or a change in licensed status from POM to P. Due consideration should be given to: the validation of user-defined indications in comparison with those medically defined; the enhancement of pharmacy advice in the purchase of such agents; improved safety monitoring; the establishment of systematic surveillance of susceptibility data.

Management of hypertension in patients developing end-stage renal failure.

The benefits of treating hypertension include preventing or delaying the progression of chronic renal failure, and reducing the cardiovascular complications of patients with renal disease. We examined how well hypertension had been managed in all 145 patients from a single health district who started dialysis during a 3-year period. Data relating to management of hypertension, including all blood pressure readings, were obtained from their general practice and hospital case notes. The anonymized data were reviewed by two independent assessors against a set of standards based on the British Hypertension Society guidelines. There was close agreement between the assessors. Complete records were obtained in 98.5% of cases. Of the 145 patients, 107 (76.4%) were hypertensive before developing end-stage renal failure. There were departures from standards in all categories of care: 24.3% in detection/diagnosis, 29% in investigation, 22.4% in referring to a nephrologist, and 17% in follow-up. The British Hypertension Society recommended standard for diastolic blood pressure of 90 mmHg was achieved in only 45%. In 32%, the assessors independently concluded that poor blood pressure control might have affected adversely the progression of renal failure. New methods of dealing with these problems are required and possible approaches are discussed.

Generating social class data in primary care.

The objective of this study was to compare three methods of collecting social class data in general practice. The setting was a rural dispensing practice on the Nottinghamshire/Lincolnshire border. The methods examined were: (a) a self-administered questionnaire to 200 patients to determine their social class based on the occupation of the head of household; (b) members of the practice staff were asked to assign a social class to these households based on their local knowledge; and (c) use of small area statistics from the 1991 census data using modal and weighted methods. It was found that the practice staff were unable reliably to assign a social class to the households. The modal method of using small area statistics to assign social class to households through their postcode and its link to the census data was also inaccurate. While a personal questionnaire will remain the only method for assigning a social class to individual patients for clinical care or most research, the weighted method of small area statistics is shown to be a cost-effective and sufficiently accurate method for health needs assessment in general practice.

Prescribing costs in dispensing practices.

OBJECTIVE: To examine differences in prescribing between dispensing and non-dispensing practices. SETTING: The 108 practices covered by Lincolnshire Family Health Services Authority. DESIGN: Analysis of prescribing data for 1990-1 from PD2 reports from the Prescription Pricing Authority in relation to data on practice characteristics obtained from Lincolnshire Family Health Services Authority; and aggregated level 3 prescribing and cost information (PACT data) for 10 selected drugs from the Prescription Pricing Authority to examine amounts prescribed. MAIN OUTCOME MEASURES: Prescribing cost per patient, items per patient, and cost per item in dispensing and non-dispensing practices. RESULTS: Dispensing practices had higher prescribing costs per patient than non-dispensing practices. This difference held for non-dispensing patients within dispensing practices. Structural features failed to explain the differences in prescribing cost, except for the higher numbers of elderly patients in dispensing practices (which explained 13% of the difference) and the number of partners (5%). The main determinant of the difference was the lower use of generic drugs in dispensing practices (84%). Dispensing patients were prescribed lower quantities of drugs on average for each item. CONCLUSIONS: Dispensing practices could reduce their prescribing expenditure to that of non-dispensing practices by increasing their prescribing of generic drugs. The shorter prescribing intervals for dispensing patients may be due to dispensing fees being related to the number of prescribed items.

Referral letters and replies from orthopaedic departments: opportunities missed.

OBJECTIVE: To study delays between sending referral letters and the outpatient appointment and to assess the content of referral and reply letters, their educational value, and the extent to which questions asked are answered by reply letters. DESIGN: Retrospective review of referrals to 16 consultant orthopaedic surgeons at five hospitals, comprising 288 referral letters with corresponding replies, by scoring contents of letters. SETTING: Orthopaedic teaching hospitals in Nottingham, Derby, and Mansfield. MAIN OUTCOME MEASURES: Weighted scores of contents of referral and reply letters, assessment of their educational value, and responses to questions in referral letters. RESULTS: Median outpatient delay was 23.4 weeks. There was no significant decrease in waiting time if the referral letter was marked "urgent" but a significantly greater delay (p less than 0.01) if referrals were directed to an unnamed consultant. The content score was generally unsatisfactory for both referrals and replies, and there was no correlation for the content scores of the referral letter and its reply (r = 0.13). Items of education were rare in the referral letters (8/288; 3%) and significantly more common in replies (75/288; 26%) (p much less than 0.001). Senior registrars were significantly more likely to attempt education than other writers (p less than 0.02). Education in replies was significantly related to increased length of the letter (p less than 0.05) and was more likely to occur if the referral was addressed to a named consultant (p less than 0.03). 48 (17%) Referral letters asked questions, of which 21 (44%) received a reply. No factor was found to influence the asking of or replying to questions. CONCLUSIONS: The potential for useful communication in the referral letter and in the reply from orthopaedic surgeons is being missed at a number of levels. The content is often poor, the level of mutual education is low, and the use of the referral letter to determine urgency is deficient. Most questions asked by general practitioners are not answered.