New roles and relationships in the NHS--barriers to change.

The incoming Labour Government's vision for reforming the NHS in Scotland was outlined in the White Paper Designed to Care. While bearing similarities to the proposals outlined for the rest of the UK, it also had distinctive differences. Organisational structures, roles, and relationships between the different parts of the NHS were to be fundamentally altered, particularly in primary and community care. This paper reports upon a series of interviews undertaken across several Health Board areas, with key stakeholders involved in the primary and community sectors. These interviews were intended to examine the development and evolution of the new organisational arrangements, and to identify potential barriers to the successful implementation of Designed to Care. Several barriers and sources of institutional resistance to the new roles and relationships were found during this study, and are discussed. Suggestions upon how these may be overcome and implementation improved are then made.

Effect of temperature and the role of testicular descent on post-natal testicular androgen production in the mouse.

Testes from mice aged 3, 15, 25, 30 or 60 days were incubated under basal conditions or in the presence of hCG. One testis from each animal was incubated at 37 degrees C while the contralateral testis was incubated at 32 or 34 degrees C. During development total androgen production in response to hCG (at 32 degrees C) showed a marked increase between 15 and 30 days. The major androgens secreted at this time were testosterone and 5 alpha-androstane-3 alpha,17 beta-diol. There was little change in total androgen production between 30 and 60 days but by 60 days testosterone was the dominant androgen. Both basal and hCG-stimulated androgen production were temperature sensitive. These effects were most pronounced at 30 and 60 days with androgen production significantly inhibited at 37 degrees C. To examine the role of testicular descent in regulating steroidogenesis animals were rendered unilaterally cryptorchid at 19 days of age. At 25 days, when descent is normally completed in the mouse, there was no significant difference in steroidogenesis between scrotal and abdominal testes. By 30 days, however, the steroidogenic potential of the abdominal testis was significantly lower than that of the scrotal testis. These results show that testicular steroidogenesis is sensitive to temperature changes around the time of testicular descent, although descent itself is not required to achieve an adult level of steroidogenesis. The results also show, however, that testicular descent is required to maintain the adult level of steroidogenesis.

Effect of testosterone on testicular steroidogenesis in the hypogonadal (hpg) mouse.

Previous studies have shown that androgens have direct inhibitory effects on steroidogenesis in active Leydig cells. It is not clear what effect androgens have on inactive Leydig cell either through direct action on the cell itself or indirectly through stimulation of Sertoli cell activity. The hpg mouse has undetectable levels of circulating gonadotrophins and the gonads fail to develop post-natally. The effect of androgen treatment on testicular steroidogenesis and morphology was examined in these animals. Treatment with testosterone propionate for two weeks significantly increased testicular and seminal vesicle weight. Seminiferous tubules showed marked development in androgen-treated animals, indicating increased Sertoli cell activity, but the abnormal Leydig cell morphology of the hpg testis was unchanged. Androgen production per testis in vitro was low in control hpg animals and remained unaffected by treatment with androgen. Similarly, the pattern of [3H]pregnenolone metabolism was not significantly affected by androgen treatment. The androgen content of the testis was higher in androgen-treated animals but this could be accounted for by uptake of administered steroid from the circulation. It is concluded that androgens have no direct trophic effect on Leydig cells and that stimulation of Sertoli cell activity is not, in itself, sufficient to affect Leydig cell function.

Effect of LH injections on testicular steroidogenesis, cholesterol side-chain cleavage P450 mRNA content and Leydig cell morphology in hypogonadal mice.

Hypogonadal (hpg) mice have a congenital deficiency of hypothalamic gonadotrophin-releasing hormone (GnRH) and the gonads consequently lack exposure to gonadotrophins during development. We injected male hpg mice with LH for 10 days to investigate whether LH alone can stimulate normal steroidogenesis in these animals. Control animals had an inactive interstitium and very few germ cells. Testicular content of androgens was undetectable by radioimmunoassay in control animals unless a single injection of LH was given 1 h before death, when androgens were just detectable. Control testes incubated in vitro with [3H]pregnenolone demonstrated that without gonadotrophin stimulation pregnenolone was metabolized only to progesterone in significant amounts. Assay for cholesterol side-chain cleavage cytochrome P450 (P450scc) mRNA showed basal expression in saline-treated hpg mouse testis. LH treatment induced hypertrophy and hyperplasia of Leydig cells and division of germ cells. Testicular androgen content increased significantly, with testosterone and androstenedione as the major androgens. LH-treated testes incubated with [3H]pregnenolone in vitro had a greater synthetic capacity for testosterone, suggesting an increase in 17 alpha-hydroxylase/C17-20-lyase activity. Basal and human chorionic gonadotrophin-stimulated androgen production in vitro increased markedly following LH treatment to levels previously described in the normal adult animal. LH treatment caused a rapid and transient increase in the hybridization of P450scc mRNA which was sevenfold greater than that of saline-treated controls when the animals were killed 1 h after the last injection but fell to control levels within 24 h of cessation of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of injection of gonadotrophin-releasing hormone on testicular steroidogenesis in the hypogonadal (hpg) mouse.

Hypogonadal (hpg) mice were injected once daily with 10 ng, 50 ng or 1 microgram GnRH for 5, 10 or 20 days or 12 times daily with 4.2 ng GnRH for 5 days. Basal and hCG-stimulated production in vitro of androstenedione, testosterone and 5 alpha-androstane-3 alpha,17 beta-diol (androstanediol) were measured by radioimmunoassay. All doses of GnRH increased testicular weight and in-vitro androgen production although seminal vesicle weights were unchanged and serum testosterone concentrations remained undetectable. After 5 days' treatment androstenedione and androstanediol were the dominant androgens produced, the latter indicating the presence of high levels of 5 alpha-reductase. By 20 days testosterone production was predominant after treatment with higher doses of GnRH. Total androgen production (androstenedione + testosterone + androstanediol) after 5 and 10 days was similar at all concentrations of GnRH used. After 20 days' treatment total androgen production was significantly greater with 50 ng GnRH/day than with 10 or 1000 ng/day. Multiple daily injections of 4.2 ng GnRH (total dose 50 ng/day) had no greater effect on androgen production in vitro compared to single daily injections of 50 ng. This suggests that under the conditions used in this study the testis does not require pulsatile release of the gonadotrophins. The pattern of [3H]pregnenolone metabolism was measured after 5 days injection of 50 ng GnRH/day. Compared to control hpg animals there was a significant increase in formation of C19 steroids, synthesis being solely through the 4-ene pathway. These results show that GnRH treatment of hpg mice will induce testicular steroidogenesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Testicular steroid metabolism during development in the normal and hypogonadal mouse.

The patterns of testicular steroidogenesis were investigated during postnatal development in the normal mouse and in the hypogonadal (hpg) mouse from 20 days. The hpg mouse lacks GnRH and may be used to examine the function of this peptide in normal gonadal development. Testicular tissue was incubated with [3H]pregnenolone and metabolites were separated by thin-layer chromatography and high-performance liquid chromatography. In the normal mouse from 1 to 10 days, metabolism occurred predominantly through the delta 4 pathway, and progesterone, 17 alpha-hydroxyprogesterone, androstenedione and testosterone were the main metabolites formed, together with significant amounts of an unidentified polar steroid. Between 15 and 25 days, androstenedione became the major metabolite formed from pregnenolone. There was also a marked increase in 5 alpha-reductase activity during this age range, and 5 alpha-dihydrotestosterone and 5 alpha-androstane-3 alpha, 17 beta-diol were significant metabolites. In normal animals older than 30 days, testosterone became the major metabolite, and between 30 days and adulthood the pattern of metabolism changed significantly due to increased formation of intermediates from the delta 5 pathway. In the hpg mouse between 20 and 30 days, the pattern of steroid metabolism was unlike that of any age of the normal animal. Progesterone was the major metabolite formed and dehydroisoandrosterone was the major C19 steroid formed, although significant levels of androstenedione and testosterone were also formed. After 30 days there was a marked decrease in steroid metabolism, with androstenedione (the major androgen) being formed mainly through the delta 4 pathway.(ABSTRACT TRUNCATED AT 250 WORDS)

Establishing a rehabilitation program for impaired pharmacists.

The Texas Pharmaceutical Association (TPA) rehabilitation program for impaired pharmacists and pharmacy students is described. Since its inception in 1983, the TPA Pharmacists Rehabilitation Program has provided assistance to impaired pharmacists and pharmacy students, as well as their families, friends, customers, and coworkers. The program uses a carefully developed intervention process designed to assist impaired pharmacists and pharmacy students in obtaining evaluation and treatment of their condition. After a referral, an appointment is made for the impaired person at 1 of 15 regional evaluation and referral centers across the state, where arrangements for appropriate treatment are made. After treatment, the Committee on Pharmacists Rehabilitation aids the pharmacist or student in reentering the profession or returning to school. Intervenors are pharmacists registered in the state of Texas who have participated in TPA's training sessions; TPA also provides an intervenor's workbook. Amendments to the Texas Pharmacy Act passed in 1983 and 1985 provide protection for intervenors who are working with pharmacists and pharmacy students with impairment problems. Referrals are made by means of a 24-hour, toll-free hotline funded by a pharmaceutical manufacturing company. Other funding comes from individual donors, member associations affiliated with TPA, chain drugstores, wholesalers, and the Texas State Board of Pharmacy. A successful rehabilitation program for impaired pharmacists and students must be carefully designed and implemented, with attention paid to legal, financial, and intervention-related issues associated with substance abuse.