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Biomedical subjects

R Fossati

Publications and source records attributed to R Fossati.

At least 19 recordsLinked to original sources

Randomised study of systematic lymphadenectomy in patients with epithelial ovarian cancer macroscopically confined to the pelvis.

No randomised trials have addressed the value of systematic aortic and pelvic lymphadenectomy (SL) in ovarian cancer macroscopically confined to the pelvis. This study was conducted to investigate the role of SL compared with lymph nodes sampling (CONTROL) in the management of early stage ovarian cancer. A total of 268 eligible patients with macroscopically intrapelvic ovarian carcinoma were randomised to SL (N=138) or CONTROL (N=130). The primary objective was to compare the proportion of patients with retroperitoneal nodal involvement between the two groups. Median operating time was longer and more patients required blood transfusions in the SL arm than the CONTROL arm (240 vs 150 min, P<0.001, and 36 vs 22%, P=0.012, respectively). More patients in the SL group had positive nodes at histologic examination than patients on CONTROL (9 vs 22%, P=0.007). Postoperative chemotherapy was delivered in 66% and 51% of patients with negative nodes on CONTROL and SL, respectively (P=0.03). At a median follow-up of 87.8 months, the adjusted risks for progression (hazard ratio [HR]=0.72, 95%CI=0.46-1.21, P=0.16) and death (HR=0.85, 95%CI=0.49-1.47, P=0.56) were lower, but not statistically significant, in the SL than the CONTROL arm. Five-year progression-free survival was 71.3 and 78.3% (difference=7.0%, 95% CI=-3.4-14.3%) and 5-year overall survival was 81.3 and 84.2% (difference=2.9%, 95% CI=-7.0-9.2%) respectively for CONTROL and SL. SL detects a higher proportion of patients with metastatic lymph nodes. This trial may have lacked power to exclude clinically important effects of SL on progression free and overall survival.

Adult↗

Adjuvant chemotherapy vs radiotherapy in high-risk endometrial carcinoma: results of a randomised trial.

Patients with high-risk endometrial carcinoma (stage IcG3, IIG3 with myometrial invasion >50%, and III) receive adjuvant therapy after surgery but it is not clear whether radiotherapy (RT) or chemotherapy (CT) is better. We randomly assigned 345 patients with high-risk endometrial carcinoma to adjuvant CT (cisplatin (50 mg m(-2)), doxorubicin (45 mg m(-2)), cyclophosphamide (600 mg m(-2)) every 28 days for five cycles, or external RT (45-50 Gy on a 5 days week(-1) schedule). The primary end points were overall and progression-free survival. After a median follow-up of 95.5 months women in the CT group as compared with the RT group, had a no significant hazard ratio (HR) for death of 0.95 (95% confidence interval (CI), 0.66-1.36; P = 0.77) and a nonsignificant HR for event of 0.88 (95% CI, 0.63-1.23; P = 0.45). The 3, 5 and 7-year overall survivals were 78, 69 and 62% in the RT group and 76, 66 and 62% in the CT group. The 3, 5 and 7-year progression-free survivals were, respectively, 69, 63 and 56 and 68, 63 and 60%. Radiotherapy delayed local relapses and CT delayed metastases but these trends did not achieve statistical significance. Overall, both treatments were well tolerated. This trial failed to show any improvement in survival of patients treated with CT or the standard adjuvant radiation therapy. Randomised trials of pelvic RT combined with adjuvant cytotoxic therapy compared with RT alone are eagerly awaited.

Aged↗

Follow-up strategies for women treated for early breast cancer.

BACKGROUND: Follow-up examinations are commonly performed after primary treatment for women with breast cancer. They are used to detect recurrences at an early (asymptomatic) stage. OBJECTIVES: To assess the effectiveness of different policies of follow-up for distant metastases on mortality, morbidity and quality of life in women treated for stage I, II or III breast cancer. SEARCH STRATEGY: We searched, the Breast Cancer Group's specialized register (May 14, 2004), the Cochrane Controlled Trial Register (Cochrane Library Issue 1, 2004), Medline (January 1966 - May 2004) and EMBASE (1988 - May 2004). References from retrieved articles were also checked. SELECTION CRITERIA: All randomised controlled trials (RCTs) assessing the effectiveness of different policies of follow-up after primary treatment were reviewed for inclusion. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and eligibility for inclusion in the review. Data were pooled in an individual patient data meta-analysis for the two RCTs testing the effectiveness of different follow-up schemes. Subgroup analyses were conducted by age, tumour size and lymph node status. MAIN RESULTS: Four RCTs involving 3055 women with breast cancer (clinical stage I, II or III) were included. Two of these involving 2563 women compared follow-up based on clinical visits and mammography with a more intensive scheme including radiological and laboratory tests. After pooling the data, no significant differences in overall survival (hazard ratio 0.96, 95% confidence interval 0.80 to 1.15) or disease-free survival (hazard ratio 0.84, 95% confidence interval 0.71 to 1.00) emerged. No differences in overall survival and disease-free survival emerged in subgroup analyses according to patient age, tumour size and lymph node status before primary treatment. In 1999, 10-year follow-up data became available for Rosselli Del Turco and no significant differences in overall survival were found. One RCT (296 women) compared follow-up performed by a hospital-based specialist to follow-up performed by general practitioners. No significant differences in time to detection of recurrence and quality of life emerged. Patient satisfaction was greater among patients treated by general practitioners. One RCT (196 women) compared regularly scheduled follow-up visits to less frequent visits restricted to the time of mammography. No significant differences emerged in interim use of telephone and frequency of GP's consultations. AUTHORS' CONCLUSIONS: This updated review of RCTs conducted almost 20 years ago suggest that follow-up programs based on regular physical examinations and yearly mammography alone are as effective as more intensive approaches based on regular performance of laboratory and instrumental tests in terms of timeliness of recurrence detection, overall survival and quality of life. In one RCT, follow-up care performed by trained general practitioners working in an organized practice setting had comparable effectiveness to that delivered by hospital-based specialists in terms of quality of life and time to detection of distant metastases.

Breast Neoplasms↗

Randomised controlled trial comparing single agent paclitaxel vs epidoxorubicin plus paclitaxel in patients with advanced ovarian cancer in early progression after platinum-based chemotherapy: an Italian Collaborative Study from the Mario Negri Institute, Milan, G.O.N.O. (Gruppo Oncologico Nord Ovest) group and I.O.R. (Istituto Oncologico Romagnolo) group.

The aim of the study was to evaluate the role of epidoxorubicin plus paclitaxel combination (ET) vs single agent paclitaxel (T), as second-line chemotherapy treatment in advanced ovarian cancer patients in early progression within 12 months after platinum-based chemotherapy. From October 1994 up to June 1999, 234 patients from 34 Italian hospitals were randomised to receive: (A) epidoxorubicin (E) 80 mg m(-2) + paclitaxel (T) 175 mg m(-2) (3 h infusion), every 21 days for 4-6 cycles. (B) Paclitaxel 175 mg m(-2) (3 h infusion) every 21 days for 4-6 cycles. Evaluable for survival analysis were 106 and 106 patients in ET and T arm, respectively. Platinum-based monochemotherapy was the first-line treatment in 43% patients, while polichemotherapy containing anthracyclines was the preferred first-line therapy in 22% patients. The median time from the end of first-line therapy to randomisation was 3 months. Treatment was completed in 87 and 85% of T and ET arm, respectively. Haematological toxicity was significantly more common in ET group (ECOG grade 3-4 neutropenia: 37.4% in ET vs 18.2% in T arm). Neuropathies were similar in both arms (sensory: ECOG grade 2-3: 12.1% in ET vs 14.7% in T arm, motor: 6.1% in ET vs 5.3% in T arm). Objective response was achieved in 37.4% of patients in ET group and in 46.9% of patients in T arm. At a median follow-up of time of 48 months, a total of 180 patients progressed and 163 patients died. Survival analysis showed no difference between ET and T (median time to progression: 6 months for both regimens, median survival: 12 and 14 months for ET and T, respectively; hazard ratio for mortality of ET vs T: 1.17 (95% CI 0.86-1.59; P=0.33). The ET regimen does not seem to be more effective than T in refractory advanced ovarian cancer patients in early progression after platinum-based chemotherapy. Despite an acceptable response rate, the control of disease progression remains poor.

Adult↗

Does a drug do better when it is new?

BACKGROUND: When assessing a new, promising therapeutic approach, a clinician's perception of a drug's effectiveness may be shaped by different kinds of phenomena, and among them, a favorable attitude towards new treatments, and as a result a tendency to overestimate their efficacy (wish bias). MATERIALS AND METHODS: A retrospective study of published randomized clinical trials of doxorubicin-based chemotherapy for advanced breast cancer was carried out. Global (complete plus partial) response rate over time with allowance for type of drug regimen (mono- or polychemotherapy) and prior adjuvant therapies was assessed in the doxorubicin-containing arm using multivariate logistic regression analysis. RESULTS: Twenty-nine studies published from 1975 to 1999 were retrieved for a total of 2234 women with advanced breast cancer enrolled in the doxorubicin-containing arms. There was a significant decrease in response rate to doxorubicin as first-line treatment over time that resisted adjustment for important differences in therapeutic management [odds ratio for global response = 0.89, 95% confidence interval (CI) 0.81 to 0.99]. CONCLUSIONS: Although only one drug (doxorubicin) in one clinical context (advanced breast cancer) has been analyzed, our findings support the use of double blind methodology whenever possible when assessing subjective endpoints and encourage further studies aimed at defining the clinical relevance of a wish bias in medicine.

Antineoplastic Agents↗

The performance of SF-36 health survey in patients with laryngeal cancer. Head and Neck Cancer Italian Working Group.

BACKGROUND: Interest in measuring health-related quality of life has increased together with the awareness that such humanistic outcomes require valid and reliable measures. Among the several generic questionnaires, the Short Form 36 Items Health Survey (SF-36) is recognized for its comprehensiveness, brevity, and high standards of reliability and validity. It has been translated and validated in several languages. METHODS: In the framework of a larger, prospective, multicenter study aimed to produce and validate an Italian questionnaire tailored to laryngeal cancer patients, the SF-36 was administered to a sample of well-characterized cases. It was, therefore, possible to test its characteristics in terms of patients' acceptance, psychometric, and clinical validity. RESULTS: Overall, findings show that in this sample of 165 consecutive patients with laryngeal cancer at various stage of disease, the SF-36 performance was very good. The patients' acceptance was satisfactory: all patients completed the questionnaire. All the questionnaire scales met the standards suggested in terms of grouping and scaling assumptions. The internal reliability coefficients actually replicate the satisfactory findings reported for the original SF-36. In terms of capability of the questionnaire scales to discriminate between groups expected to differ in a given health concept in relation to clinical variables, the results were also good. CONCLUSIONS: This study showed that SF-36 was well accepted by patients and was able to detect the impact of different treatment approaches on health- related quality of life. It is likely that the sensitivity and the precision of the SF-36 can be further improved by integrating brief questionnaire modules specific for laryngeal clinical issues.

Adaptation, Psychological↗

Follow-up strategies for women treated for early breast cancer.

BACKGROUND: Follow-up examinations are commonly performed after primary treatment for women with breast cancer. They are used to detect recurrences at an early (asymptomatic) stage. OBJECTIVES: To assess the effectiveness of different policies of follow-up for distant metastases on mortality, morbidity and quality of life in women treated for early breast cancer. SEARCH STRATEGY: We searched the Breast Cancer Groups specialised register, the Cochrane Controlled Trials Register ( Cochrane Library Issue 4, 1999), MEDLINE (January 1975-September 1999) and EMBASE (1988-September 1999) using "Breast Neoplasms" and "follow-up". References from retrieved articles were also checked, as were the lists of presentations from recent breast cancer meetings. SELECTION CRITERIA: All randomised controlled trials (RCTs) assessing the effectiveness of different policies of follow-up after primary treatment were reviewed for inclusion. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and eligibility for inclusion in the review. Data were pooled in an individual patient data meta-analysis for the two RCTs testing the effectiveness of different follow-up schemes. Subgroup analyses by age, tumour size and lymph node status before primary treatment are also presented. MAIN RESULTS: Four RCTs involving 3204 women with early breast cancer (clinical stage I, II or III) have been included. Two RCTs involving 2563 women compared follow-up based on clinical visits and mammography with a more intensive scheme including radiological and laboratory tests. After pooling the data, no significant differences in overall survival (hazard ratio 0.96, 95% confidence interval 0.80 to 1.15) or disease-free survival (hazard ratio 0.84, 95% confidence interval 0.71 to 1.00) emerged. No differences in overall survival and disease-free survival emerged in subgroup analyses according to patient age, tumour size and lymph node status before primary treatment. One RCT (296 women) compared follow-up performed by a hospital-based specialist to follow-up performed by general practitioners. No significant differences in time to detection of recurrence and quality of life emerged. One RCT (196 women) compared regularly scheduled follow-up visits to less frequent visits restricted to the time of mammography. No significant differences emerged in interim use of telephone and frequency of GP's consultations. REVIEWER'S CONCLUSIONS: Follow-up programs based on regular physical examinations and yearly mammography alone appear to be as effective as more intensive approaches based on regular performance of laboratory and instrumental tests in terms of timeliness of recurrence detection, overall survival and quality of life. In one RCT, follow up care performed by general practitioners had comparable effectiveness to that delivered by hospital based specialists in terms of quality of life and time to detection of distant metastases.

Breast Neoplasms↗

Cytotoxic and hormonal treatment for metastatic breast cancer: a systematic review of published randomized trials involving 31,510 women.

PURPOSE: A systematic review of randomized clinical trials (RCTs) was undertaken to assess the effectiveness of medical treatment for metastatic breast cancer. METHODS: RCTs published between 1975 and 1997 have been classified according to 12 therapeutic comparisons: (1) polychemotherapy (PCHT) agents versus single agent; (2) PCHT regimens with anthracycline versus PCHT without anthracycline; (3) other PCHT versus cyclophosphamide, methotrexate, and fluorouracil (CMF); (4) chemotherapy (CHT) with epirubicin versus CHT with doxorubicin; (5) CHT versus same CHT delivered with less intensive schedules; (6) other endocrine therapy (OET) versus tamoxifen; (7) OET plus tamoxifen versus tamoxifen alone; (8) OET versus medroxyprogesterone; (9) OET versus aromatase inhibitors; (10) OET versus megestrol; (11) endocrine therapy (ET) versus same ET at lower doses; and (12) CHT plus ET versus CHT. Tumor response rates, mortality hazards ratio (HR) and frequency of severe side effects were the outcome measures. RESULTS: A total of 189 eligible trials (31,510 patients) were identified. All provided response rates and 133 (70%) data or survival curves needed for calculation of the HR. In eight of 12 comparisons, statistically significant differences for response emerged (1, 2, 3, 5, 7, 8, 11, 12); all but no. 8 favored the first term of the comparison. Overall survival analysis showed better results of (a) PCHT versus single-agent CHT (HR=0.82; 95% confidence interval [CI], 0.75 to 0.90); (b) CHT with doxorubicin versus CHT with epirubicin (HR=1.13; 95% CI, 1.00 to 1.27); (c) CHT versus the same CHT delivered with less intensive schedules (HR=0.90; 95% CI, 0.83 to 0.97); (d) ET versus the same ET at lower doses (HR=0.86; 95% CI, 0.77 to 0.97). Quality of life was measured in only 2,995 of 31,510 patients (9.5%). CONCLUSION: Despite some evidence of effectiveness of specific regimens, the relevance of these findings is limited by the modest survival benefit and the lack of evaluation of the quality-of-life impact of these treatments.

Antibiotics, Antineoplastic↗

Appropriateness of the use of clinical and radiologic examinations and laboratory tests in the follow-up of surgically-treated breast cancer patients. Results of the Working Group on the Clinical Aspects of Follow-up.

BACKGROUND: The aim of this working group was to assess the appropriateness of use of radiologic examinations, laboratory tests and periodic check-ups for surgically-treated, disease-free breast cancer patients. MATERIALS AND METHODS: A total of 252 clinical scenarios (36 for each of the 8 exams considered: clinical examination, mammography, chest roentgenography, hematochemical tests, markers, bone scan, liver echography/abdominal CT scan), each representing a specific surgically treated and disease-free breast cancer patient, were rated by the members of the panel. A 3 point scale was utilized as to whether the test in question was judged inappropriate (1), questionable (2), or appropriate (3) (in the latter case the panel member was also asked for the advised frequency of the exam expressed in months). RESULTS: After two assessment sessions, consensus among members of the panel was reached on 216 of the 252 scenarios; disagreement remained on only 36 clinical scenarios. CONCLUSIONS: The panel agreed that only clinical examinations and mammographies should be recommended for routine clinical follow-up of surgically-treated breast cancer patients. Given the current available therapeutic options, these would assure adequate medical care and psychological aid.

Aged↗

Breast cancer surgery in 30 Italian general hospitals.

The utilization of limited surgery in patients with breast cancer operated between September 1986 and July 1988 was assessed using information collected within a cohort subsequently enrolled in a randomized clinical trial testing the efficacy of post-surgical follow up. Overall 30% had limited surgery, 61% had other more radical procedures and 9% are still undergoing an unnecessary Halsted mastectomy. Several factors were related to the lower likelihood of getting a conservative procedure: geographic distribution, age, level of education, quadrant and nodal state. The paper discusses the implications of these findings in view of the otherwise growing consensus that more radical surgery should be abandoned.

Breast Neoplasms↗

The role of attitudes, beliefs, and personal characteristics of Italian physicians in the surgical treatment of early breast cancer.

The influence of Italian physicians' attitudes, beliefs, and personal characteristics on medical decision making is examined in the case of surgical treatment of early breast cancer. Responses to a mail survey of 657 physicians from different specialties were analyzed comparing doctors recommending a radical procedure (9%) to those preferring a conservative procedure for younger patients only (25%), and those considering conservative surgery the treatment of choice regardless of patients' age (66%). The findings suggest that the likelihood of physicians' preferring a conservative procedure is influenced by their specialty and the extent to which they feel that a patient should have a role in the treatment decision more than by differences in the beliefs of treatment outcomes. Only preferences of the small group indicating radical surgery as the sole admissible treatment can be accounted for by ignorance or distrust of results of recent trials. These findings suggest that other than scientific factors guide many doctors in their decision making; they may help to explain why the diffusion of research results into clinical practice is often disappointingly slow.

Adult↗

Trends in patterns of care for breast cancer in Italy (1979-1987).

We reviewed care delivered to about 2,500 breast cancer patients in general hospitals over the period 1979-1987 using data from three surveys. The most important and consistent failure was in diagnostic timeliness: about one out of four patients was diagnosed six or more months after the first symptom leading to an almost doubled probability of being diagnosed with more advanced disease. Acceptance of treatment recommendations seemed less satisfactory for surgery than for adjuvant treatments. Conservative surgery still appeared to have limited acceptance for patients with small primary tumor (21 and 23% in 1983 and 1987, respectively) although, starting 1983, there was a shift from the Halsted to the Patey type of radical mastectomy. Follow-up was routine in most node-negative patients and adjuvant chemotherapy was already well established treatment for most pre-menopausal node-positive women (64, 79 and 76% in 1979, 1983 and 1987, respectively). Some form of adjuvant treatment in post-menopausal node-positive women was already present in 1983 but became more widespread in 1987 (82%): this being mostly accounted for by the increase in the use of tamoxifen (delivered alone or in combination with chemotherapy to 53% of women). Overall, our results suggest that areas of care more dependent on organization or doctors' and patients' education (i.e. diagnostic timeliness and accessibility) are those where deficiencies seen to be least amenable to change in the absence of concerted intervention. Among more narrowly defined clinical issues, there appeared to be some dissonance between the rapid acceptance of adjuvant treatments and the still slow pace of acceptance of less aggressive procedures by surgeons.

Breast Neoplasms↗

The impact of cancer treatment guidelines on actual practice in Italian general hospitals: the case of ovarian cancer.

Over the past ten years the Italian National Research Council (C.N.R.) has carried out an educational program based on the preparation and dissemination of guidelines to facilitate delivery in community hospitals of the most up-to-date care to patients with ovarian cancer. In 1988 an assessment was begun to determine (a) whether the guidelines reached the target physician population; (b) whether they were accepted by those they reached, and (c) whether treatment patterns thereafter conformed to the guidelines. Overall results of this evaluation provide no evidence of clinically relevant effects of the program. The guidelines were not widely disseminated: only 44% of responders were aware of them. Moreover, analysis of practice patterns showed serious deficiencies in diagnostic procedure and surgical staging (information on grading and residual tumour was available only in 30% and 45% of cases, respectively, and only 10% of the patients had random biopsies as part of their surgical staging). The only observation supporting some effect of this educational intervention in terms of knowledge modification was of certain therapeutic preferences among those aware of the guidelines. This finding, however, is highly susceptible to confounding by other factors (e.g. physicians' greater expertise, spillover effect of the program) not entirely avoidable in an observational study. We conclude that any assessment of procedures based on dissemination of information must include a careful analysis of the method of dissemination. The availability of clinically applicable information must also be realistically appraised before the guidelines approach can be accepted as the most effective.

Adult↗

Quality of care assessment for breast cancer: how to measure benefits of prevention and therapy in oncology.

Over the last few years evaluation of quality of diagnostic and therapeutic care has become one of the most controversial and fastest growing fields of research in many areas of medicine. In this situation, oncology represents a model case as the conditions in which new therapeutic strategies are tested and implemented largely differ from routine practice, both in terms of availability of sophisticated technology and comparability of patient populations. The promising role of health care research for the understanding of factors through which research advances can be generalized to routine clinical practice has only recently being appreciated. From this point of view, the paper discusses the rationale and key findings of a multi-annual++ evaluation program on breast cancer care, underway in Italy since 1980. Special attention is given to how results (such as data on diagnostic delay or non-adherence to recommended treatment guidelines) can be used for the implementation of educational programs, controlled studies and ad hoc demonstration projects.

Breast Neoplasms↗

Evidence against a self-inhibition of ACTH secretion in man.

To ascertain the physiological relevance of an autoregulation of adrenocorticotropin hormone(ACTH) secretion in man, we studied the effect of alsactide (beta-Ala1, Lys17-ACTH1-17-4-amino-N-butylamide), a synthetic ACTH analogue with potent steroidogenic activity but not recognized in the endogenous ACTH immunoassay, on plasma ACTH pattern in patients with Addison's disease. Three experimental models were employed as follows: (a) in 6 patients, whose steroid replacement therapy had been discontinued 36 h previously, we compared the effect of alsactide, administered at two dose levels (10 or 100 micrograms i.v. als bolus followed by the same dose infused over 2 h, and of placebo, on the plasma ACTH pattern; (b) the previous experiment was repeated in 4 patients in whom cortone replacement therapy was substituted for 3 days with dexamethasone, 0.5-1.5 mg daily p.o., so as to lower plasma ACTH levels to within the high normal range; (c) in 4 patients off therapy for 36 h, we evaluated the ACTH response to synthetic ovine corticotropin-releasing factor, 1 microgram/kg body weight injected intravenously, occurring during concomitant administration of alsactide, 100 micrograms i.v. as bolus plus 100 micrograms infused over 2 h, or placebo. Compared to placebo, alsactide did not significantly affect the pattern of ACTH under any of the experimental conditions investigated. Collectively, our findings, although they have to be interpreted with caution, do not support the idea that a self-regulation mechanism plays an important role in the control of ACTH secretion in man.

Addison Disease↗

Inhibition by phospholipid liposomes of the prolactin and cortisol response to insulin hypoglycemia in man.

This study was designed to further investigate the purported dopaminergic activity of phospholipid liposomes (PL) prepared from bovine cerebral extracts, and to obtain further indications about their pituitary or suprapituitary site of action. In eight normal subjects, we have studied the effects of PL administration (250 mg as IV bolus plus additional 250 mg infused IV over a 60-min period), compared to placebo, on the prolactin (PRL), cortisol and growth hormone (GH) response to an insulin tolerance test (ITT). In eight additional subjects, the effects of PL on the PRL and TSH response to TRH were evaluated. PL medication blunted the PRL and cortisol response in the ITT: significant differences, with respect to placebo administration, were observed between mean peak PRL values (51.9 +/- 13.63 SEM vs 83.4 +/- 26.35 ng/ml, P less than 0.05) and mean cortisol values at 120 min time (20.9 +/- 0.67 vs 26.7 +/- 2.46 micrograms/dl, P less than 0.05). In contrast, PL administration did not modify the ITT-related GH rise or the PRL and TSH release in response to TRH. These findings favour the view that PL are endowed with intrinsic biological activity which is dopamine-mediated, and point to the hypothalamus as their primary site of action.

Adolescent↗

Effect of CRF on the release of anterior pituitary hormones in normal subjects and patients with Cushing's disease.

Patterning of plasma ACTH, beta-EP/beta-LPH and cortisol in response to ovine CRF (1 microgram/kg b.w.t. injected i.v.), was studied in three normal subjects and in five patients with Cushing's disease, two of whom had undergone total bilateral adrenalectomy. CRF caused in all subjects a prompt and concurrent rise of plasma hormone levels. The hormonal response was of the same magnitude in normal controls and in the three untreated Cushing's patients, but was much greater in the two adrenalectomized subjects. No changes were noted, after CRF, in plasma levels of GH, PRL, TSH, LH and FSH. These findings indicate that CRF specifically promotes the pituitary release of ACTH and ACTH-related peptides both in normal subjects and patients with Cushing's disease. In view of the likely CRF hypersecretion of the adrenalectomized patients, their ACTH and beta-EP/beta-LPH hyperresponsiveness to exogenous CRF would denote that the peptide does not down regulate its own pituitary receptors.

Adolescent↗