FEASIBILITY OF CONDUCTING CARDIOVASCULAR OUTCOME RESEARCH IN AUSTRALIAN GENERAL PRACTICE: RESULTS FROM THE ANBP2 PILOT STUDY

1. The present study aimed to determine the feasibility of conducting a 5 year cardiovascular outcome trial of the treatment of 6000 elderly hypertensive patients in Australian general practices. 2. General practitioners (GPs) were invited to participate by mail and personal follow-up. Patient records were reviewed to identify subjects for a blood pressure (BP) screening programme. Blood pressure was measured on three occasions and eligible subjects were included if the average BP was 160 mmHg systolic or 90 mmHg diastolic if systolic BP was 140 mmHg. 3. Seven hundred and forty-one GPs were approached and 89 were enrolled in the study (12% of mail invites and 75% of those receiving a personal contact). In 16 practices where screening was completed, 82 000 records were reviewed to identify 4% patients eligible for screening. Twenty-two per cent of eligible subjects attended screening. Of 1938 subjects screened, 180 (9%) had BP 5=160/90 mmHg. Forty-seven percent of subjects (n = 916) were receiving antihypertensive therapy and 184 (20%) were withdrawn from therapy. One hundred and sixteen (63%) of these subjects had BP return to study entry levels within 6 weeks. Fifty-seven newly diagnosed and 81 previously treated subjects were randomized (7% of the screened population). 4. Based on the high participation rate of GPs, the response rate of patients to attend a BP screening programme and the 7% randomization to screening ratio for entry into the study, the ANBP2 pilot study has demonstrated that it is feasible to recruit subjects from Australian general practices to a cardiovascular outcome trial.     

Ectopic prolactin secretion from a gonadoblastoma

A 6.5-year-old girl developed isosexual, pseudoprecocious puberty secondary to a gonadoblastoma. The tumor was found to produce and secrete both immunoassayable and bioassayable prolactin based on immunohistochemical techniques and the presence of a prolactin gradient between the tumor vein and peripheral vein. The source of the prolactin was a Sertoli-like cell. Neither growth hormone nor growth hormone-releasing hormone was detected within the tumor. This case confirms the ectopic production of prolactin by neoplastic tissue.     

Analysis of epidermal growth factor receptor and activated epidermal growth factor receptor expression in pituitary adenomas and carcinomas.

Epidermal growth factor receptor plays an important role in the pathogenesis of many malignancies. Various growth factors, including epidermal growth factor receptor, have been shown to influence pituitary tumor growth and differentiation. To analyze the role of epidermal growth factor receptor in pituitary tumor development, we examined normal pituitaries (n=8), pituitary adenomas (n=158), and pituitary carcinomas (n=7) for expression of epidermal growth factor receptor protein and messenger RNA using tissue microarrays and RT-PCR. We also examined (a) the expression of phospho-epidermal growth factor receptor, the activated form of epidermal growth factor receptor, in pituitary tumors and normal pituitaries by immunohistochemistry and (b) the effects on epidermal growth factor receptor expression of treating pituitary cells (HP75 cell line) with epidermal growth factor. Epidermal growth factor receptor and the phosphorylated variant expression were present in normal pituitary cells. Epidermal growth factor receptor messenger RNA was also detected in normal pituitaries, pituitary adenomas, and carcinomas by in situ hybridization and RT-PCR. Most pituitary adenomas showed expression of epidermal growth factor receptor and the phosphorylated variant. Nonfunctional adenomas showed higher levels of expression of epidermal growth factor receptor (76 vs 34%) and of phospho-epidermal growth factor receptor (26 vs 8%) as compared to functional adenomas. Five of seven pituitary carcinomas showed strong expression of both epidermal growth factor receptor and phospho-epidermal growth factor receptor. When a human pituitary cell line (HP75) was cultured in the presence of epidermal growth factor receptor, there was an increase in the levels of both epidermal growth factor receptor and phospho-epidermal growth factor receptor after 5 h of treatment, thus confirming that epidermal growth factor receptor signaling was active in pituitary tumors. These results indicate that activated epidermal growth factor receptor is expressed in pituitary adenomas and carcinomas. Higher levels in pituitary carcinomas suggest a role in pituitary tumor progression.     

The functional pathology of hypophyseal adenomas

This review summarizes some aspects of pituitary adenoma pathology. A new embracing pituitary adenoma classification has been developed which correlates morphologic findings with endocrine activity. It is based on hormone content, histologic, immunohistochemical and ultrastructural features, cellular composition and cytogenesis, and separates pituitary adenomas into 7 distinct entities.     

Nonstress test assessment of twins.

Twin pregnancies have higher perinatal morbidity and mortality rates than singleton pregnancies. Researchers have demonstrated that one major benefit of prenatal care in the twin gestation is reduced fetal death rate. This study to determine the relationship of nonstress tests (NSTs) to pregnancy outcome in twin gestations comprised 665 women who delivered at Los Angeles County-University of Southern California Women's Hospital from January 1985 to January 1989. These patients, all of whom had prenatal care (PNC), were subdivided into two groups: (1) PNC and NSTs and (2) PNC and no NSTs. The groups did not differ statistically with regard to gravidity, parity and abortions. NSTs were selectively done on twin gestations complicated by discordancy or other fetal/maternal complications. Ten pregnancies were complicated by fetal demise of one or both twins in patients who received prenatal care without NSTs. Among the NST group there was one fetal demise. Although the NST group had fewer fetal deaths, the reduction was not statistically significant (P = .062). Infant birth weight was identified as a confounder because the NST group had a statistically higher mean birth weight. Definitive proof of the ability of NSTs to reduce the fetal death rate in twin gestations complicated by discordancy or other pregnancy complications awaits a large, prospective, randomized trial.     

Preoperative hemostatic activity and excessive bleeding after cardiopulmonary bypass

The rationale for predicting the risk of excessive postoperative bleeding by assessing the hemostatic status of a patient before cardiopulmonary bypass was investigated. A novel, rapid, overall test (hemostatometry) consisting of a physiologically relevant test of platelet function (shear-induced hemostasis) and coagulation was performed using nonanticoagulated blood and compared with the routine coagulation screen. Two hundred five patients undergoing elective coronary revascularization were studied 3 to 4 days before operation. Forty-nine bled excessively for nonsurgical reasons; none were predicted by the routine coagulation tests. Using a stepwise discriminant analysis, hemostatometry correctly predicted 31 of 49 (63%). Thirty of 156 predicted as bleeders by hemostatometry did not bleed. Thus, preoperative hemostatometry predicted 77% of the true outcome. The false predictions suggest, however, that certain bleeding abnormalities probably acquired during cardiopulmonary bypass cannot be predicted. These findings do not justify the routine use of preoperative tests in assessing the bleeding risk in patients undergoing cardiopulmonary bypass.     

Corticosterone release in response to repeated, short episodes of neonatal isolation : evidence of sensitization

Repeated isolation of neonatal rats produces persistent changes in physiology and behavior. In Experiment 1, we examined changes in plasma corticosterone (CORT) levels as a possible mechanism for the effects of isolation. Pups that were isolated from their mother and the nest for 1 h per day on postnatal days (PND) 2–9 were compared to control litters of pups that were either nonhandled or handled but not isolated. On PND 2, compared to nonhandled pups, handled pups had elevated CORT levels that returned to baseline levels within 30 to 60 min of return to the home cage. No significant elevation of CORT levels were found in handled pups on PND 9. The CORT levels of isolated pups were over twice those of nonhandled pups on PND 2 and four times those of nonhandled pups on PND 9. In Experiment 2, we investigated whether the increased CORT release in response to isolation on PND 9 was the result of the pups treatment on the previous six days as against an effect of maturation. Plasma CORT levels were measured in rat pups that were either isolated, handled or nonhandled on PNDs 2–8 during the conditions of isolation, handling and nonhandling on PND 9. There were no differences among the groups in basal plasma levels of CORT. Handling on PND 9 did not result in elevated CORT levels in any of the groups. All three groups showed a significant increase in plasma CORT levels after isolation on PND 9. However, the CORT response to isolation of pups previously isolated on PND 2–8 were significantly higher than pups that were either handled or nonhandled on PNDs 2–8. Thus, daily episodes of isolation potentiate the hypothalamic-pituitary-adrenal response to stress.     

Infusion of a stable prostacyclin analogue, iloprost, to patients with peripheral vascular disease: lack of antiplatelet effect but risk of thromboembolism.

PURPOSE: Prostacyclin, a potent inhibitor of platelet function and vasodilator, has been used to treat peripheral vascular disease. The aim of this study was to monitor the thrombotic status of patients treated by infusion of a stable prostacyclin analogue, iloprost. PATIENTS AND METHODS: Thirteen patients with peripheral vascular disease underwent iloprost infusion for 3 days (8 hours each day) in a dose ranging from 0.5 to 2 ng/kg/minute. Variable parameters of thrombosis such as platelet reactivity (shear-induced hemostatic plug formation and thrombus formation on a collagen fiber), coagulation, and spontaneous thrombolysis (dislodgment of hemostatic plugs) were measured from non-anticoagulated blood samples by hemostatometry immediately before and 1 hour after the infusion and on the last day, 4 hours after initiation of the infusion. RESULTS: Analysis of data from all patients 1 hour after the infusion showed no changes in platelet reactivity and spontaneous thrombolysis, but coagulation was significantly enhanced. In four patients, significant platelet hyperreactivity was observed after the infusion. Four of the five patients tested while undergoing iloprost infusion showed an enhanced thrombotic reaction and markedly enhanced coagulation. Iloprost employed in vitro in a concentration that corresponds to the therapeutic peak blood level caused no inhibition of platelet function but significantly enhanced coagulation. The threshold in vitro iloprost concentration at which anti-platelet effect and increased spontaneous thrombolysis were observed was twice that of the therapeutic blood level. CONCLUSIONS: These findings challenge the view that antagonism of platelet function is an important factor of iloprost therapy. Furthermore, platelet hyperreactivity in some patients and markedly enhanced coagulation during and after infusion of iloprost in general, represent a risk of thromboembolism, especially as patients are already in a prethrombotic condition.