Objective To evaluate the effect of opt-in compared with opt-out recruitment strategies on response rate and selection bias. Design Double blind randomised controlled trial. Setting Two general practices in England. Participants 510 patients with angina. Intervention Patients were randomly allocated to an opt-in (asked to actively signal willingness to participate in research) or opt-out (contacted repeatedly unless they signalled unwillingness to participate) approach for recruitment to an observational prognostic study of patients with angina. Main outcome measures Recruitment rate and clinical characteristics of patients. Results The recruitment rate, defined by clinic attendance, was 38% (96/252) in the opt-in arm and 50% (128/258) in the opt-out arm (P = 0.014). Once an appointment had been made, non-attendance at the clinic was similar (20% opt-in arm v 17% opt-out arm; P = 0.86). Patients in the opt-in arm had fewer risk factors (44% v 60%; P = 0.053), less treatment for angina (69% v 82%; P = 0.010), and less functional impairment (9% v 20%; P = 0.023) than patients in the opt-out arm. Conclusions The opt-in approach to participant recruitment, increasingly required by ethics committees, resulted in lower response rates and a biased sample. We propose that the opt-out approach should be the default recruitment strategy for studies with low risk to participants.

Plasma CRH was measured in maternal plasma throughout the third trimester of pregnancy, during labor, and postpartum. CRH levels were also measured in arterial and venous umbilical cord plasma samples. In normal pregnant women, plasma CRH increased from 50 +/- 15 (+/- SEM) pg/mL at 28 weeks gestation (n = 41) to 1462 +/- 182 pg/mL at 40 weeks (n = 55) and 1680 +/- 101 pg/mL (n = 65) in labor. Women with pregnancy-induced hypertension (n = 49) had plasma CRH levels significantly elevated above this normal range. Similarly, women who subsequently went into premature labor had raised levels several weeks before the onset of labor. After delivery, plasma CRH returned to normal within 15 h. Total plasma cortisol levels varied little throughout the third trimester, but increased during labor and remained elevated 2-3 days postpartum. There was, therefore, no correlation between plasma cortisol and CRH, implying that this placental CRH is not primarily involved in the control of the maternal hypothalamo-pituitary adrenal axis during pregnancy. The concentrations of CRH in umbilical cord plasma samples were considerably lower than those in the maternal circulation and were close to those in normal nonpregnant adults.

Contributorship and guarantor: MJ conceptualised this article, undertook the literature search and is guarantor. JC used her knowledge of chest radiology to inform the content of the article and sourced the images. JP used his knowledge of assessment and management of covid-19 patients to inform the article. MJ, JC, and JP drafted and checked the final article. Patient consent:We considered seeking individual consent to use radiological images. However, as patients with covid-19 are ill and an infectious risk, obtaining consent was not possible. We approached the hospital ethics committee chair, Trust R&D, and Data Protection lead for permission to use anonymised radiological images without specific consent. They agreed this was acceptable.

alpha-Amylase and hemicellulase, derived from culture of Aspergillus species, are commonly added to flour as improvers during baking. Two cases of women occupationally sensitized to alpha-amylase who developed allergic symptoms after eating baked bread have been reported. With a randomized, controlled study design, we have investigated whether similar responses occur in those sensitized to Aspergillus species. Seventeen subjects with positive skin prick tests to Aspergillus fumigatus were studied. Symptomatic and physiologic responses after ingestion of bread baked with alpha-amylase and hemicellulase were compared, in a crossover fashion, with those after ingestion of bread baked without enzymes. No increase in respiratory or other symptoms, lung function, or nonspecific bronchial hyperreactivity was reported after ingestion of the enzyme-containing bread. We conclude that important clinical reactions to alpha-amylase and hemicellulase in baked bread do not frequently occur in those sensitized to Aspergillus species.

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The stresses of electrical shock or laparotomy were repeated at various intervals up to 24 hr after the initial stress in an attempt to demonstrate inhibition of the second response as a consequence of corticosterone secreted after the first stress. In all cases the second response was equal to or greater in magnitude than the first. When the stress of prolonged (60-90 min) restraint was paired with the minor stress of injection several hr later, no inhibition of the corticosterone response to injection was observed.However, if the plasma corticosterone levels provoked by restraint stress were mimicked by injections of corticosterone or of ACTH, the subsequent response to injection stress was inhibited. We conclude from these, and previous studies in the adrenalectomized rat, that corticosterone does act to inhibit ACTH secretion, but that stress causes a prolonged period of hyper-responsiveness in either CNS or anterior pituitary components of the adrenocortical system. {Endocrinology 92: 1367, 1973) F EEDBACK control of ACTH secretion by circulating corticosteroids has been demonstrated both by the chronic increase in ACTH secretion which follows adrenalectomy and by the inhibition of ACTH secretion after corticosteroid treatment. However, it has been debated whether inhibition of stress-induced ACTH secretion occurs in the rat after treatment with smaller physiological quantities of corticosterone. Some have been unable to detect inhibition of stress responses after small doses of corticosterone (1-3), while others have demonstrated inhibition of stress responses while plasma corticosterone levels are rising as a result of treatment but are still in the low part of the physiological range (4-5). In part, the discrepant results appear to depend on the stress chosen to test for inhibition. It is abundantly clear that within the first few hr

SUMMARY1. The rat hypothalamus (containing the supra-optic nuclei, paraventricular nuclei, median eminence and proximal pituitary stalk) has been incubated in vitro and shown to be capable of releasing the neurohypophysial hormones, oxytocin and arginine vasopressin, at a steady basal rate about one twentieth that of the rat neural lobe superfused in vitro.2. The hypothalamus and neural lobe in vitro released both hormones in a similar arginine vasopressin/oxytocin ratio of about 1P2: 1. However, when release was expressed relative to tissue hormone content, the hypothalamus was shown to release about three times as much arginine vasopressin and six times as much oxytocin as the neural lobe.3. Dopamine in a concentration range of 10-13-10-9 M caused graded increases in hormone release from the hypothalamus in vitro to a maximum fivefold increase over preceding basal levels. The demonstration that apomorphine also stimulated hormone release whereas noradrenaline was relatively ineffective suggested that a specific dopamine receptor was involved. A separate cholinergic component in the release process was indicated by the finding that acetylcholine stimulated release to a maximum fivefold increase in concentrations of 1O-13-1O-9M.4. The fact that the isolated hypothalamus can be stimulated by dopamine and acetylcholine to release increased amount of oxytocin and * Present address and address for reprints:

A new method for measuring mucociliary tracheal transport rates (MTTR's) is described. An aqueous aerosol containing albumin microspheres labeled with 99mTc was inhaled in such a manner that it was deposited in local concentrations in the large airways. These boli of microspheres were transported up the trachea and their MTTR's measured using a gamma camera. MTTR's were measured in 42 healthy nonsmoking adults (32 men and 10 women, mean age 28 yr). The mean MTTR's appeared to be log normally distributed with a geometric mean of 3.6 mm/min and a coefficient of variation of 75%. The MTTR's of men and women were similar. Each individual's short-term coefficient of variation was 25%. Twenty-two repeat studies 1 wk to 15 mo apart showed the variation within individuals was less than between individuals. The parasympatholytic drug, atropine (0.6 mg iv) decreased MTTR's for at least 3 h. Inhalation of the sympathomimetic drug, Th1165a increased MTTR's. Chronic and acute smoking did not appreciably change the MTTR'S.