Augmented pituitary corticotropin response to a threshold dosage of human corticotropin-releasing hormone in depressives pretreated with metyrapone.

We studied pituitary corticotropin response to exogenous corticotropin-releasing hormone infusion and attempted to control for the confounding effect of variable serum cortisol levels between depressed and control subjects. If metyrapone was given during the time of day when hypothalamic pituitary adrenal activity was otherwise low, the relative increase in the corticotropin concentration was small. Pituitary response to exogenous corticotropin-releasing hormone can be defined under conditions in which the amount of glucocorticoid-mediated negative feedback present at the level of the pituitary gland is equal in all subjects. When the ambient cortisol level was equalized (and suppressed) in all subjects at the time of study with a threshold dosage of corticotropin-releasing hormone, we found an augmented response to corticotropin-releasing hormone in depressives. This raises the possibility that either increased pituitary sensitivity to corticotropin-releasing hormone or an increased intracellular pool of corticotropin is available for release in subjects with major depressive illness.

Intervention in large bowel carcinogenesis--does screening improve prognosis?

Cancer of the large bowel is the second most common malignant tumour in the western world, with approximately 20,000 new cases registered each year in England and Wales. No improvement in the survival figures has occurred in the past 30 years, and since 1970 the number of deaths per annum in Great Britain has been rising. The prognosis of the disease is related directly to the degree of centrifugal spread of the tumour. Patients with cancer limited to the bowel wall have a corrected 5-year survival of about 90%, whereas those with tumours with lymphatic spread have a 5-year survival of about 30%. The prognosis for early colorectal tumours is therefore good, but a method of identifying such lesions is required. If early tumours bleed, the detection of occult blood in the faeces may be a valuable screening test for colorectal cancer. In one town, 8,925 asymptomatic people over the age of 40 were invited to be screened for faecal occult bleeding using Haemoccult slides. The invitation was accepted by 2,439 patients, a compliance rate of 27%. On Haemoccult screening 121 patients were positive initially, but 39 of these were found to be false-positive after further investigation. Haemoccult therefore gives a false-positive incidence of 30%. Twelve tumours of the bowel were identified, eight polyps and four cancers. Another patient who had been negative in the screening survey was identified within 2 months of the end of the experiment as having large-bowel cancer. This means that Haemoccult gives a false negative rate, in our hands, of 20%. The ability of a cancer screening procedure to identify and cure early tumours depends upon the compliance of the population, the sensitivity of the test and the availability of effective treatment. The poor compliance of our population and the disappointing sensitivity of Haemoccult mean that occult blood screening for early large bowel cancer remains theoretically possible but practically inefficient.

A sensitive open field measure of anxiolytic drug activity.

Anxiolytic drugs including diazepam (DZP), chlordiazepoxide (CDX), pentabarbitol (PB) and ethanol (EtOH) produce specific alterations in the behavior of fasted rats given access to a single food pellet secured in the center of a novel open field environment. These drugs increase the total amount of food eaten in a 15 min test and the mean amount eaten per approach to the food pedestal. This latter effect appears to be the more sensitive index of anxiolytic drug action and occurs at doses which have no effect on rearing or grooming. DZP was effective following either acute or chronic (15 day) treatment at doses which have no effect on the food consumption by fasted rats tested in their home cages. The effects of the sedative benzodiazepine, flurazepam, were similar to those of DZP but were not statistically significant. Behavioral effects similar to those of DZP were seen in animals receiving additional handling prior to testing or in animals habituated to the open field. Neither the anti-psychotic haloperidol nor morphine mimicked the actions of DZP.

Colonoscopy in surgical practice.

Colonoscopy is a rewarding new technique with a potential for early and more accurate diagnosis. One hundred and seventy colonoscopies carried out over the past three years showed or confirmed colonic cancer in 14 patients, and solitary or multiple colonic polyps were found in 28 cases, of which 18 were excised endoscopically. A large villous adenoma was diagnosed in one patient, and the absence of a suspected sinister lesion was shown by direct examination and biopsy in 110 cases. There were 17 examination failures, including two perforations of the bowel. Colonoscopy complements rather than supplants barium enema examination and will make diagnostic laparotomy for colonic lesions unnecessary. The use of the diathermy snare allows endoscopic removal of colonic polyps and should greatly reduce the need for formal surgery in these cases. The financial saving to the Health Service will greatly outweigh the expense of the procedure, but it should be undertaken only in well organised centres as a specialist service for selected patients. In skilled hands it is safe, but potential hazards exist for the inexperienced endoscopist.