Three types of alpha-melanocyte-stimulating hormone: bioactivities and half-lives.

Three types of alpha-melanocyte-stimulating hormone (alpha MSH) that differ in the acetyl status of the N-terminal serine have been found in the neurointermediate lobe of the pituitary gland and in the brain: desacetyl alpha MSH, which lacks an acetyl group; monoacetyl alpha MSH, in which the amino group of the serine is acetylated; and diacetyl alpha MSH, in which both amino and hydroxy groups of the serine are acetylated. We compared the lipolytic and melanotropic actions of these three peptides, and their rates of disappearance from plasma, both in vitro and in vivo. The following differences were found. a) For in vitro lipolytic actions on rabbit adipose tissue slices, the potencies differed according to the order diacetyl = monoacetyl greater than desacetyl. On rabbit isolated adipocytes, however, the three peptides were equipotent. b) For in vivo lipolytic action in the rabbit, not only potency but also kinetics differed. Diacetyl alpha MSH had the slowest onset, longest duration, and greatest potency. The desacetyl variant had the quickest onset, shortest duration, and least potency. c) The half-life for elimination from rabbit plasma both in vitro and in vivo was shortest for the desacetyl form and longest for the diacetyl peptide. d) For in vitro melanotropic effect on frog skin, kinetics of action were the same for all three peptides, but potency differed according to the order diacetyl = monoacetyl greater than desacetyl. Thus acetylation of alpha MSH alters lipolytic and melanotropic potencies in vitro and lipolytic potency and kinetics in vivo. These differences result in part from the fact that acetylation slows the degradation of the tridecapeptide both inside and outside the circulation.

Rationale for and design of the National Eye Institute Prospective Evaluation of Radial Keratotomy (PERK) Study.

A five-year, multicenter, collaborative clinical trial of radial keratotomy for myopia is being carried out at nine clinical centers. The study, funded by the National Eye Institute, is recruiting approximately 500 patients aged 21 years or older with -2.00 to -8.00 diopters of physiologic myopia who also meet other clearly defined eligibility criteria. Surgeons use a diamond-bladed micrometer knife to make eight radial incisions in the anterior cornea. The diameter of the central clear zone is determined by the amount of myopia and the depth of the incisions by intraoperative ultrasonic pachymetry. Investigators other than the surgeon gather all pre- and post-operative data. Examinations include measurement of visual acuity with standardized charts, verification of refractions by a second observer, measurement of corneal curvature by keratometry and photokeratoscopy, quantitation of glare with a glare tester, and measurement of the size of individual endothelial cells from specular photomicrographs with a computerized digitizer. A formal psychometric questionnaire is used to evaluate the patients' subjective response. Physician monitors insure adherence to the protocol during site visits and members of the Data and Safety Monitoring Board oversee the progress of the study. Biostatisticians at the Coordinating Center insure complete data collection, process the data, and assist in the interpretation of results.

Epinephrine deficiency in hypocorticotropic hypopituitary children.

In rats, adrenal medullary synthesis of epinephrine is impaired by ACTH deficiency and is not improved by replacement doses of glucocorticoid. We have evaluated plasma epinephrine and norepinephrine concentrations in 43 children, 8-15 yr old. These children were divided into 5 groups, with 6-10 per group: normals; children with isolated GH deficiency; hypopituitary children deficient in both GH and TSH; hypopituitary children deficient in GH, TSH, and ACTH; and short children without known organic disease. The deficiencies of ACTH and TSH were being treated with replacement doses of cortisol and T4. Plasma catecholamines were measured in the supine position at rest every other hour from 0800-1600 h, and after exercise in the standing position at 1000 h. Plasma norepinephrine levels, both at rest and after exercise, were normal in all four groups of short children. Resting and postexercise plasma epinephrine levels were reduced to 10-20% of normal in the hypocorticotropic hypopituitary patients, and were normal in the other three groups of short children.

A method of screening for growth hormone deficiency using anthropometrics.

Among children less than 3rd percentile in height, less than 1% are deficient in endogenous growth hormone, while 80% have no recognizable organic cause for short stature, and are termed normal variants. This study investigated whether anthropometric evaluation can distinguish growth hormone-deficient from normal variant children. Height, weight, midarm circumference and 10 skinfold thicknesses were measured in 24 growth hormone-deficient and 26 normal variant children; indices of linear growth, adiposity, and lean body mass were derived from these. All these variables were analyzed statistically by discriminant analysis. This led to a screening formula, here called a "Z-function," based only on height and five skinfolds (abdomen, back, chest, knee, and calf). The Z-function classified correctly all but two growth hormone-deficients and two normal variants. Because of the small and possibly inhomogeneous sample, the particular formula developed here is not recommended for general use, but these preliminary findings show that a simple anthropometric screening test is indeed feasible, and could be useful in pediatric practice.

Effect of total parenteral nutrition on survival in advanced colon cancer.

To determine if total parenteral nutrition (TPN) with constant infusion of hypertonic glucose and amino acids by central vein (35 kcal/kg/day) would influence survival in advanced colorectal carcinoma, 50 patients were randomized to receive either chemotherapy alone or the same drugs plus TPN for 14 days before treatment and a variable period thereafter. Overall median survival was significantly decreased in the TPN patients (79 vs 305 days, P = 0.03). Survival was significantly decreased in the TPN patients who had lost the least percentage of premorbid weight (0-6%) (66 vs 398 days, P = 0.02), and in all TPN males (61 vs 209 days, P = 0.03), when compared to similar controls. TPN did not increase survival in any patient subcategory. Catheter-related and metabolic complications were uncommon. We conclude that TPN as used in this study did not prolong median survival in the group as a whole, and may have shortened survival in males and in patients with little or no prior weight loss.