Transsphenoidal pituitary resection for preoperative diagnosis of prolactin-secreting pituitary adenoma in women: long term follow-up.

The long term efficacy and safety of transsphenoidal resection for preoperative diagnosis of PRL-secreting pituitary adenomas in a large series of women have not been described. Four hundred and nine consecutive women at this university tertiary referral center undergoing transsphenoidal resection for preoperative diagnosis of PRL-secreting pituitary adenoma were followed for a minimum of 4 yr. The objective was to determine the efficacy and morbidity of this procedure and to identify features correlating with the resolution of hyperprolactinemia. Outcome measures included referral, preoperative, surgical, postoperative hospitalization, and long-term follow-up information, including recent PRL concentration. Follow-up was ascertained in 83% of patients who were followed for a mean of 9.2 yr. Recurrence of hyperprolactinemia occurred in 47% of total patients, but in only 16% with a single surgical procedure, histological diagnosis of prolactinoma, and postoperative PRL concentration of 5 ng/mL or less. The best single predictor of cure was postoperative day 1 PRL concentration of 5 ng/mL or less. Eighty-eight percent of women desiring conception conceived within 1 yr. Glucocorticoid-dependent hypopituitarism occurred in 23% of patients undergoing postoperative radiotherapy. There was no operative mortality. Operative morbidity was low. Our experience demonstrates that women undergoing transsphenoidal surgery for diagnosis of PRL-secreting adenoma form a heterogeneous patient population. The best long term results are achieved in the pure prolactinoma group, for whom transsphenoidal resection is generally safe and effective.

Measurement of the scrapie agent using an incubation time interval assay.

The titer of the scrapie agent was determined by measurements of time intervals from inoculation to onset of illness and from inoculation to death. Both intervals were found to be inversely proportional to the size of the dose injected intracerebrally into random-bred weanling Syrian hamsters. The logarithms of the time intervals minus a time factor were linear functions of the logarithm of the inoculum size. The time factors were determined by regression analysis in order to maximize these linear relationships. An equation relating the titer of the inoculum to the dilution of the sample and the length of the time intervals was developed. This equation facilitates the use of a computerized data base. Validation of these relationships was provided by comparing samples for which the agent was measured both by end-point titration and by time interval assay. Agreement between the two methods was generally within +/-0.5 log10 median infective dose units. No differences between the molecular properties of the agents from hamster and murine sources were observed using primarily the incubation time interval method with the former and end-point titration with the latter. The advantages of this new approach based on time interval measurements are considerable with respect to time and resources.

Determination of scrapie agent titer from incubation period measurements in hamsters.

Progress in studies on the scrapie agent has been hampered by the slow and tedious endpoint titration assays in rodents. A new assay based on incubation period measurements has been developed. The incubation period is defined as the time interval from inoculation to the onset of clinically detectable neurological illness or as the interval from inoculation to death. Both of these intervals or incubation periods are inversely proportional to the size of the dose injected intracerebrally into random bred weanling syrian hamsters. The incubation period was found to be a linear function of the logarithm of the inoculum size over a wide range of dosages (10(2) - 10(8) ID50 units). From these studies an equation relating the titer of the inoculum to the dilution of the sample and the length of the incubation period has been developed facilitating the use of a computerized record system. Validation of the assay was provided by comparing samples where the agent was measured both by endpoint titration and incubation period methods. Agreement between the 2 methods was generally within +/- 0.5 log10 ID50 units. In addition, no differences between the molecular properties of the agents from hamster and murine sources have been detected using primarily the incubation period method with the former and endpoint titration with the latter. The advantages of the incubation period assay are considerable with respect to time and economy.