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Biomedical subjects

J D Neill

Publications and source records attributed to J D Neill.

At least 109 records · Page 6Linked to original sources

Observations on some properties of a long-acting preparation of propranolol.

1. The effects of 160 mg of propranolol and 160 mg of a long-acting (LA) formulation of propranolol were studied in healthy subjects. 2. Both drugs reduced an exercise tachycardia but the peak was less and the 24 h effect greater after long-acting propranolol than after propranolol. 3. These differences were maintained on repeated dosing for 8 days. 4. In contrast to single doses of 400 mg of sotalol, 160 mg of oxprenolol and 160 mg of slow-release oxprenolol, the peak effect of long-acting propranolol was less and that at 24 h was greater.

Adult↗

Dopamine levels in hypophysial stalk plasma of the rat during surges of prolactin secretion induced by cervical stimulation.

Tonic hypothalamic inhibition of PRL release is partially explainable by dopamine secretion into hypophysial portal blood. However, the probable existence of other PRL-inhibiting factors as well as PRL-releasing factors opens to question the role of dopamine in the dynamic regulation of PRL secretion. We investigated this question in the present study by measuring dopamine concentrations in hypophysial stalk blood of the rat during the surgess of PRL secretion induced by cervical stimulation. Urethane anesthesia, necessary for the surgery attendant to stalk blood collection, did not suppress the surge of PRL secretion induced by cervical stimulation 16-24 h previously. Increases in plasma PRL levels during such surges were 4- to 5-fold above baseline. Dopamine concentrations in hypophysial stalk plasma were 36% lower in cervically stimulated than in control rats during the diurnal and nocturnal PRL surges. However, dopamine levels were not different during the interval between the surges, a time at which PRL levels are similar in stimulated and control rats. To determine if the observed 36% decrease in dopamine levels might account for the associated 4- to 5-fold rise in PRL levels during surges, we treated rats with alpha-methyl-p-tyrosine to block endogenous dopamine secretion and then infused dopamine at various rates to achieve plasma dopamine concentrations throughout the physiological range. These dopamine levels significantly but incompletely suppressed PRL levels, and a 36% decrease in administered dopamine was associated with only an approximate 1.5-fold increase in plasma PRL levels. Thus, it is unlikely that changes in dopamine secretion alone can account for the increased release of PRL engendered by cervical stimulation.

Animals↗

Immunoreactive LH-like substances in serum of hypophysectomized and prepubertal monkeys: inactive in an in vitro LH bioassay.

Serum LH levels in rhesus monkeys are commonly measured by a radioimmunoassay (RIA) utilizing ovine LH as the radioligand and a novel antiserum to ovine LH. Although meeting most criteria of validity, this RIA cross-reacts with serum from demonstrably hypophysectomized monkeys as well as serum from pre-pubertal monkeys. We have utilized the recently developed rat interstitial cell-testosterone assay (RICT) for measurement of serum LH in rhesus monkeys during various endocrine states and have compared the results with those obtained by RIA. The RICT in vitro bioassay was as sensitive, precise, and accurate as the RIA. Partially purified pituitary monkey LH preparations, varying by as much as 100-fold in purity, had similar potency estimates by both assays. The expected biphasic pattern of serum LH levels during the menstrual cycle as well as the usual increase in serum LH levels after ovariectomy was observed with both assays. In each case, however, basal serum LH levels were overestimated by the RIA and peak serum LH levels were underestimated by the RIA as compared to results obtained by the RICT bioassay. The most striking differences between the two assays were observed with serum from hypophysectomized and prepubertal monkeys. Whereas LH-like activity in such samples was high when measured by the RIA, it was undetectable by the RICT bioassay. The ratios of serum LH (RIA/RICT) varied from greater than 7.2 to greater than 17.4 in such sera. These results demonstrate the serious limitations of the ovine LH RIA for measurement of serum LH in rhesus monkeys. It appears that the RICT bioassay may be a suitable alternative method, especially in circumstances other than the menstrual cycle and after ovariectomy.

Animals↗

Pain relief in metastatic cancer other than breast and prostate gland following transsphenoidal hypophysectomy. A preliminary report.

Hypophysectomy was performed in six patients with advanced carcinoma other than from breast and prostate gland to alleviate pain. Two patients received significant and lasting relief of pain; one achieved relief but died from progression of disease 5 weeks after surgery; one patient, initially relieved, had recurrence of pain 3 months later; one had about 50% relief; and one received no benefit. Possible mechanisms for pain relief include changes in pituitary hormones, prostaglandins, and the newly isolated brain peptides, alpha and beta endorphin. These preliminary observations will require further critical evaluation in a larger series to determine the effectiveness of hypophysectomy in relieving pain in cancer other than from the breast and prostate. The results, nevertheless, do imply that a different approach to pain, namely endocrine manipulation, may be beneficial in certain cancer patients.

Adult↗

Transoral, transsphenoidal microsurgical exposure of the pituitary gland and infundibulum in the rhesus monkey. Description of operative technique.

A transoral, transsphenoidal microsurgical technique for exposing the pituitary stalk and gland of the rhesus monkey is described and illustrated. The technique has proved to be a safe and practical method for performing a variety of pituitary operations in a total of 37 animals. The procedures have included complete hypophysectomy, posterior lobe resection, pituitary stalk section, collection of portal venous blood, collection of pituitary venous blood, and placement of lessions in the organum vasculosum of the lamina terminalis.

Animals↗

A "critical period" for cervically-stimulated prolactin relase.

To investigate the role of ovarian steroids in the initiation and maintenance of the prolactin surges typical of pseudopregnancy in the rat, the pattern of plasma prolactin concentrations resulting from cervical stimulation of long-term ovariectomized rats was determined. Cervical stimulation of rats, ovariectomized 2-4 weeks previously, at 1900 h (lights on 0600-1800 h) resulted in a surge of prolactin which was initiated 4-6 h later and which was similar in timing and duration to the nocturnal prolactin surge of intact, pseudopregnant rats. Daily prolactin surges continued for 6 days but declined thereafter. Because plasma progesterone levels were elevated significantly after cervical stimulation, the experiment was repeated iin adrenalectomized-ovariectomized rats. Prolactin surges were still observed, demonstrating that ovarian and adrenal steroids are required neither for initiation nor maintenance of prolactin surges after cervical stimulation. Cervical stimulation at different times of the day (1900 h, 2400 h or 0400 h) always resulted in a surge of prolactin which peaked at 0300-0700 h. The latency from cervical stimulation in the peak of the prolactin surge was 8 h for the 1900 h group, 5 h for the 2400 h group, and 3 h for the 0400 h group. Thus, the appearance of prolactin surges is related to the time of day rather than to the time cervical stimulation is applied, demonstrating the existence of a "critical period" for cervically-induced prolactin release.

Adrenalectomy↗

Termination at midpregnancy of the two daily surges of plasma prolactin initiated by mating in the rat.

The pattern of plasma prolactin following uterine cervical stimulation consists of two surges each day, one nocturnal, occurring between 0100-0900 h (lights on 0600-1800 h), and one diurnal, occurring between 1500-2100 h. This pattern of prolactin continued throughout pseudopregnancy; the last surge was observed on the morning of day 11 (day 1 was taken as the first day of diestrus of pregnancy or pseudopregnancy). Prolactin levels remained low thereafter until the spontaneous proestrous surge on the afternoon of day 12, signalling the onset of a new estrous cycle. In contrast, the two daily prolactin surges did not continue throughout pregnancy, and in fact, were terminated sooner in pregnant animals than in pseudopregnant animals. The last diurnal surge was observed on day 8 while the last nocturnal surge was observed on day 10. The early termination of prolactin surges during pregnancy correlated with the increased secretion of rat placental lactogen. However, placental extracts obtained from day 11 of pregnancy and injected in large doses failed to inhibit prolactin surges in pseudopregnant animals. Prolactin surges also continued for a longer period of time in pseudopregnant rats bearing decidualized uteri than in pregnant animals. Thus, the two major components of pregnancy that differed from pseudopregnancy, that is, the presence of rat placental lactogen or decidual tissue, did not appear to account for the early termination of prolactin surges during pregnancy.

Animals↗