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Biomedical subjects

P D Woolf

Publications and source records attributed to P D Woolf.

At least 55 records · Page 3Linked to original sources
PubMed1985

Prolactin metabolic clearance and resistance to dopaminergic suppression in acute uremia.

A nephrectomized rat model was developed to examine PRL resistance to dopaminergic suppression, which is frequently present in humans with renal insufficiency. The MCR and the response of PRL to a dopamine (DA) infusion (0.4 microgram/kg . min) were measured in 24-h totally nephrectomized (TN) and sham-nephrectomized (SN) rats concurrently treated with alpha-methyl-p-tyrosine (AMPT), an inhibitor of DA synthesis. TN rats became significantly hyperprolactinemic within 1 day [36.2 +/- 7.1 vs. 18.5 +/- 2.5 (+/- SE) ng/ml; P less than 0.05]. SN and TN rats responded to AMPT with significant and sustained 3- and 5.5-fold increases in PRL, which DA reduced by 85% and 24%, respectively. Total nephrectomy decreased the PRL MCR by 58% (TN, 0.51 +/- 0.03; SN, 1.22 +/- 0.13 ml/min; P less than 0.001) and significantly increased the PRL secretion rate (TN, 79 +/- 10; SN, 37 +/- 8 ng/min; P less than 0.01). In the absence of DA infusion, AMPT reduced plasma DA to undetectable levels, while the median eminence DA contents in TN and SN rats were reduced to similar levels. Our data suggest that the totally nephrectomized rat is a suitable model to study PRL resistance to dopaminergic suppression, and that because DA does not cross the blood-brain barrier, the defect in uremia probably occurs at the level of the lactotroph.

Acute Disease↗
PubMed1985

Transient hypogonadotropic hypogonadism caused by critical illness.

The effects of acute severe illness on pituitary-gonadal function were determined in 35 men and 19 women, including 12 who were postmenopausal. Seventeen men and 5 women had traumatic brain injury which resulted in coma. Twelve postmenopausal and 2 premenopausal women had intracranial vascular accidents. Eleven men had myocardial infarctions, while 7 men underwent elective surgery. Serial plasma samples were examined for testosterone (men), percentage of ultrafiltrable testosterone (men), estradiol (women), sex hormone-binding globulin, LH, and FSH. In men, mean testosterone levels fell by 271 +/- 72 (+/- SE), 202 +/- 63 and 195 +/- 75 ng/dl within 24 h of brain injury, myocardial infarction, or elective surgery, representing decreases of 55%, 43%, and 58%. Further declines occurred in the first and third groups to mean nadirs of 93 +/- 16 and 117 +/- 5 ng/dl, respectively. During recovery of neurological function there was no correlation between the testosterone level and the degree of neurological impairment; testosterone levels eventually returned to normal (627 +/- 77 ng/ml). The percentage of ultrafiltrable testosterone and sex hormone-binding globulin did not change in any group. Although significant decreases in mean immunoreactive LH and FSH levels were found after head trauma, and decreases in FSH were found in the men after surgery, these changes occurred after the decline in testosterone. Despite the fall in basal gonadotropin levels in the head trauma group, there were no significant differences in the gonadotropin responses to GnRH (100 micrograms) in 4 patients during their acute illness or recovery. LH, FSH, and estradiol levels in the premenopausal women were significantly lower on the second day of brain injury (LH, 10.3 +/- 4.7 vs. 3.5 +/- 0.6 mIU/ml; FSH, 3.8 +/- 1.9 vs. 1.4 +/- 0.8 mIU/ml, estradiol, 200 +/- 41 vs. 102 +/- 16 pg/ml) and remained suppressed for 7 days. Gonadotropin levels also fell in the postmenopausal women within 24 h; reductions in LH of 74% and in FSH of 62% were present by day 7 of study. We conclude that both men and women who are critically ill uniformly develop temporary hypogonadotropic gonadal insufficiency regardless of their illness. In men, it is manifested by low testosterone levels, while a comparable decrease in estradiol is present in women. The low testosterone concentrations are not due to reduced sex hormone-binding capacity. Based upon our data in postmenopausal women, hypogonadotropism also occurs in the presence of nonfunctioning gonads. Although our studies do not completely establish the pathophysiology of this disorder, they suggest a suprapituitary origin.

Adolescent↗
PubMed1984

Parathyroid hyperplasia and carcinoma within one gland.

A 47-year-old Scottish woman vacationing in the United States presented with a serum calcium level greater than 20 mg/dl and a parathyroid hormone level 16 times greater than normal after a one-week history of severe vomiting and unrelenting abdominal pain. Surgical exploration of the thymus revealed the very rare association of a large (7 by 4 by 0.8 cm) parathyroid carcinoma adjacent to apparently normal parathyroid tissue, separated by a thin fibrous band. Two other hyperplastic and one normal parathyroid glands were also identified. Postoperatively, the patient became hypocalcemic and, for the past nine months, has received maintenance 1-alpha-hydroxycholecalciferol therapy (1 microgram per day) with normal calcium and barely detectable parathyroid hormone levels.

Carcinoma↗
PubMed1984

Determination of free thyroxin in serum by ultrafiltration: validation of a method and preliminary results.

We describe the determination of concentrations of free thyroxin in serum by ultrafiltration based on the Amicon micropartition system. The assay is straightforward and requires about 4 h for 25 samples. Our results demonstrate a correlation coefficient of 0.81 compared with equilibrium dialysis, and of 0.88 compared with radioimmunoassay. For sera from 49 normal, 25 hyperthyroid, 24 hypothyroid, 50 euthyroid sick, and 13 pregnant subjects, the means (and SD) were respectively: 19.3 (4.9), 40.1 (13.6), 5.0 (2.9), 25.9 (10.5), and 16.1 (3.2) ng/L. The interassay CV was 9.9% and the intra-assay CV 7.2%. We conclude that this procedure is useful in the diagnosis of thyroid disease and offers advantages of simplicity, rapidity, and economy.

Dialysis↗
PubMed1983

Plasma ACTH levels in depression before and after recovery: relationship to the dexamethasone suppression test.

Sixteen patients with major depressive disorder who were nonsuppressors on the dexamethasone suppression test (DST) on hospital admission were studied for plasma levels of adrenocorticotropic hormone (ACTH). Eight patients reverted to normal suppression with clinical recovery, while eight remained nonsuppressors. There was a significant reduction of ACTH levels in those who normalized on their DST, while ACTH levels remained high in the group that continued to be nonsuppressors. The results favored the hypothesis that dexamethasone nonsuppression in depression is mediated by high ACTH levels.

Adrenocorticotropic Hormone↗
PubMed1983

Plasma ACTH levels in primary depression: relationship to the 24-hour dexamethasone suppression test.

The failure of adequate cortisol suppression after 1 mg dexamethasone in 50% of patients with endogenous depression has been attributed to abnormal hypothalamic-pituitary-adrenal axis regulation, resulting in high levels of adrenocorticotropic hormone (ACTH). Because studies of plasma ACTH have been conflicting, we studied plasma ACTH levels during the 24-hour dexamethasone suppression test in a homogeneous group of 29 hospitalized patients with primary endogenous depression and 19 normal volunteers. No differences were found in ACTH levels among normal volunteers, depressed cortisol suppressors, and depressed cortisol nonsuppressors at either 4 p.m. or 11 p.m.

Adrenocorticotropic Hormone↗
PubMed1983

Evaluation of the dopamine response to stress in man.

Because the role of circulating dopamine (DA) in the sympathetic nervous system response to stress remains unclear, alterations in peripheral DA concentrations were determined in healthy volunteers after assuming upright posture (n = 6), hand immersion in ice water (cold pressor, n = 6), and insulin-induced hypoglycemia (n = 11) and in 17 comatose patients with severe brain injury (11 head trauma and 6 intracranial hemorrhage). Changes in DA levels were compared to increases in epinephrine (E) and norepinephrine (NE), all of which were measured by the radioenzymatic technique. The minimum sensitivities were 42, 22, and 38 pg/ml, respectively. In 19 normal men and 22 women, basal DA levels were below assay sensitivity in 31 and were 85 +/- 7 (+/- SE) pg/ml in the remainder. Plasma E was measurable in all but 7 subjects, with a mean concentration of 41 +/- 4 pg/ml. NE levels were 201 +/- 17 pg/ml in 30 of the 31 subjects in whom it was detectable. There was no sex difference for any of the catecholamines. Upon standing, neither DA nor E changed significantly, but NE, increased by 176 +/- 40 pg/ml (P less than 0.0025). There were no significant changes in DA or E concentrations during the cold pressor test, while NE increased by 212 +/- 66 pg/ml (P less than 0.025). Compared to the E (1044 +/- 356 pg/ml; P less than 0.02) and NE (233 +/- 62 pg/ml; P less than 0.005) increments after hypoglycemia, the maximal DA increment, although significant (62 +/- 22 pg/ml; P less than 0.025), was less than those of the other catecholamines. DA levels were measurable in only 7 of 40 samples from 17 brain-injured patients and was 72 +/- 13 pg/ml in the remainder. However, E and NE levels were detectable in 79% of the samples and were significantly greater than normal (125.6 +/- 14 and 594 +/- 59 pg/ml; P less than 0.001, respectively). It is concluded that basal DA levels are generally below the assay limits of detectability. Furthermore, measurement of circulating levels suggests that DA participates in the general sympathetic response only when the adrenal component is maximally activated.

Adolescent↗
PubMed1983

Hyperprolactinemia and delayed puberty: a report of three cases and their response to therapy.

Delayed puberty occurred in three patients (aged 15 to 22 years) with elevated prolactin levels. Despite the varying etiologies, their clinical presentations were marked by absence of galactorrhea, prepubertal genitalia (2/3), and short stature (1/3). Except for hyperprolactinemia, endocrinologic evaluation was normal in two patients. Bromocriptine restored prolactin levels to normal in all three patients, two of whom had prior transsphenoidal surgery, and resulted in initiation of menses in one girl and pubertal development in both boys. The 22-year-old male patient with the empty sella syndrome has progressed through puberty after the addition of oral testosterone.

Adolescent↗
PubMed1982

Dopamine does not affect parathyroid function in man.

There is conflicting evidence for a role of dopamine (DA) in modulating parathyroid gland function. DA stimulates parathormone (PTH) secretion in cattle in vivo and in vitro, but is without effect on dispersed human parathyroid cells from adenomatous and hyperplastic tissue. Therefore, we studied the PTH response to a 30-min infusion of DA (4 micrograms/kg . min) in five normal male volunteers. There was no change in the levels of PTH, as measured by RIA, although this infusion rate was effective in lowering PRL levels. During the infusion period, total calcium levels remained unchanged. We conclude that, unlike cattle, the parathyroid gland in humans is unresponsive to DA. Thus, the regulation of PTH secretion by biogenic amines has important species variation.

Adult↗
PubMed1982

Concurrent production of adrenocorticotropin and prolactin from two distinct cell lines in a single pituitary adenoma: a detailed immunohistochemical analysis.

A pituitary tumor from a patient with severe Cushing's disease and marked hyperprolactinemia was extensively studied by immunohistochemical techniques. Tissues from two separate areas of the adenoma were found to contain similar cell proportions of PRL as well as ACTH and related peptides (beta-lipotropin, beta-endorphin, and alpha MSH). The tumor was composed of approximately 70% immunoreactive PRL cells and 5% ACTH-containing cells. Double immunostaining revealed that PRL or ACTH and related peptides were found in two distinct populations of tumor cells. These results document for the first time inappropriate synthesis and secretion of an unusual combination of pituitary hormones from a mixed pituitary adenoma.

Adenoma↗
PubMed1981

Resumption of prolactin secretion after dopaminergic inhibition: differential effects of dopamine and its agonists.

The recovery of prolactin (PRL) secretion following dopaminergic inhibition was studied in vitro using pituitary monolayer cultures. PRL secretion over 4 h was inhibited comparably by 10(-6) M dopamine (DA), 10(-7) M apomorphine (APO), and 10(-10) M bromocriptine (45%, 42%, 51%, respectively) with reciprocal increases in intracellular hormone content. After drug removal, the PRL secretion rate in the cultures that had been treated with DA was 208% of the control cultures by the 2nd h but returned to control values by 4 h, whereas the secretion rate after APO was 131-142% of control throughout the 4-h recovery period. In contrast, PRL secretion remained significantly less than control 20 h after the removal of bromocriptine. Although haloperidol (10(-7) M) prevented the inhibitory action of bromocriptine when added simultaneously, the addition of haloperidol did not restore PRL secretion when added in the posttreatment period. Thus, DA and APO inhibition of PRL release is readily reversible and is followed by early PRL hypersecretion. However, bromocriptine's effects are sustained and once started are not reversed by DA antagonists.

Animals↗
PubMed1981

Dopaminergic stimulation and inhibition of growth hormone secretion in normal man: studies of the pharmacologic specificity.

We have previously reported that dopamine (DA) stimulates basal GH secretion, but blunts the response to hypoglycemia. Because the pharmacological specificity of these dual actions has never been determined, a four-part study was undertaken. Before the administration of regular insulin (0.1 U/kg), male subjects received saline, DA or the DA agonist bromocriptine either alone or during dopaminergic blockade with metoclopramide. DA and bromocriptine increased GH levels comparably, and pretreatment with metoclopramide abolished this response [control, 2.9 +/- 0.7 (+/- SE); DA, 12.8 +/- 3.2 (P less than 0.01); bromocriptine, 13.0 +/- 3.4 (P less than 0.05); bromocriptine plus metoclopramide, 4.8 +/- 1.4 ng/ml (NS compared to control; P less than 0.05 compared to bromocriptine)]. Both DA and bromocriptine significantly inhibited the GH response to hypoglycemia [peak increment: control, 35.2 +/- 4.8; DA, 7.5 +/- 1.8 (P less than 0.001); bromocriptine, 13.7 +/- 3.2 ng/ml (P less than 0.05)], while pretreatment with metoclopramide restored GH secretion to normal (24.5 +/- 6.8; NS compared to control). Similar results were obtained comparing the mean GH peaks and areas under the curve. While there was no correlation in the hypoglycemic GH responses between the control and dopaminergic studies, the blunting effects of dopamine and bromocriptine were highly correlated (r = 0.93; P less than 0.001). Consequently, under basal conditions, DA and bromocriptine stimulate GH to a similar degree and diminish the GH response to hypoglycemia comparably. Pretreatment with the DA antagonist metoclopramide returns GH secretion to normal by preventing the increase after bromocriptine and restoring the hypoglycemia-medicated rise. Therefore, the dual actions of DA on GH secretion are mediated by a dopaminergic mechanism, since they are mirrored by a specific DA agonist and prevented by a DA antagonist.

Blood Glucose↗