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Biomedical subjects

K Hall

Publications and source records attributed to K Hall.

At least 253 records · Page 14Linked to original sources
PubMed1984

Somatomedin levels in cerebrospinal fluid from adults with pituitary disorders.

Somatomedin levels in cerebrospinal fluid (CSF) were determined in patients with acromegaly, pituitary deficiency, prolactinoma, and Cushing's disease by radioimmunoassay (RIA) for insulin-like growth factor 1 (IGF-1) and for IGF-2 as well as a radioreceptor assay (RRA) with adult human brain plasma membranes and IGF-2 as ligand. The mean value of RIA-IGF-2 (31 +/- 1.6 ng/ml) predominated over that of RIA-IGF-1 (5.8 +/- 0.3 ng/ml), but 10 times higher levels were found by RRA-IGF-2. Patients with acromegaly were not found to have higher values than those with GH deficiency even after corrections were made for possible leakage across the blood-CSF barrier. No correlations were found between CSF somatomedin levels determined by different techniques and immunoreactive IGF-1 or GH in the peripheral circulation except for a positive correlation between CSF RIA-IGF-2 and serum IGF-1 in patients with acromegaly. These findings suggest that somatomedins in CSF consist primarily of IGF-2-like peptides which are derived from production within the central nervous system or pituitary gland rather than from transport across the blood-CSF barrier.

Acromegaly↗
PubMed1984

Cross-reaction of serum somatomedin-binding protein in a radioimmunoassay developed for somatomedin-binding protein isolated from human amniotic fluid.

A radioimmunoassay was developed for somatomedin-binding protein isolated from human amniotic fluid. The mean level in amniotic samples from 20-22 week of gestation was high, 51 micrograms/ml. Human serum and serum fraction gave dose-response curves superimposable on that for the pure amniotic binding protein. Gel chromatography of serum at neutral pH disclosed immunoreactive binding protein only in fractions with a molecular size of 35 000 corresponding to elution volume for the low molecular form somatomedin-binding protein. The mean levels (mean and range) of immunoreactive somatomedin-binding protein in cord blood (191 ng/ml, 55-1698 ng/ml) and in diabetic patients with uraemia (97 and 51-174 ng/ml) were 5- to 10-fold elevated above those of healthy adults (23 and 18-36 ng/ml). In acromegaly the levels decreased with increasing GH production (r = -0.77; P less than 0.005). In adult patients with GH deficiency the levels were 2-fold elevated in comparison with healthy subjects. Apart from patients with uraemia a negative correlation was found in adults between the levels of immunoreactive binding protein and immunoreactive IGF-I which reflect the GH production (r = -0.81, P less than 0.001).

Acromegaly↗
PubMed1983

Characterization of insulin binding to the erythroleukemia cell line K 562.

The K 562 is a transformed human erythroid stemcell and is used as a target cell for NK-T-cells. In this study the presence of insulin receptors in K 562 is established. The best binding and negative cooperativity was found in the two Hepes containing buffers whereas no cooperativity was obtained in the Krebs-Ringer buffer. The calculated affinity constants and receptor number per cell varied according to the buffer. Preincubation with insulin caused a down-regulation of the insulin binding capacity. 10 ng/ml caused a lowering of the affinity, with an unchanged number of receptors. 100 ng/ml caused a decrease in receptor number with unchanged affinity. These results were found in both Hepes and Krebs-Ringer phosphate buffer. IGF-I shows cross-reactivity with the insulin receptor, with a potency of 12 and 100 times less than insulin in Krebs-Ringer phosphate buffer and G-buffer respectively. However, no specific IGF-I receptors were found. The presence of receptors on K 562 cells suggests a biological role for insulin. The different results in the different buffers, indicate that a buffer containing Hepes and/or Tris, is required to expose negative cooperativity and make the receptors more accessible to insulin.

Binding, Competitive↗
PubMed1983

Subnanogram determination of fluphenazine in human plasma by gas chromatography mass spectrometry.

A new gas chromatographic mass spectrometric procedure for the quantitation of fluphenazine in plasma is described. The method relies on the selected ion monitoring of fluphenazine (m/z 406.1563) and perphenazine (m/z 372.1299), the internal standard, after extraction from plasma with 5% isopropanol in n-pentane. Interferences by plasma constituents such as cholesterol are avoided by including an n-hexane wash. This wash step reduced the recovery of fluphenazine and to a greater extent perphenazine, however, it yielded an organic solution relatively free of any peaks with interfering ions. Prior to gas chromatographic mass spectrometric analysis the silyl derivatives of fluphenazine and perphenazine are prepared using N,O-bis(trimethyl-silyl)acetamide. This procedure allows for the quantitation of as low as 78 pg of fluphenazine per ml of plasma using 2.0 ml plasma aliquots with a coefficient of variation of 4.6%. The high specificity and sensitivity demonstrated by this method allows for the first time the monitoring of plasma concentrations of fluphenazine up to 32 h following a single oral dose of 5 mg of the drug.

Fluphenazine↗
PubMed1983

Kinetics of oral fluphenazine disposition in humans by GC-MS.

The disposition of fluphenazine was investigated in six healthy volunteers following oral administration (5 mg). Using a sensitive and specific GC-MS procedure plasma fluphenazine concentrations were measured up until 32 h after drug administration. Peak plasma concentrations varied widely (range: 0.26-1.06 ng/ml) and were observed at 2.8 +/- 0.5 h following fluphenazine administration. The apparent terminal elimination half-life of fluphenazine was 33.1 +/- 8.1 h. The area under the plasma concentration-time curve differed widely between subjects (range: 7.1-28.6 ng/ml h) suggesting large interindividual differences in the extent of fluphenazine presystemic elimination.

Administration, Oral↗
PubMed1983

Hyperprolactinemia. Long-term effects of bromocriptine.

Patients with hyperprolactinemia may be managed by pituitary surgery or irradiation, bromocriptine treatment, or a combination of these methods, and some patients remain untreated. Little is known of the long-term consequences of some of these therapeutic regimens. Forty-six hyperprolactinemic patients (40 female and six male) managed solely with bromocriptine or no treatment over a period of 12 months to six years were therefore evaluated in this study. Nine patients with radiologically normal pituitary fossae were untreated and 10 received bromocriptine, 7.5 to 10 mg daily, while 20 patients with radiologic evidence of a pituitary tumor were treated with bromocriptine, generally 10 to 20 mg daily. Patients were assessed clinically, biochemically, and radiologically before treatment and at least six weeks after discontinuation of therapy. A further seven patients were similarly assessed before and after eight bromocriptine-induced pregnancies. Symptoms persisted in the untreated group of nine patients, although menstruation returned in four of the females with previous amenorrhea; serum prolactin levels remained elevated, other pituitary function did not change, and pituitary fossae remained normal radiologically. In all patients treated with bromocriptine, symptoms improved irrespective of radiologic findings on the pituitary, and were abolished in 67 percent during treatment associated with a decrease in serum prolactin levels in all, and a return of levels to within normal limits in 80 percent of patients. Persistent side effects were usually dose-related, but remained troublesome in 13 percent. Bromocriptine-induced tumor regression was evident radiologically in all patients with suprasellar tumor tissue and in some with purely intrasellar adenomas. This effect occurred rapidly and persisted or increased throughout follow-up. On discontinuation of treatment, prolactin levels remained significantly lower than before therapy (mean 2,934 versus 5,052 mU/liter, p less than 0.05) but were within the normal range in only two patients. Other pituitary function was unaltered, or improved in some patients with definite tumors. Bromocriptine-induced pregnancy produced no permanent change in clinical, biochemical, or radiologic status. Long-term bromocriptine treatment for hyperprolactinemia is thus highly effective in alleviating symptoms and suppressing prolactin secretion, and induces persistent tumor regression on treatment without deterioration of other pituitary function in patients with macroadenomas. On discontinuation of therapy, however, hyperprolactinemia usually recurs, and treatment may therefore need to be continued for years.

Adult↗
PubMed1983

Ontogenesis of somatomedin and insulin receptors in the human fetus.

This study examines the ontogenesis of somatomedin and insulin receptors in man. Particulate plasma membranes were prepared by ultracentrifugation from various tissues removed from fetuses after abortion and classified as less than 17, 17-25, and greater than 25 cm in length. The binding of iodinated insulinlike growth factors 1 (IGF-1) and 2 (IGF-2), somatomedin A (SMA), multiplication-stimulating activity (MSA), and insulin was examined at the different ages. In the liver, cross-reaction studies revealed separate insulin and IGF-2 receptors. The Scatchard plots of insulin binding to liver membranes were curvilinear and showed an increase in the concentration of insulin receptors with advancing age. A single IGF-2 receptor was found on liver and no alteration was observed during development. The brain contained a lower concentration of insulin receptors. A change in the brain receptors for somatomedins occurred during development. Early in gestation, a high concentration of a low-affinity IGF-1 receptor was found. After approximately the 17th wk of gestation a higher affinity IGF-1 receptor appeared, which then increased in concentration. Cross-reaction studies also revealed changes in the specificity of these receptors during development. In the youngest fetal group IGF-2 was preferentially bound. Around midgestation a separate IGF-1 receptor, indicated by the preferential displacement of iodinated IGF-1 by IGF-1, appeared. In contrast, iodinated IGF-2 bound to a receptor where IGF-1 and IGF-2 were equipotent.

Brain↗
PubMed1983

Effects of hysterectomy and uterine extracts on growth hormone, somatomedin, prolactin, thyrotrophin and thyroid hormones in adult rats.

Plasma concentrations and anterior pituitary content of growth hormone (rGH), thyroid stimulating hormone (rTSH), and rat prolactin (rPrl) as well as the plasma concentrations of triiodothyronine (T3), thyroxine (T4) and somatomedin A (SM-A) have been determined in intact, castrated or hysterectomized adult rats with and without treatment with steroid-free, crude uterine extracts. Hysterectomy caused a significant increase in the plasma GH but decrease in the plasma TSH concentrations. Injection of crude, steroid-free uterine extracts for 14 days had the following effects: decreased plasma GH concentration of intact rat and anterior pituitary GH content of both intact and castrated animals; increased plasma TSH and T3 concentrations above the ovariectomized control; decreased pituitary content of prolactin in castrated rats. The plasma levels of immunoreactive somatomedins A were negatively correlated to the plasma GH concentrations but positively correlated to the body weight. It was concluded that the uterus is not only a target for different endocrine influences but contains biologically active, non-steroidal substances which have a complex effect on the endocrine system of adult, female rats.

Animals↗
PubMed1983

Estrogen treatment of tall girls: risk of thrombosis?

In 34 girls who were treated with large doses of ethinylestradiol because of expected excessive tall stature, antithrombin activity in the blood was followed before, during, and after treatment. All girls showed lower levels of antithrombin during treatment than before or after estrogen administration; the mean concentration during treatment was at or below the lower limit of control values (-2 SD). In three girls, the antithrombin levels were so low that the medication was withdrawn. There was no difference between the mean levels of antithrombin activity in the three groups treated with 0.25, 0.50, or 1.0 mg of ethinylestradiol. Deficiency of antithrombin is known to be associated with an increased risk of thrombosis. Therefore, antithrombin concentrations in blood should be determined before and during treatment with large doses of estrogens.

Adolescent↗
PubMed1982

Evidence for the presence of specific receptors for insulin-like growth factors 1 (IGE-1) and 2 (IGF-2) and insulin throughout the adult human brain.

The present study examines adult human brain tissue for the presence of receptors for insulin-like growth factors (IGFs) 1 and 2 and insulin. Binding sites for all hormones were widely distributed throughout the brain removed at autopsy, with the highest specific binding being found in the various cortical regions. Cross-reaction studies performed on frontal lobe biopsy material indicated specific binding sites for IGF-1 and insulin whereas iodinated IGF-2 was equally displaced by IGF-1 and IGF-2, suggesting the presence of an additional IGF-2-like binding site in the adult brain.

Aged↗
PubMed1982

Gas chromatographic--mass spectrometric procedure for the quantitation of chlorpromazine in plasma and its comparison with a new high-performance liquid chromatographic assay with electrochemical detection.

A gas chromatographic--mass spectrometric assay using selected ion monitoring is compared with a high-performance liquid chromatographic assay using an electrochemical detector for single-dose studies of the psychotherapeutic phenothiazine drug chlorpromazine. Measurements were made after extraction of chlorpromazine and the internal standard, prochlorperazine, from basified plasma with an isopropanol--pentane solvent mixture. Following evaporation of the organic solvents the residue was reconstituted in a small volume of methanol and subjected to gas chromatographic--mass spectrometric selected ion detection. The residual sample was then evaporated and made up in a larger volume of acetonitrile and analyzed by high-performance liquid chromatography using an electrochemical detector. These specific methods display excellent correlation for plasma concentration determinations in the range of 0.25-10 ng ml-1 and will allow for the study of the pharmacokinetics of chlorpromazine following single low doses of the drug.

Chlorpromazine↗
PubMed1982

Reduction in size of prolactin-secreting tumours in men treated with pergolide.

The effect of pergolide mesylate was studied in two previously untreated men with large prolactinomas and exceptionally high prolactin concentrations. The study was designed to determine whether pergolide would be effective in alleviating symptoms, correcting hormonal abnormalities and shrinking the tumour. Starting with 50 micrograms daily the dose of pergolide was slowly increased over 10 weeks to 1 mg once daily, when repeat assessment was performed. Both patients reported complete relief of symptoms, with no side effects. Serum prolactin concentration was suppressed to normal in both subjects, and evidence to suggest tumour shrinkage was observed. Pergolide appears to be effective treatment for men with large prolactinomas.

Antineoplastic Agents↗