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Biomedical subjects

K Hall

Publications and source records attributed to K Hall.

At least 127 records · Page 7Linked to original sources

Effects of recombinant human insulin-like growth factor I administration in adults with growth hormone deficiency.

Recombinant human insulin-like growth factor I (IGF-I), 40 micrograms/kg/body weight, was administered subcutaneously at 08.00 hours to six adult patients with growth hormone deficiency (GHD). The mean maximal IGF-I concentrations were found 2-6 hours after injection. Concentrations then gradually declined, though mean values were still above basal 24 hours after the injection. Only one patient maintained IGF-I levels above the lower normal range throughout 24 hours. There was a significant decrease in mean IGF-II concentrations when measured 4 and 24 hours after injection of IGF-I. The diurnal variations of insulin and IGF binding protein-1 were preserved. There were no side-effects, and blood glucose remained normal. These results show that in patients with low IGF-I levels resulting from GHD, it is necessary to administer IGF-I at intervals of less than 24 hours to obtain IGF-I levels that are within the normal range.

Adult↗

Growth hormone insensitivity syndromes: a preliminary report on changes in insulin-like growth factors and their binding proteins during treatment with recombinant insulin-like growth factor I. Kabi Pharmacia Study Group on Insulin-like Growth Factor I Treatment in Growth Hormone Insensitivity Syndromes.

Serum levels of insulin-like growth factor (IGF) binding proteins (IGFBPs) 1, 2 and 3 were studied by radioimmunoassay in 29 patients with growth hormone (GH) insensitivity syndromes (GHIS) before and during treatment with IGF-I. As in normal subjects, there was a highly significant correlation between IGFs and IGFBP-3 but not between IGFs and the other binding proteins, though IGFBP-3 represented only about one-third of the total IGFBP concentration. In 6 patients with GH deficiency and in 5 patients with GHIS, the pharmacokinetic profile of IGF-I after a single injection was strongly dependent on the IGFBP-3 concentration. A slight but significant increase in IGFBP-3 was observed coincident with the IGF-I peak, whereas IGFBP-2 increased after a delay of about 10 hours. In the patients with GHIS, chronic IGF-I treatment, with twice-daily injections for 6 months, caused a significant steady decline of IGF-II and an increase in IGFBP-2, but had no effect on IGFBP-1 and IGFBP-3 levels. During IGF-I treatment, an inverse relationship between baseline IGF-I and GH levels was observed. The data suggest that total IGF-I and IGF-II serum levels are determined mainly by IGFBP-3, even in extreme situations such as GHIS, while other IGFBPs are less important. The IGFBP-3 concentration seems to be a major regulator of the pharmacokinetics of exogenous IGF-I, which, in turn, influences IGFBP-3 levels. This effect of IGF-I on IGFBP-3 is not through induction of IGFBP-3 synthesis, but possibly by reduction of IGFBP-3 clearance.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Dissociative disorders in psychiatric inpatients.

OBJECTIVE: This study attempted to determine 1) the prevalence of dissociative disorders in psychiatric inpatients, 2) the degree of reported childhood trauma in patients with dissociative disorders, and 3) the degree to which dissociative experiences are recognized in psychiatric patients. METHOD: A total of 110 patients consecutively admitted to a state psychiatric hospital were given the Dissociative Experiences Scale. Patients who scored above 25 were matched for age and gender with a group of patients who scored below 5 on the scale. All patients in the two groups were then interviewed in a blind manner, and the Dissociative Disorders Interview Schedule, the Traumatic Antecedent Questionnaire, and the posttraumatic stress disorder (PTSD) module of the Structured Clinical Interview for DSM-III-R, Nonpatient Version, were administered. Chart reviews were also conducted on all patients. RESULTS: Fifteen percent of the psychiatric patients scored above 25 on the Dissociative Experiences Scale; 100% of these patients met DSM-III criteria for a dissociative disorder. These patients had significantly higher rates of major depression, PTSD, substance abuse, and borderline personality than did the comparison patients, and they also reported significantly higher rates of childhood trauma. Chart review data revealed that dissociative symptoms were largely unrecognized. CONCLUSIONS: A high proportion of psychiatric inpatients have significant dissociative pathology, and these symptoms are underrecognized by clinicians. The proper diagnosis of these patients has important implications for their clinical course.

Adolescent↗

Glucagon stimulates insulin-like growth factor binding protein-1 secretion in healthy subjects, patients with pituitary insufficiency, and patients with insulin-dependent diabetes mellitus.

Glucagon (1-1.5 mg) was administrated iv as a bolus dose to healthy individuals (n = 7), patients with GH deficiency (n = 14), and patients with insulin-dependent diabetes mellitus (IDDM; n = 6). Thereafter, blood samples for determination of serum glucose, insulin, insulin-like growth factor-binding protein-1 (IGFBP-1), GH, and insulin-like growth factor-I (IGF-I) concentrations were collected for 180 min. IGFBP-1 concentrations increased significantly in response to glucagon, with maximal values observed at 90 min [in healthy subjects from 36 +/- 6 to 58 +/- 10 micrograms/L (P < 0.05), in GH-deficient patients from 36 +/- 4 to 54 +/- 6 micrograms/L (P < 0.001), and in IDDM patients from 115 +/- 18 to 167 +/- 27 micrograms/L (P < 0.05)]. The IGFBP-1 elevation was delayed in relation to the glucagon-induced increase in glucose and insulin concentrations. When the groups were combined, the individual IGFBP-1 peak value observed at 90 min was inversely correlated to the individual peak value of insulin observed at 15-30 min (r = -0.743; P < 0.001). In GH-deficient patients, serum GH concentrations remained undetectable (< 0.2 micrograms/L), and IGF-I concentrations were unchanged after the glucagon injection. In healthy subjects and IDDM patients, mean GH levels did not change significantly, whereas mean IGF-I concentrations decreased slightly at 30 min. In conclusion, glucagon increased serum IGFBP-1 concentrations in spite of increases in glucose and insulin. These results suggest that glucagon is a stimulator of IGFBP-1.

Adult↗

Clinical features and endocrine status in patients with growth hormone insensitivity (Laron syndrome).

Twenty-seven patients with GH insensitivity were identified from 44 possible cases, using a scoring system based on height standard deviation score (SDS), basal GH, insulin-like growth factor-I (IGF-I), IGF-I response to IGF-I generation test, and GH-binding protein (GH-BP) determinations. The 27 cases were from 8 European countries and Australia. Clinical features were as follows: age 2.8-22.6 yr; 12 male, 15 female, 19 prepubertal. Birth weight was median -0.72 SDS (1.75(-)-3.29) and birth length, median -1.59 SDS (0.63(-)-3.63). Hypoglycemia had been documented in 33% of the cases, and micropenis was present in 58% of the males. At assessment, height was median -6.1 SDS (-3.8(-)-10.2), weight was median -3.2 SDS (-0.1 to -5.2), and percentage weight for height, median 111.3 (72-271). Puberty was absent in 2 boys aged 15 yr and in 3 girls aged 13 yr. Bone age was delayed in 19 of the 27 patients. Endocrine investigations showed basal serum GH median 17 micrograms/L (0.5-79), IGF-I values less than 5th percentile, and all except 2, age less than 8 yr, less than 0.1 percentile for age. Percentage increment of IGF-I during IGF-I generation test (hGH 0.1 U/kg body weight daily x 4) did not exceed twice the intraassay coefficient of variation, being less than 0.1 percentile for age. IGF-II was median 135.0 micrograms/L (62-232), all values being less than 5th percentile for age. Insulin-like growth factor binding protein-3 (IGFBP-3) values were median 0.53 mg/L (0.10-1.17 mg/L), all being less than 5th percentile for age. IGFBP-3 values after hGH remained less than 5th percentile. IGFBP-1 values showed the normal fall with age, some being above the normal range; IGFBP-2 values were normal. There was a positive correlation between height SDS and IGF-II SDS (r = 0.66, P < 0.001) and IGFBP-3 (r = 0.64, P < 0.001). Specific binding of [125I]hGH to GH-BP was undetectable in 18 patients and extremely low (< or = 5.6%) in 2. GH-BP was normal (14.2-45.9% radioactivity) in 7 subjects, all female, demonstrating that normal GH-BP does not exclude GH insensitivity.

Adolescent↗

Insulin-like growth factor binding protein-1 from Hep G2 cells is potently inhibited by the truncated IGF-I analogue des-(1-3) IGF-I.

Des-(1-3) insulin-like growth factor-I (IGF-I) is an IGF analogue lacking aminoacid 1 to 3 which displays reduced binding to insulin-like growth factor binding protein-1 (IGFBP-1). A greater inhibition of immunoreactive IGFBP-1 was obtained with des-(1-3) IGF-I (10 ng/ml) in Hep G2 medium when incubated in Eagle's Modified Essential Medium (EMEM) without phenolred compared to EMEM with phenolred; EMEM without phenolred was chosen for further experiments. Des-(1-3)IGF-I decreases dose dependently the concentration of IGFBP-1, with a maximal effect at 3-10 micrograms/l when incubated for 24 h; 10 micrograms/l of des-(1-3)IGF-I caused a small but significant inhibition of IGFBP-1 after 8 h incubation and this inhibition was 41% and 33% of controls after 14 and 19 h incubation. The relative potencies at 16 h of incubation of IGF-I and insulin in suppressing IGFBP-1 in comparison to des-(1-3)IGF-I were 0.41 (0.25-0.78) and 0.08 (0.01-0.26), respectively. A dose-dependent decrease of IGFBP-1 mRNA to 30% of control was observed after 4 h incubation with 0.1-10 micrograms/l des-(1-3)IGF-I. Changes of glucose concentration (0-20 mmol/l) in the medium did not affect the IGFBP-1 concentration in the medium. In summary: Des-(1-3)IGF-I was tenfold more potent than insulin, and threefold more potent than IGF-I in decreasing IGFBP-1 concentration in medium conditioned by Hep G2 cells.

Analysis of Variance↗

Rapid resolution of visual abnormalities with medical therapy alone in patients with large prolactinomas.

Large prolactin-secreting pituitary adenomas with suprasellar extension are often complicated by visual field defects, for which surgical decompression is the accepted treatment. However, surgical management of large prolactinomas is often not curative. This report describes a group of six unselected male patients who presented with visual field defects and reduced visual acuity due to large pituitary tumours with suprasellar extension. All six patients also had loss of libido and/or impotence. A rapid serum prolactin estimation enabled the diagnosis of prolactinoma to be made, and CT revealed a large pituitary adenoma with suprasellar extension. The patients were treated with bromocriptine, in doses increasing from 2.5 to 20 mg daily, as the sole therapy. Symptoms were relieved and serum prolactin levels were restored to normal or near normal; visual field defects resolved and visual acuity recovered in all patients. A repeat CT showed evidence of tumour shrinkage especially of the suprasellar extension, in all the patients. A diagnosis of prolactinoma should always be considered in a patient with a large pituitary tumour. The clinical history and a rapid prolactin assay will confirm the diagnosis. Treatment with bromocriptine leads to rapid improvement in perimetry and visual acuity as well as tumour shrinkage, obviating the need for pituitary surgery.

Adult↗

Insulin-like growth factor (IGF) I and II and IGF binding protein (IGFBP) 1, 2 and 3 in serum from patients with Cushing's syndrome.

In the present study of twenty-two patients with Cushing's syndrome, serum insulin-like growth factor (IGF)-I concentrations were normal to high with an increased mean IGF-I concentration, 40% above that of healthy subjects of the same age (p < 0.001). Serum IGF-II concentrations were normal. The morning serum IGF binding protein (IGFBP)-1 concentrations were within the range of healthy controls. IGFBP-1 was inversely correlated to the IGF-I concentration (p < 0.001) and to the 24 h urinary cortisol excretion (p < 0.005) with a combined R squared value of 0.58. In contrast to IGFBP-1, serum IGFBP-2 and IGFBP-3 concentrations were elevated by 1.89 +/- 1.78 SD and 0.92 +/- 0.78 SD (mean +/- 2 SD), respectively. Although increased, the serum IGFBP-2 concentration was inversely correlated to the IGF-I concentration (r = -0.67, p < 0.001). Immunoreactive IGFBP-3 was increased in proportion to IGF-I and the molar ratio [IGFBP-3]:[IGF-I] + [IGF-II] was close to unity (1.04 +/- 0.14), as that of healthy subjects. In serum from patients with Cushing's syndrome, with increased immunoreactive IGFBP-3, there was a corresponding increase in intact glycosylated 40-43 kDa IGFBP-3 as determined by Western ligand blotting. Neutral size chromatography of serum from patients with Cushing's syndrome showed that IGF-I and IGFBP-3 immunoreactivity were predominantly found at the elution volume of the ternary 150 kDa IGF-I/IGFBP-3/acid labile subunit complex and a similar pattern was displayed by normal serum.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

A major outbreak of foodborne gastroenteritis among Air Force personnel during Operation Desert Storm.

An outbreak of foodborne gastroenteritis affected 648 United States Air Force personnel stationed in Jeddah, Saudi Arabia during Operation Desert Storm. The implicated food source was a locally catered meal. Despite the presence of an aggressive Air Force public health program, foodborne illness had a major impact on manpower and medical resources during a critical phase of military operations. It is the recommendation of the authors that the Air Force not rely on local caterers during future deployments.

Aerospace Medicine↗

Influence of tamoxifen on plasma levels of insulin-like growth factor I and insulin-like growth factor binding protein I in breast cancer patients.

Plasma levels of insulin-like growth factor I (IGF-I) and insulin-like growth factor binding protein I (IGFBP-I) were measured in fasting blood samples obtained from 16 postmenopausal breast cancer patients before and during tamoxifen treatment for 1 to 6 months. Tamoxifen suppressed total plasma IGF-I by a mean of 28.5% (P less than 0.001) but elevated plasma IGFBP-I by a mean value of 78% (P less than 0.001). Changes in plasma levels of growth hormone, insulin, or insulin C-peptide were not observed. These findings suggest that tamoxifen exerts its influence on plasma IGF-I and IGFBP-I by mechanisms other than those known to regulate the plasma levels of these peptides, primarily growth hormone and insulin, respectively. A dual effect suppressing plasma IGF-I and elevating plasma IGFBP-I suggests that tamoxifen may have a significant influence on endocrine and possibly paracrine delivery of IGF-I to breast cancer cells in vivo.

Aged↗

Insulin-like growth factor II stimulates glucose transport in human skeletal muscle.

We investigated the effect of insulin-like growth factor II (IGF-II) and insulin-like growth factor binding protein-1 (IGFBP-1) on 3-O-methylglucose transport in incubated human skeletal muscle strips. Increasing physiological concentrations of IGF-II stimulated glucose transport in a dose-dependent manner. Glucose transport was maximally stimulated in the presence of 100 ng/ml (13.4 nM) of IGF-II, which corresponded to the effect obtained by 100 microU/ml (0.6 nM) of insulin. Exposure of muscle strips to IGFBP-1 (500 ng/ml) inhibited the maximal effect of IGF-II on glucose transport by 40%. Thus, it is conceivable that IGF-II and IGFBP-1 are physiological regulators of the glucose transport process in human skeletal muscle.

Adult↗

The assessment of carotid and vertebral arteries: a comparison of CFM duplex ultrasound with intravenous digital subtraction angiography.

The use of duplex ultrasound with colour flow mapping is compared with that of intravenous digital subtraction angiography (IVDSA) in the investigation of carotid and vertebral artery disease. Ninety-nine carotid and vertebral arteries were examined independently by IVDSA and ultrasound for location and degree of disease in 30 men (mean age 58) and 20 women (mean age 53). For purposes of comparison the carotid tree was divided into six segments. In 46% of cases no disease was detected by either modality. In 36% of cases where disease was found, ultrasound found mild disease in arteries reported as normal by IVDSA. Both modalities detected the six cases of total occlusion found in the study. IVDSA underestimated five cases of major disease found by ultrasound at the bifurcation or in the bulb. Overall agreement in grading vessel segments was good, with 74.5% in complete agreement and 90.3% grading stenoses to within +/- 25% of the other modality. There was good qualitative agreement in the findings for vertebral arteries. In four patients conventional arteriography was also available for comparison.

Adult↗

Potent effect of recombinant growth hormone on bone mineral density and body composition in adults with panhypopituitarism.

Six patients (21-50 years) with growth hormone deficiency and panhypopituitarism were given recombinant growth hormone, somatotropin, 0.04-0.1 U.kg.body wt-1.day-1, for 12 months. All patients reported improved well-being with increased working capacity. Bone mineral density, as measured by single photon absorptiometry at two sites on the forearm, showed increased values in 5/6 patients after 12 months when measured at the most distal site (predominantly trabecular bone) and in 4/6 at the more proximal site (predominantly cortical bone). Five patients continued therapy for an additional year and after 18 months a significant increase in bone mineral density was seen at both the distal and proximal sites. The mean annual increase in bone mineral density was 12.0 +/- 0.6 (SEM)% and 3.8 +/- 1.3% at the distal and proximal sites, respectively. In a growth hormone deficient control group without growth hormone therapy, the corresponding values were -2.4 +/- 0.6% and -1.9 +/- 0.4%, respectively. Lean body mass, estimated anthropometrically, increased significantly after 12 months and total body potassium, measured by whole body counting technique, increased in 4/6 patients. During growth hormone treatment, the IGF-1 values were above the mean values for age and 50% of the values were above the mean +2 SD. B-glucose, P-insulin, serum IGF-2, procollagen-III peptide and phosphate increased and urea, creatinine and IGF-binding protein-1 decreased during treatment. The beneficial effects of growth hormone substitution, especially on bone mineral density, indicate that growth hormone substitution should be considered in all patients with hypopituitarism and growth hormone deficiency, irrespective of age.

Adult↗

Plasma levels of insulin-like growth factor binding protein-1, and growth hormone binding protein activity from birth to the third month of life.

Serum levels of insulin-like growth factors (IGF-1 and IGF-2), insulin, insulin-like growth factor binding protein-1 (IGFBP-1), growth hormone (GH) and growth hormone-binding protein (GH-BP) activity were assessed in a group of healthy newborns and reevaluated at one and three months of life in six of them. A significant decrease in IGFBP-1 plasma levels was observed at one month (p < 0.002) and three months (p < 0.02) of life compared to cord blood values. IGF-1 plasma levels did not change during the first three months of life. In contrast, IGF-2 plasma levels increased significantly at three months of life compared to cord blood values (p < 0.002). GH plasma levels showed a significant decrease at three months of life (p < 0.03). GH-BP activity was low at birth and did not change significantly during the first three months of life. The low GH-BP activity may reflect the GH receptor status, indicating that GH receptors are poorly expressed in early infancy. The high IGFBP-1 plasma levels in newborns could be important in protecting them from hypoglycemia.

Aging↗