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Biomedical subjects

H K Ibbertson

Publications and source records attributed to H K Ibbertson.

At least 37 records · Page 2Linked to original sources

The effects of hydrocortisone, parathyroid hormone and the bisphosphonate, APD, on bone resorption in neonatal mouse calvaria.

The effects of hydrocortisone and parathyroid hormone (PTH) upon bone resorption rates in neonatal mouse calvaria have been studied. Bone resorption (measured as 45Ca release) was significantly increased by hydrocortisone (10(-7) M and 10(-6) M) and there was a dose-dependent rise with PTH (0.3-0.9 micrograms/liter). When both PTH 0.3 micrograms/liter and hydrocortisone 10(-8) M were present in the incubating medium, bone resorption did not differ from control, but increasing the hydrocortisone concentration to 10(-7) M augmented 45Ca release by 25% (P less than 0.02) and doubling of the PTH level was associated with a 10% increase (nonsignificant). When both PTH and hydrocortisone were present in the higher concentrations (0.6 micrograms/liter and 10(-7) M, respectively) 45Ca release increased by 39% (P less than 0.005) above that resulting from the lower levels of both hormones (0.3 micrograms/l and 10(-8) M, respectively). (3-Amino-1-hydroxypropylidene)-1,1-bisphosphonate (APD) in concentrations of 3 X 10(-5) M and 10(-4) M, produced inhibition of basal and hydrocortisone/PTH-stimulated bone resorption without evidence of toxicity. These results indicate that hydrocortisone stimulates bone resorption in neonatal mouse calvaria in vitro, in contrast to the results found in fetal rat bone culture systems. PTH has a similar effect, which is additive to that of hydrocortisone and the combined stimulation can be overcome by APD. The possible relevance of these results to the development and prevention of glucocorticoid-induced osteoporosis is discussed.

Animals↗

The assessment of intestinal calcium absorption using stable strontium.

The availability of currently used methods of measuring intestinal calcium absorption is limited by their expense and complexity. Since this measurement may be important in selecting appropriate therapies for patients with osteoporosis, a simpler procedure is required. This paper describes a test which measures the intestinal absorption of stable strontium. A comparison of this test with the single-isotope radio-calcium absorption test in the same group of patients showed a close correlation between the fractional absorption rates of the two elements (r = 0.93, P less than 0.001). Subjects were correctly categorized as having normal or low absorption in 12 out of 13 cases (92%) and the value in the misclassified subject was at the borderline between normal and low calcium absorption. The convenience, low cost, and freedom from radioactivity of stable strontium make it suitable for routine clinical use and, if necessary, repeated testing. If these early results are confirmed, this test will make the assessment of calcium absorption much more widely available.

Aged↗

Calcium supplements in the prevention of steroid-induced osteoporosis.

The long-term use of glucocorticoid drugs frequently results in the development of osteoporosis. To assess the value of calcium supplementation in preventing this loss of bone, the metabolic effects of administering 1 g of elemental calcium/day have been studied in 13 steroid-treated patients. After 2 mo, the fasting urine hydroxyproline-creatinine ratio decreased from 27.1 +/- 2.5 (SEM) to 21.8 +/- 2.4 (p less than 0.001) and there was an increase in fasting urine-calcium excretion (p less than 0.05). Serum alkaline phosphatase and osteocalcin showed no change. We concluded that calcium supplementation suppresses bone resorption without detectable suppression of indices of bone formation and is, therefore, likely to result in increased bone mass. The safety and low cost of calcium make it a very suitable prophylactic agent in glucocorticoid-treated patients.

Adolescent↗

The acute biochemical effects of four proprietary calcium preparations.

Changes in serum and urine biochemical indices have been studied in ten normal subjects in the four hours following the ingestion of four proprietary calcium supplements. Each was taken in a dose containing 1 gram of elemental calcium. The four preparations were ranked according to the amount of calcium absorbed in the order Spar-Cal and Calcium Sandoz greater than Os-Cal greater than Ossopan. There were no significant differences between the four preparations in the changes in parathyroid hormone (PTH) and urine hydroxyproline levels. For this reason, the four results from each subject were averaged. Following the calcium load there was a reduction in mean PTH from 0.16 +/- 0.01 to 0.10 +/- 0.02 micrograms/l (p less than 0.001) and a decline in urine hydroxyproline/creatinine ratio from 20 +/- 1 to 17 +/- 1 (p less than 0.02), suggesting that bone resorption responds immediately to dietary calcium intake. There was a rise in urine sodium excretion which correlated with the indices of calcium absorption (r = 0.63, p less than 0.01) but not with the sodium content of the calcium preparations. This effect could be important, particularly in elderly patients on borderline sodium intakes.

Administration, Oral↗

Low serum osteocalcin levels in glucocorticoid-treated asthmatics.

Serum osteocalcin (OC) levels were measured in 19 asthmatic patients receiving long term glucocorticoid therapy and in age- and sex-matched asthmatic patients not receiving this treatment. In the glucocorticoid-treated patients, the mean OC level was approximately 50% less than that in the control group (P less than 0.001), and there was a direct correlation between serum OC and 1,25-dihydroxyvitamin D [1,25-(OH)2D; r = 0.71; P less than 0.001]. Multiple regression analysis in a total of 39 glucocorticoid-treated patients indicated that OC correlated directly to 1,25-(OH)2D and inversely to glucocorticoid dose. There was no correlation between OC and 1,25-(OH)2D in the control group and no significant difference in mean serum 1,25-(OH)2D between the steroid-treated asthmatic patients and the asthmatic control patients. The effect of a 4-day course of oral 1,25-(OH)2D on serum OC was studied in six patients with glucocorticoid excess and six normal subjects. There was a similar percent increase in OC levels in both groups, though the basal concentrations and absolute increases were substantially less in the steroid-treated group. It is likely that the depression of serum OC in glucocorticoid-treated patients results from the reduction in the rate of bone formation induced by these hormones.

Administration, Oral↗

The screening of patients with suspected thyrotoxicosis using a sensitive TSH radioimmunoassay.

A radioimmunoassay was optimized to measure serum TSH with maximum sensitivity (sTSH). With this assay sTSH was less than 0.5 mIU/l in 100% of 64 patients with proven thyrotoxicosis and greater than 0.5 mIU/l in 92% of 76 normal subjects. sTSH correctly predicted the TSH response to TRH (delta TSH) in 93% of 125 patients with suspected thyrotoxicosis. In this group thyrotoxicosis was excluded by an sTSH greater than 0.5 mIU/l in 52% of patients thus avoiding the need for further testing.

Humans↗

Objective assessment of treatment response in hirsutism.

A simple photographic technique was used to assess the objective response of hirsute women to treatment with cyproterone acetate (CA). The skin in front of the left ear was shaved and photographs taken immediately and after 1 week, and hair growth per week estimated by averaging the length of 20 hairs in the magnified photographs. The precision, repeatability and patient acceptance of the method were found to be satisfactory. Basal hair growth rates were 2.28 +/- 0.4 mm/week (mean +/- SD, n = 34) and showed a significant correlation with hirsutism scores derived from a standard physician-rated scale. During therapy with CA the mean (+/- SD) improvement in hair growth rate was 19 +/- 13%, whereas physician-rated hirsutism scores improved by 33 +/- 20%. The reduction in hair growth rate showed no significant correlation with improvement assessed using subjective rating by either physician or patient. The greater improvement in physician-rated scores compared with hair growth rate assessment suggests that hair shaft width, colour and other factors may be as important as hair length when assessing treatment response.

Adolescent↗

Cyproterone acetate as initial treatment and maintenance therapy for hirsutism.

Thirty-four patients with hirsutism were treated for 9 months with 100 mg cyproterone acetate (CA) given on days 5-15 of the menstrual cycle together with a combination oral contraceptive containing 2 mg CA and 50 micrograms ethinyloestradiol (Diane) given on days 5-25 of the cycle. After 9 months treatment patients were randomised to a 12 month double-blind cross-over trial comparing Diane plus 25 mg CA with Diane plus placebo, to test the efficacy of low-dose CA as maintenance therapy. Thirty-one patients (92%) experienced moderate or good subjective improvement in hirsutism on high-dose CA, associated with a 40% mean overall improvement in objective hirsutism grade and 13% overall reduction in hair growth rate measured by a photographic technique. Minor or moderate side effects were experienced by 64% of patients and severe side effects by 11% at this dosage. There was a mean subjective relapse rate of 33% when patients were changed to low dose CA, and relapse rates were not significantly different between the two regimens with 28% relapsing on 25 mg CA + Diane and 48% on placebo and Diane (P less than 0.05). Despite significant subjective relapse with low-dose treatment there was no significant deterioration in objective hirsutism grade or hair growth rate determined photographically. Levels of plasma testosterone, sex hormone binding globulin, free testosterone (derived) and androstenedione fell significantly on high dose CA and this reduction was maintained during low dose therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Iodine intake in an urban environment: a study of urine iodide excretion in Auckland.

Dietary iodine intake was estimated by measurement of iodide in random overnight 12 hr and 24 hr urine samples. Urinary iodide excretion was measured in 231 healthy females comprising 127 female secondary students (ages 16-19), 27 female tertiary students (17-23 yr), 42 female laundry workers (18-52 yr) and 26 pregnant women in the third trimester (18-40 yr). Urine iodide excretion was also examined in a group of 28 patients attending a thyroid clinic, with thyroid disease of diverse aetiology and in 34 patients taking the antiarrhythmic drug amiodarone for control of cardiac arrhythmias. The mean daily urine iodide excretion was 2.4 mumol/day (0.9-5.8 mumol/day) and iodide to creatinine ratio 0.21 mumol/mmol (0.09-0.29). Iodine deficiency (less than 0.4 mumol/day) was not observed in any subject. Excessive iodine (greater than 8 mumol/day) was found only in patients known to be taking iodine-containing drugs and in one normal individual. The urine iodide was normal in 154 female students, 14 of whom had a trivial thyroid enlargement. The study suggests that dietary sources other than iodised salt contribute significantly to dietary iodine intake and that residual goitre in the community is not secondary to deficiency or excess of dietary iodine.

Adolescent↗

Effective oral treatment of severe Paget's disease of bone with APD (3-amino-1-hydroxypropylidene-1,1-bisphosphonate); a comparison with combined calcitonin + EHDP (1-hydroxyethylidene-1,1-bisphosphonate).

Ten patients with severe Paget's disease of bone and serum alkaline phosphatase (sAP) greater than 900 IU/l were treated for six months with the oral diphosphonate APD, (3-amino-1-hydroxypropylidene-1, 1-bisphosphonate). By the end of the treatment period there was a reduction in the log mean urine hydroxyproline (uHP) and the log mean sAP of 92% and 87% respectively. In four patients both sAP and uHP fell to within the normal range and remained normal for at least six months after therapy was stopped. Bone scintigraphy showed a fall in 99mTc-MDP uptake in sites of active Paget's disease in all patients and histomorphometry showed no increase in osteoid. Repair of radiological osteolytic lesions was observed in 6/6 patients and progression of tibial osteolytic wedges was arrested in 5/5 patients and reversed in four. This improvement persisted six months after completion of therapy but further wedge progression occurred in one patient whose urine HP remained elevated. There were no serious effects though five patients complained of nausea. The clinical and biochemical responses to APD were equivalent to those observed in the same patients during a previous six month course of combined therapy with human calcitonin (CT) + EHDP except that there was additional biochemical and radiological evidence of bone healing. This study confirms PAD as an effective treatment of severe Paget's disease of bone.

Aged↗

Clinical and biochemical evaluation of patients with hirsutism.

Patients with moderate to severe hirsutism presenting over an 18-month period to an endocrine clinic were assessed by clinical evaluation and hormone measurements. Hair growth rate was estimated by a photographic technique and the severity of hirsutism graded using an objective scale. Of 43 patients, 9 had polycystic ovaries and the remainder were considered to have idiopathic hirsutism. The most severely affected group had significantly increased hair growth rates compared with less clinically affected subjects, and 47% of this group showed objective features of virilization. However, apart from a significantly higher 24-hr urine 17-ketosteroid excretion all other hormonal patterns were not significantly different between severely and mildly affected patients. Serum levels of testosterone (T), sex hormone-binding globulin (SHBG), free T (calculated from T and SHBG values), and androstenedione (A) were abnormal in 44%, 51%, 60% and 60% of patients respectively, whereas plasma levels of the specific adrenal androgen DHAS were increased in 40% of patients. There was an overlap between patients with elevated hormone levels, although isolated elevation of T, A or DHAS were seen in 9%, 19% and 3% of patients respectively. In 19% of patients all serum androgen measurements were normal. Gonadotrophin levels were significantly lower in the more severely affected group. Thus androgen levels in patients with idiopathic hirsutism or polycystic ovaries, show considerable overlap with measurements in normal subjects, and elevated plasma androgens may be of adrenal (DHAS) or combined adrenal/ovarian (T, A) origin.

17-Ketosteroids↗

Low thyroxine levels in some hyperprolactinemic patients due to dopaminergic suppression of thyrotropin.

The serum free T4 index (FT4I) was at or below the lower limit of normal in 8 of 55 unselected patients with hyperprolactinemia. Serum levels of T3 were normal and none of the patients had clinical evidence of hypothyroidism. In patients with low FT4I the serum TSH was within the normal range and TSH was released normally after administration of TRH, indicating normal pituitary TSH reserve. Serum TSH also increased after administration of the dopamine antagonist domperidone. The TSH response to domperidone was significantly greater in the hyperprolactinemic group with low FT4I compared with either normal subjects or hyperprolactinemic patients with normal FT4I, suggesting that depression of FT4I was due to increased dopaminergic activity. Administration of the dopamine antagonist metoclopramide for 4 days led to a supranormal rise in FT4I in 3 of 5 patients with low FT4I. Thus, a minority of hyperprolactinemic patients have a low FT4I which appears due to excessive hypothalamic production of dopamine.

Adult↗

Iodide enhances IgG synthesis by human peripheral blood lymphocytes in vitro.

Several studies have suggested that iodide may increase thyroiditis and autoantibody synthesis. We have investigated the effect of iodide in vitro at physiologically relevant concentrations on immunoglobulin synthesis by normal human peripheral blood lymphocytes stimulated with pokeweed mitogen. Both the number of cells which synthesised IgG and the amount of IgG released into the culture supernatant increased significantly after culture in a medium with added iodide compared to a medium with added chloride. No effect of increasing concentrations of the added iodide from 10(-3) mM to 10 mM was observed. These findings suggest that iodides may have a role in enhancing antibody synthesis which may be important when programmes of iodide supplementation are introduced into areas which are deficient.

Adult↗

Effect of cyproterone acetate on glucocorticoid secretion in patients treated for hirsutism.

The effect of cyproterone acetate (CA) on adrenal glucocorticoid secretion was studied in 35 women with hirsutism. Patients were treated for 9 months with 100 mg CA orally 10 days each month, administered in reverse sequence with 21 days of a combination oral contraceptive containing 50 micrograms ethinyloestradiol and 2 mg CA. During treatment one patient had a mildly impaired plasma cortisol response to insulin-induced hypoglycaemia and 2 patients showed slight reduction of the plasma cortisol response to ACTH. Responses to metyrapone were normal in all patients tested. Overall, the mean response to these tests was significantly greater during CA treatment compared with pre-treatment measurements, probably due to effects of oestrogen on cortisol-binding globulin. In all patients urinary cortisol excretion remained normal and no patient demonstrated any features of steroid insufficiency. Thus it appears that CA has no untoward effect upon glucocorticoid secretion when given in high dosage for prolonged periods to hirsute women.

17-Hydroxycorticosteroids↗

Carbimazole and autoantibody synthesis in Hashimoto's thyroiditis.

Serum thyroxine, thyrotrophin, and thyroid microsomal antibody levels were measured in 20 patients with Hashimoto's thyroiditis and hypothyroidism before, during, and after treatment with carbimazole or placebo. Thyroid microsomal antibody levels fell during treatment in the 10 patients who received carbimazole, while serum thyroxine and thyrotrophin levels did not change. There were no changes in the placebo group. The study proves support for the concept that carbimazole may act directly on autoantibody synthesising lymphocytes localised in the thyroid. Such an effect might be valuable in influencing the autoimmune process in autoimmune thyroid disease.

Autoantibodies↗

Coexisting Paget's disease of bone and hyperparathyroidism.

A patient with Paget's disease of bone and primary hyperparathyroidism is described. It has been suggested that a metabolite from pagetic tissue might stimulate parathyroid cell function. To test this, serum parathyroid hormone (iPTH) levels were measured by radio immunometric assay in 106 patients with Paget's disease of bone and 139 control subjects. There was no significant difference between the mean levels of the two groups. Of five sera with elevated PTH levels QUOSO extraction revealed an interfering substance in 3/5 from control patients tested and extractable iPTH in 2/2 from Paget's patients. One of the latter had renal failure. The results suggest that increased parathyroid function is unlikely to be a primary event in the genesis of Paget's disease of bone.

Aged↗

Subclinical hypothyroidism.

Clinical and biochemical indices of thyroid function were compared in 18 euthyroid control subjects and 54 patients at risk of developing hypothyroidism, and the assessment repeated after a four-week trial of oral triiodothyronine (T3) 40 microgram daily. Patients with minor elevation of the pre-treatment serum TSH concentration (5-15 microU/ml) showed significant reduction in the free thyroxine index (FTI), prolongation of the basal ankle reflex half-relasation time (ART), and shortening of the ART after oral T3 treatment, when compared either to control subjects or to patients with a normal TSH level. It is concluded that patients with minimal TSH elevation have minor but parallel abnormalities of both thyroid hormone concentration and action.

Humans↗