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Biomedical subjects

M S Christensen

Publications and source records attributed to M S Christensen.

At least 37 records · Page 2Linked to original sources
PubMed1989

Histomorphometric analysis of bone in idiopathic hypercalciuria before and after treatment with thiazide.

Twenty-seven normocalcemic patients aged 11-69 yrs with recurrent renal stone formation and idiopathic hypercalciuria were studied before and after treatment with hydrochlorthiazide (TD) 50 mg twice a day for 6 months. Hypercalciuria was defined as a 24 h renal calcium excretion of more than 7.5 mmol for males and 6.3 mmol for females. Quantitative histomorphometric analysis of iliac crest bone biopsies were performed before and after treatment. TD treatment increased the adjusted serum calcium level (p less than 0.01), whereas no significant effects on the serum levels of phosphorous, alkaline phosphatase or iPTH were found. The urinary calcium/creatinine ratio decreased (p less than 0.01) during TD treatment, whereas no change in the urinary phosphorous/creatinine ratio was found. The histomorphometric analysis revealed a reduction in the extent of eroded surfaces (p less than 0.05) and bone formation rate (p less than 0.05) as well as a decrease in the osteoid thickness (p less than 0.05) during TD treatment. No effect on the trabecular bone volume was found. A reduction in the activation frequency of new remodeling sites and thereby a reduced bone turnover during TD treatment can explain the observed histomorphometric changes. The decrease in osteoid thickness may be related to the increased serum calcium concentration leading to better conditions for mineralization.

Adult↗
PubMed1989

A histomorphometric determination of iliac bone remodeling in patients with recurrent renal stone formation and idiopathic hypercalciuria.

33 normocalcemic patients (22 males and 11 females) aged 20-68 years with recurrent renal stone formation and idiopathic hypercalciuria were compared to 33 approximately sex- and age-matched normal controls. Quantitative histomorphometric analysis of iliac crest biopsies were performed after intravital tetracycline double labeling in the patients and in 30 sex- and age-matched normal controls. No difference was found between patients and controls in albumin adjusted serum calcium levels. Serum phosphorus was significantly reduced (p less than 0.01) in the patient group whereas the urinary phosphorus/creatinine ratio was increased (p less than 0.01). The serum calcium phosphate product (S-CaxS-P) was significantly reduced in the patients (p less than 0.05). As expected, the urinary calcium/creatinine ratio was higher in the patient group than in the controls (p less than 0.001). Serum parathyroid hormone was normal. The histomorphometric analysis revealed signs of a moderate mineralization defect (reduced adjusted appositional rate (p less than 0.05), prolonged mineralization lag time (p less than 0.05) and prolonged formation (p less than 0.05)), and an increased extension of eroded surfaces (P less than 0.05) in the patients. The amount of trabecular bone and the balance between the thickness of bone resorbed and later formed per remodeling cycle and all other histomorphometric parameters were found normal in the patients. The combined histomorphometric and biochemical data are best explained by a primary renal phosphate leak leading to hypophosphataemia and a slight mineralization defect. The hypercalciuria may be explained by an enhanced renal production of 1.25-dihydroxyvitamin D secondary to the reduced serum levels of phosphorus. No signs of secondary or primary hyperparathyroidism were observed.

Adult↗
PubMed1986

Serum lipoprotein changes in climacteric women induced by sequential therapy with natural estrogens and medroxy-progesterone acetate or norgestrel.

Thirty perimenopausal women were randomized to sequential therapy with either estradiol-valerate and norgestrel (Cyclo-Progynon), or estradiol and medroxy-progesterone acetate (EM 627). Blood samples were drawn before treatment and in the third treatment cycle during estrogen and progestogen phases respectively. The clinical effects of the two treatments were without significant difference. Ovulation was not suppressed by the treatments, which induced similar increases in serum estradiol and estrone concentrations. The medium serum high density lipoprotein-(HDL)-cholesterol concentration expressed as a percentage of the pretreatment level decreased in the postmenopausal women treated with Cyclo-Progynon to 90% compared with 104% (p less than 0.01) in the EM 627 group. However, the concentrations expressed in mmol/l did not differ significantly, probably owing to non-significant differences in the pretreatment levels. Low density lipoprotein-(LDL)-cholesterol concentrations decreased by approximately 10% in the postmenopausal women during both treatments. Cyclic addition of medroxy-progesterone acetate to estrogen replacement therapy does not adversely affect the serum lipoprotein pattern, and may be preferable to norgestrel.

Adult↗
PubMed1986

The effect of glucagon, glucagon-(1-21)-peptide, and placebo on duodenal pressure activity in healthy subjects.

The effects of glucagon and the glucagon-(1-21)-peptide on the duodenal pressure activity in 12 healthy subjects were studied and compared with those of placebo. A 1-mg bolus injection of either glucagon or glucagon-(1-21)-peptide was given at the end of the first interdigestive migrating complex, followed by intravenous infusion of 2 mg of each drug during the subsequent 2 h. Both glucagon and glucagon-(1-21)-peptide caused significant change (p less than 0.05) in the duodenal pressure activity, as the length of the cycle was significantly increased and the migrating motor complexes were significantly reduced. The frequency of side effects and the degree of discomfort during the recordings were significantly higher (p less than 0.01) in the glucagon period than in both the glucagon-(1-21)-peptide and the placebo periods. No differences in side effects and discomfort between glucagon-(1-21)-peptide and placebo were detected. Glucagon caused a significant increase in both serum glucose and insulin levels (p less than 0.01).

Adult↗
PubMed1985

Triphasic oral contraception: metabolic effects in normal women and those with previous gestational diabetes.

The effect of a low-dose triphasic oral contraceptive (ethinyl estradiol and levonorgestrel) on glucose tolerance, plasma insulin and glucagon responses to glucose, fasting plasma cortisol, triglycerides, free fatty acids, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and very--low-density lipoprotein cholesterol was investigated in 16 women with previous gestational diabetes and in 19 normal women. Investigations were performed prior to the hormonal intake and after treatment for 2 and 6 months. Before treatment, the women with previous gestational diabetes had significantly elevated fasting glucose (p less than 0.05) and impaired glucose tolerance (p less than 0.05) when compared to those of the healthy control subjects. The glucose, insulin, and glucagon responses to oral glucose remained unchanged during the treatment period. Plasma cortisol increased in both groups (p less than 0.05) whereas plasma triglycerides increased in the control subjects only (p less than 0.05). Plasma free fatty acids, lipoproteins, and high-density lipoprotein cholesterol/total cholesterol ratio remained unchanged in both groups. The results suggest that a low-dose triphasic oral contraceptive (ethinyl estradiol and levonorgestrel) is suitable as contraception even in women with a previous deterioration of glucose tolerance during pregnancy.

Adult↗
PubMed1984

Low-risk lipoprotein pattern in post-menopausal women on sequential oestrogen/progestogen treatment.

Female hormones are known in influence serum lipoproteins. In post-menopausal women oestrogens decrease the concentration of low-density lipoprotein (LDL) and increase that of high-density lipoprotein (HDL), while progestogens may have the opposite effect. The risk of coronary heart disease (CHD) should consequently be decreased by oestrogens and increased by progestogens. We report here the changes observed in serum total cholesterol, triglycerides, and lipoproteins in post-menopausal women during sequential oestrogen/progestogen treatment. Oestriol and 17 beta-oestradiol were given alone for the first 12 days, in combination with norethisterone acetate (1 mg/day) for the next 10 days, and then in reduced amounts for the last 6 days of the 28-day cycle. Three different doses of the oestrogens were investigated (high, medium and low). A total of 177 normal post-menopausal women volunteered for random allocation to treatment or placebo groups. Blood samples were taken every 3 mth during the progestogen phase of the cycle. Serum total cholesterol was found to be 10-13% lower over a 3-yr period on the high oestrogen dose and 5 and 3% lower on the medium and low doses, respectively. No significant changes were seen in serum triglycerides. Determination of lipoprotein fractions showed that the reduction in total cholesterol was due to reduced LDL-cholesterol, the HDL-cholesterol levels remaining virtually unchanged.

Adult↗
PubMed1983

Plasma concentrations of megestrol acetate and medroxyprogesterone acetate after single oral administration to healthy subjects.

Plasma concentrations of megestrol acetate (MA) were measured by radioimmunoassay (RIA) after a single oral dose of 60 mg either in the form of one tablet, or four 15 mg tablets, to 10 women 21-40 years old using a cross-over design. No statistically significant difference between the two preparations was observed with respect to plasma concentrations, the area under the curve from 0 to 24 h or the maximum concentration (c(max)). For comparison, data are presented on the plasma level of medroxyprogesterone acetate (MPA) following a single oral dose of 100 mg given using a cross-over design in two different tablet forms to 10 healthy men, when no significant difference was observed for these parameters. The mean c(max) for MA after 2.6 h was 43.9 ng/ml (range 21.7-87.7 ng/ml), whereas that for MPA at 3.1 h was 13.1 ng/ml (range 4.4-29.5 ng/ml) despite the higher dose. After 24 h immunoreactive MA and MPA ranged from 9.6 to 29.0 ng/ml and from 0.2 to 4.0 ng/ml respectively. Moreover, it was found that petroleum ether extraction gives the most specific result by RIA, although considerable amounts of metabolites are still co-estimated. By comparison with selected ion monitoring using GC-MS, metabolite interference in RIA increases with time after administration of the steroids and is considerably greater for MPA than for MA. It is concluded that after oral administration the relative bioavailability of MA is significantly better than that of MPA.

Journal Article↗
PubMed1983

Decreased serum concentration of ionized calcium in insulin-dependent human diabetes mellitus.

Low serum ionized calcium concentrations were observed in twenty-five insulin dependent diabetic outpatients compared with twenty-three age-matched normal subjects: mean 1.16 mmol/l (SEM 0.01) versus 1.20 mmol/l (0.01), P less than 0.002. Despite this, there was no compensatory increase in serum concentrations of immunoreactive parathyroid hormone, nor was serum total calcium decreased in the diabetic patients. Serum magnesium was significantly decreased in the diabetics compared with normals: mean 0.75 mmol/l versus 0.83 mmol/l, P less than 0.001. No significant correlation could be demonstrated between serum magnesium and serum ionized calcium or parathyroid hormone in the diabetic patients. Since no significant correlations were observable between serum ionized calcium and indices of diabetes control, the etiology and pathogenesis of decreased serum calcium ion in insulin-dependent human diabetes mellitus remain unknown.

Adolescent↗
PubMed1983

Vitamin D and bone mineral content after intestinal bypass operation for obesity.

Twenty-three obese subjects who had undergone intestinal bypass operation (end-to-side jejunostomy) were studied with respect to vitamin D and other indices of calcium metabolism. Group 1 (11 patients) was examined before and one year after operation. Group 2 (12 patients, bypass operated two to seven years earlier was investigated twice with an interval of one year. The two groups were comparable. Bone mineral content and alkaline phosphatases were unchanged during the study in both groups. Bone phosphorus/hydroxyproline ratio was high postoperatively indicating a high degree of bone mineralisation. Serum calcium declined rapidly in group 1 to a constant level, which was maintained in group 2. The serum levels of iPTH and 1,25(OH)2D did not change within each group, but combining the two groups demonstrated an increase/decrease in iPTH/1,25(OH)2D over the years. The findings suggest that factors other than 1,25(OH)2D and iPTH are involved in calcium metabolism in such patients. The findings do not justify routine administration to such patients of high potency vitamin D derivatives, f.ex. 1 alpha-OH-D3.

25-Hydroxyvitamin D 2↗
PubMed1982

Dose-response evaluation of cyclic estrogen/gestagen in postmenopausal women: placebo-controlled trial of its gynecologic and metabolic actions.

In order to study dose-response relationships of estrogen in normal postmenopausal women, 100 volunteers were randomized to 12 months' treatment with placebo or one of three different doses (high, medium, or low) of natural estrogens (17 beta-estradiol and estriol), sequentially combined with norethisterone acetate for 10 of the 28 cycle days. A total of 87 women completed the trial with examinations every 3 months. Relief of climacteric symptoms was dose related, being 70%, 56%, and 33% in the high, medium, and low estrogen groups and unchanged in the placebo group. Regular vaginal bleeding occurred in 78% receiving high-dose in 64% receiving medium-dose, and in 40% receiving low-dose estrogen. Bone mass increased in the high and medium groups, was unchanged in the low group, and declined in the placebo group. Dose-related decreases in serum cholesterol of 10%, 5%, and 3% occurred in the three respective estrogen groups. Serum triglyceride levels, blood pressure, and body weight remained unchanged in all groups.

Adult↗
PubMed1982

Hyponatremia and hyperkalemia in relation to hyperglycemia in insulin-treated diabetic out-patients.

Interrelations between glucose and electrolyte homeostasis were evaluated in 193 insulin-treated diabetic out-patients. All had normal serum creatinine and were studied during their everyday metabolic control. Although the patients were selected to be without proteinuria and ketonuria, they exhibited wide ranges of blood glucose values (2.5-29.5 mmol/l) and urine glucose excretions (0-301 mmol/mmol creatinine). Patients with blood glucose values within 2.5-10 mmol/l (n = 80) had entirely normal levels of serum sodium (140.6 +/- 2.7 (SD) versus 141.0 +/- 2.6 mmol/l) and potassium (4.35 +/- 0.38 versus 4.40 +/- 0.38 mmol/l) as compared with normals (n = 371). In contrast, diabetics with higher blood glucose concentrations (n = 113) showed hyponatremia (137.7 +/- 2.6 mmol/l, p less than 0.001) and a moderate increase of serum potassium (4.60 +/- 0.39 mmol/l, p less than 0.001). On stratification into classes of blood glucose, serum sodium declined from 142 to 135 mmol/l (r = -0.61, p less than 0.001), whereas serum potassium rose from 4.33 to 4.87 mmol/l (r = 0.37, p less than 0.001). Despite these reciprocal changes the urinary excretion rates relative to creatinine of sodium potassium and water rose with rising degrees of glycosuria (r = 0.24, p less than 0.001; r = 0.28, p less than 0.001; and r = 0.63, p less than 0.001, respectively). The decline in serum sodium represents a well-known osmoregulatory response to hyperglycemia. However, the rising level of serum potassium in virtual absence of renal failure and ketonuria suggests an abnormality in potassium homeostasis. Diabetic dysregulation, or rather insulin deficiency may be its cause.

Cross-Sectional Studies↗
PubMed1982

Thiazide for the postponement of postmenopausal bone loss.

The effect of thiazide on bone mineral loss in normal postmenopausal women was examined during a 3 yr placebo-controlled clinical trial. Sixty-three healthy women in their early menopause were randomized to treatment with bendroflumethiazide 5 mg/day or placebo for 2 yr, while both groups received placebo for the third year of the trial. Calcium supplement 0.5 g/day was given throughout the 36 mo to all participants. Bone mineral content (BMC) determined by 125I-photon absorptiometry of the forearms decreased 2% per year in the placebo group (p less than 0.001). In the thiazide group no fall in BMC was seen during the first 6 mo. whereafter BMC declined with the same rats as in the placebo group. At the end of the 3 yr trial BMC averaged 94.1% in the placebo group and 95.2% in the thiazide group (p greater than 0.05). Despite a daily supplement of 0.5 g calcium, thiazide induced a persistent fall in the urinary calcium excretion of 25% (p less than 0.001), whereas the calcium supplement in the placebo group caused a significant increase in mean urine calcium of 10%-20% (p less than .001). At stop of thiazide medication a rebound effect caused a marked rise in urine calcium. One month after withdrawal of the calcium supplement the urinary calcium excretion had returned to the initial level in both groups. It is concluded that despite a sustained urine calcium lowering action the effect of thiazide upon postmenopausal bone loss is shortlived.

Alkaline Phosphatase↗
PubMed1982

Effect of lipids on the aggregation and permeability of human stratum corneum.

The role of stratum corneum (SC) constituents in SC barrier properties was assessed directly in vitro in a reaggregated system. Fragments of SC from the sole of the foot (hyperplastic tissue) and from the calf (normal tissue) were reduced, separately, to individual cells and these cells were depleted of lipids by solvent extraction. Lipids taken from the cells themselves or from SC from other areas of the body were then added to the cells. None of the fractions used allowed for reaggregation of plantar SC cells, or of trypsinized calf SC cells. In contrast, calf SC cells reaggregated equally well with all lipids and formed coherent SC sheets. At equal lipid:cell ratios, however, plantar lipid-calf cell SC sheets were about three time more permeable to water than calf lipid-calf cell SC sheets. The effectiveness of the barrier function of the SC sheets was directly proportional to the amount of added lipid. We conclude that in normal SC the extractable lipids are intimately involved in cellular adhesion/dyshesion and in barrier formation.

Animals↗
PubMed1982

Renal hypomagnesaemia in human diabetes mellitus: its relation to glucose homeostasis.

Interrelations between magnesium and glucose metabolism were studied in 215 insulin-treated diabetic out-patients aged 7-70 years. All had normal serum creatinine concentrations (below 115 mumol/l) and none had other diseases or received drugs known to interfere with mineral metabolism. A definite hypomagnesaemia (less than normal mean - 2 SD) and hypermagnesiuria (greater than normal mean + 2 SD) occurred in 38.6% and 55% of the patients. In the presence of hypermagnesiuria the serum magnesium concentration was inversely correlated to the urinary magnesium excretion rate (R = -0.23, P less than 0.02). Serum magnesium correlated inversely with both fasting blood glucose (R = -0.32, P less than 0.001) and the urinary glucose excretion rate (R = -0.22, P less than 0.005). The urinary magnesium excretion rate correlated directly with the same variables (R = 0.27, P less than 0.001 and R = 0.58, P less than 0.001, respectively). These data indicate that the net tubular reabsorption of magnesium is decreased in diabetic patients in presence of hyperglycaemia, leading to hypermagnesiuria and hypomagnesaemia.

Adolescent↗
PubMed1982

Pathophysiological mechanisms of estrogen effect on bone metabolism. Dose-response relationships in early postmenopausal women.

Dose-response relationships of estrogen (E) on indices of calcium balance and bone activity were studied in normal early postmenopausal women. Calcium balance was estimated by changes in forearm bone mineral content, measured by photon absorptiometry. Bone activity was estimated by serum alkaline phosphatases (S-aPh), indicating bone formation, and by fasting urinary excretion of hydroxyproline (U-HyPro) and calcium (U-Ca), indicating bone resorption. A total of 92 female volunteers were randomized to 12 months' treatment with placebo or one of three different doses (high, medium, or low) of natural estrogens (17 beta-estradiol and estriol, 4/2, 2/1, and 1/0.5 mg, respectively), sequentially combined with the same dose (1 mg) of norethisterone acetate for 10 of the 28 cycle days. The trial was completed by 79 women. Bone mineral content declined by 2% (P less than 0.001) in the placebo group, remained constant in the low hormone group and increased by 0.8% (P less than 0.05) and 1.5% (P less than 0.01), respectively, in the medium and high hormone groups. S-aPh decreased gradually and equally by 20-25% in the three hormone groups and U-HyPro and U-Ca decreased by 30-40% during 1-yr hormone treatment, irrespective of dose. The decrease in these three indices occurred practically without exceptions. Compared to the values found in 48 normal premenopausal women the untreated postmenopausal women had increased values of S-aPh (P less than 0.001), U-HyPro (P less than 0.01), and U-Ca (P less than 0.001), and no pretreatment values were below the normal premenopausal range. After treatment the mean values of S-aPh and U-HyPro were slightly lower than the premenopausal mean values (P less than 0.01). These data strongly support the major importance of E deficiency for early postmenopausal bone loss, which is prevented by even a small substitution dose of E.

Adult↗