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Biomedical subjects

D Aarskog

Publications and source records attributed to D Aarskog.

At least 19 recordsLinked to original sources
PubMed1992

[Torsades de pointes ventricular tachycardia induced by disopyramide at therapeutic serum concentration].

We describe a patient who developed torsades de pointes ventricular tachycardia after several years of treatment with disopyramide. The case demonstrates that measuring disopyramide serum concentration provides limited information about correct dosages. Life-threatening arrhythmias may arise even at recommended doses and therapeutic serum concentration. Clinical trials have shown that class Ic antiarrhythmic drugs, and perhaps all class I antiarrhythmics, may increase the risk of serious arrhythmias and sudden death in certain groups of patients. Aspects of the pharmacology of disopyramide are discussed, with particular emphasis on the variable plasma protein binding and the narrow therapeutic specter. This complexity seems to be the most important reason for the limited reliability of serum concentration measurements for predicting the best dosage for the individual patient.

Aged↗
PubMed1992

Reorganization of the cytoskeleton and morphological changes induced by 1,25-dihydroxyvitamin D3 in C3H/10T1/2 mouse embryo fibroblasts: relation to inhibition of proliferation.

The effects of 1,25-dihydroxyvitamin D3 (1,25(OH)2 D3) on cell morphology, the cytoskeleton, and fibronectin were studied in three lines of C3H/10T1/2 mouse embryo fibroblasts in which the antiproliferative effect of the hormone had previously been investigated. We showed that 1,25(OH)2D3 induced morphological changes in the nontransformed C3H/10T1/2 Cl 8 cells, which flattened and spread out markedly. Visualization of actin and tubulin by immunocytochemistry disclosed a reorganization of the microfilament and microtubular systems. 1,25(OH)2D3 also induced an increase in cell-surface-associated fibronectin. These changes were only slight in the transformed cell line C3H/10T1/2 Cl 16 and absent in the transformed C3H/10T1/2 TPA 482 cell line. These effects were correlated with the growth inhibition induced by the hormone, and this suggests a possible relationship between the 1,25(OH)2D3-induced alterations of cell shape and of the cytoskeleton and the effects of the hormone on cell proliferation.

Actin Cytoskeleton↗
PubMed1992

Syndromes and genital dysmorphology.

External and internal genitalia can be malformed by genetic and environmental factors without involvement of sex chromosomes or fetal gonads. Thus, genital dysmorphology may be part of many syndromes of various etiology, such as monogenetic disorders, autosomal chromosomal abnormalities and non-random malformation syndromes of unknown etiology. Genital dysmorphology may also occur as a result of teratogenic effects following maternal ingestion of synthetic progestins. The genital manifestations in all these syndromes occur more commonly in males than in females. Penetrance and expression of these abnormalities tend to show great variability.

Abnormalities, Drug-Induced↗
PubMed1992

Regulation of cell growth, c-myc mRNA, and 1,25-(OH)2 vitamin D3 receptor in C3H/10T1/2 mouse embryo fibroblasts by calcipotriol and 1,25-(OH)2 vitamin D3.

Calcipotriol is a synthetic 1,25-(OH)2D3 analogue with high affinity for the 1,25-(OH)2D3 receptor, but with a lower affinity than 1,25-(OH)2D3 for vitamin D binding protein in serum. The inhibitory action of calcipotriol and 1,25-(OH)2D3 on proliferation of C3H/10T1/2 mouse embryo fibroblasts was examined in the non-transformed cell line Cl 8 and in the two transformed, tumorigenic cell lines Cl 16 and TPA 482. Upon exposure to 10 nmol/l calcipotriol or 1,25-(OH)2D3, the proliferation of Cl 8 cell line was almost completely suppressed, whereas both hormones had no effect on the cell lines Cl 16 and TPA 482. Calcipotriol was at least as effective as 1,25-(OH)2D3 in inducing up-regulation of the 1,25-(OH)2D3 receptor. Displacement studies showed no difference between calcipotriol and 1,25-(OH)2D3 in the affinity for the receptor present in Cl 8 or Cl 16 cell extracts. Furthermore, the inhibition of cell growth in Cl 8 cells by calcipotriol was not accompanied by any consistent change in the steady-state expression of c-myc mRNA. In conclusion, calcipotriol had potent growth inhibitory effect on the non-transformed cell line similar to 1,25-(OH)2D3. In the transformed cell lines, calcipotriol did not inhibit proliferation despite potent up-regulation of the 1,25-(OH)2D3 receptor.

Animals↗
PubMed1992

Serum vitamin D metabolites and calcitriol receptor concentration in parathyroid tissue in primary hyperparathyroidism.

Vitamin D metabolites in serum and calcitriol receptor concentration in parathyroid tissue were examined in 52 patients operated on for primary hyperparathyroidism. The calcitriol receptor levels were not different in parathyroid adenomas (mean 224 fmol/mg of protein, range 29-509, N = 43), normal parathyroid tissue (mean 245, range 31-690, N = 20), and primary parathyroid hyperplasia (mean 172, range 46-477, N = 9). Preoperative serum levels of calcitriol concentration correlated inversely to the calcitriol receptor in normal parathyroid tissue in patients with adenoma (r = -0.57, N = 17, p = 0.017), but no such correlation was found in the corresponding adenomas (r = 0.14, p = 0.59). In 31 patients in whom both pre- and postoperative vitamin D metabolite analyses were carried out, 23 had lower calcitriol postoperative concentrations compared to preoperative values (p = 0.012, sign test). No change was found in the other vitamin D metabolites postoperatively. By multiple regression analysis calcitriol concentration in serum was inversely correlated to the serum concentration of urea and phosphate (p = 0.003). We conclude that calcitriol may influence calcitriol receptor expression in normal parathyroid tissue, but not in adenomatous parathyroid gland. Furthermore, serum calcitriol was correlated to the renal function, and phosphate level, and in most patients the calcitriol concentration was lower after the operation.

Adenoma↗
PubMed1990

Effect of 1,25-(OH)2-vitamin D3 on growth, homologous receptor and c-myc regulation in C3H/10T1/2 cells.

1,25-Dihydroxyvitamin D3 (1,25-(OH)2D3) receptor concentration, cell proliferation, and the steady-state level of c-myc mRNA were examined in the C3H/10T1/2 mouse embryo fibroblasts, before and after exposing the cells to 1,25-(OH)2D3. The non-transformed, logarithmically growing C3H/10T1/2 Cl 8 cells contained a high concentration of 1,25-(OH)2D3 receptor (164 fmol/mg of protein). An up-regulation of the 1,25-(OH)2D3 receptor and a potent inhibition of cell growth were observed by exposing the cells to 10 nM 1,25-(OH)2D3. The concentration of 1,25-(OH)2D3 receptor in the two chemically transformed, tumorigenic cell lines. C3H/10T1/2 Cl 16 and C3H/10T1/2 TPA 482, was 218 and 63 fmol/mg of protein, respectively. In the two transformed cell lines, 10 nM 1,25-(OH)2D3 had only negligible effect on cell growth. In the Cl 16 cells, an up-regulation of the 1,25-(OH)2D3 receptor was demonstrated, but only a weak up-regulation was found in the TPA 482 cells by the 1,25-(OH)2D3 treatment. No major changes were found in c-myc mRNA levels by the 1,25-(OH)2D3 treatment. Despite inhibition of cell growth, the steady-state level of c-myc mRNA was slightly induced (35%, mean) in the Cl 8 cells compared to control cells. In the transformed cells, no consistent change of the c-myc level was found. In contrast to earlier reports, we did not find any correlation between the 1,25-(OH)2D3 receptor and c-myc level, nor did we find any decrease of c-myc mRNA by 1,25-(OH)2D3 treatment in the C3H/10T1/2 fibroblasts.

Animals↗
PubMed1979

A familial syndrome of diaphyseal cortical thickening of the long bones, bowed legs, tendency to fracture and icthyosis.

The clinical and radiological features of a dominant bone disorder found in six members of the same family are described. The bone disorder was mainly characterized by endosteal cortical thickening of long tubular bones and bowing of the weight-bearing ones. The clinical symptoms were waddling gait, muscle weakness and leg pains, and there was a tendency to fractures. All affected individuals had icthyosis of slight or moderate degree.

Adult↗
PubMed1979

Oral aspects of osteopetrosis.

The characteristic feature of osteopetrosis is a lack of osteoclastic activity, leading to a series of somatic problems for afflicted persons. The life span of osteopetrotic patients has increased in recent years, thereby making oral aspects of the disease more evident. Four children with malignant osteopetrosis, born between 1967 and 1975, were examined. In all patients the anterior teeth were of normal shape, and erupted on schedule. Primary molars and all permanent teeth were greatly distorted, and remained totally or partly embedded in basal bone. Vertical growth of alveolar ridge was very limited. Where a fenestration of overlaying mucosa had occurred, a localized progressive osteitis developed, leading to soft tissue inflammation and, in two cases, extraoral mandibular fistulas. Peridontal attachment was very poor, spontaneous exfoliation had occurred in all patients. In two children tooth germs and necrotic bone were surgically removed. No beneficial effect of the treatment was observed. Large doses of antibiotics were needed to control recurring infections. No means of curing progressive osseous destruction of mandibular bone has been found. The general prognosis is poor.

Child↗
PubMed1979

Dental findings in patients with Aarskog syndrome.

Dental manifestations of the Aarskog syndrome were studied in 10 individuals. There was retarded development and eruption of the permanent teeth in six boys. Dental age was less retarded than height age and bone age. The prevalence of hypodontia and the prevalence and degree of orthodontic anomalies were higher than in the general population. Caries prevalence was high.

Abnormalities, Multiple↗
PubMed1979

Acute response of parathyroid hormone in congenital osteopetrosis.

Indices of calcium and phosphorus metabolism were studied in 3 children with osteopetrosis before and after infusion of bovine parathyroid hormone extract. Basal plasma concentrations of calcium, alkaline phosphatase and 25-hydroxy vitamin D tended to be low. Plasma immunoreactive PTH levels were at the upper normal range in two patients. A marked increase in urinary cyclic AMP in all patients was solely due to an increase in the nephrogenous cAMP. After vitamin D treatment urinary cAMP was essentially unchanged with the same preponderance of nephrogenous cAMP. Following PTH infusion plasma cAMP showed a brisk rise. There was also a prompt rise in urinary cAMP and a distinct decrease in the calcium to sodium clearance ratio indicating increased calcium reabsorption. Phosphaturic effect was only observed when PTH was given in the highest dose level. The findings are consistent with a state of low grade hyperparathyroidism which could not be related to the plasma levels of 25-hydroxy vitamin D or calcium.

Child↗
PubMed1978

Natural and immune antibodies to rabbit erythrocyte antigens.

Natural agglutinins to rabbit erythrocytes were found in all human sera studied. In the newborn, the antibodies were of IgG class; in the 6-month-old infants they were mainly of IgM class. Older children and adults had both IgG and IgM antibodies. Agglutinins to rabbit erythrocytes were also found in serum from fourteen of fifteen other species studied. The trichloroacetic acid extract from rabbit erythrocyte stromata (TCA-preparation) contains at least three different antigenic determinants: one which we hitherto to have found only on rabbit erythrocytes, one which is closely related to human blood group B antigen, and one which is closely related to the I antigen. The TCA-preparation did not elicit delayed hypersensitivity skin reactions in humans in spite of high titred agglutinins in serum, but did so in immunized guinea-pigs.

Adolescent↗
PubMed1978

Lymphocyte multiplication in vitro induced by mitogens and antigens.

A simple technique requiring only 0.2 ml whole blood for measuring the response of lymphocytes in cultures to each of various mitogens and antigens has been elaborated. The response is quantified by comparing the number of lymphocytes with and without a stimulating agent. The increment of cell numbers is given by a cell multiplication index. In healthy subjects PHA induced almost a doubling of the cell numbers in 3 days, i.e. an index of 1.90 +/- 0.38. After 7 days the indexes for PHA, PWM and Con A were 7.25 +/- 4.12, 2.72 +/- 0.65 and 1.81 +/- 0.31, respectively. PPD and Candida-extract induced cell multiplication in skin positive individuals, with indexes ranging from 1.12 to 3.05. In contrast, patients with various severe immune deficiencies showed decreased responses to at least one mitogen, depending on the type of the deficiency. Likewise, skin test negative individuals had no or faint in vitro response to the antigens. The method, which correlated well with the response by a conventional method for incorporation of tritiated thymidine, has a high degree of precision and sensitivity, and should be applicable for routine use.

Adult↗
PubMed1978

Alpha-1-antitrypsin (Pi)-types in recurrent miscarriages.

Chromosome analysis was carried out in a consecutive series of 57 couples with a history of recurrent miscarriage. All 114 subjects from these couples had normal karyotypes by conventional analysis. Pi typing was performed in 30 couples. The constellation of Pi heterozygosity in both partners occurred in two of the couples. The expected frequencies of the observed MS-MS and MS-MZ constellations occurring by chance would be 2.1 per 1,000 and 2.2 per 1,000 couples, respectively.

Abortion, Spontaneous↗
PubMed1977

The effect of the stimulant drugs, dextroamphetamine and methylphenidate, on secretion of growth hormone in hyperactive children.

The stimulant effect of L-dopa (125 to 500 mg) was compared to dextroamphetamine and methylphenidate, 15, and 20 mg, respectively, on growth hormone secretion in 20 hyperactive children. All three stimulants were responsible for peak GH concentration in serum at 60 minutes after drug ingestion; there was no significant difference between the mean GH level at any time of sampling. Seven of the children were retested with L-dopa and dextroamphetamine after six to eight months of treatment with methylphenidate. After treatment, there was a tendency to higher zero time levels of GH, and to delayed and/or paradoxical response to dextroamphetamine. The findings indicate an acute and a probably long-term effect of dextroamphetamine and methylphenidate on the homeostasis of growth hormone. The possible long-term adverse effects of these drugs on the growth of children indicates the need for caution to the widespread use of these agents.

Adolescent↗
PubMed1977

The effect of L-dopa with and without decarboxylase inhibitor on growth hormone secretion in children with short stature.

The efficiency of L-dopa alone and L-dopa plus a dopa-decarboxylase inhibitor (carbidopa) in provoking growth hormome (GH) secretion was studied 40 children with short stature. By preventing the extracerebral metabolism, carbidopa increases the availability of L-dopa to the brain. The study was designed as paired series of growth hormone stimulation tests in which the effect of L-dopa alone, in different dosage schedules, was compared with the same dose level of L-dopa plus carbidopa, When L-dopa was given in full dose (125-500 mg), there was no significant difference in the serum GH concentrations at any time of sampling. In the lower dose level, the stimulant effect of L-dopa alone tended to be exceeded by the combination of L-dopa and carbidopa. The serum GH responses to the different schedules indicate that an optimal hypothalamic dopamine concentration for GH release could be achieved with a considerably lower dose of L-dopa than those employed in previously reported studies. When L-dopa is combined with a dopa decarboxylase inhibitor, the children have the advantage of less side effects in the form of nausea and vomiting.

Administration, Oral↗