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Biomedical subjects

P Vestergaard

Publications and source records attributed to P Vestergaard.

At least 73 records · Page 4Linked to original sources
PubMed2000

Hormonal replacement therapy reduces forearm fracture incidence in recent postmenopausal women - results of the Danish Osteoporosis Prevention Study.

OBJECTIVES: To study the fracture reducing potential of hormonal replacement therapy (HRT) in recent postmenopausal women in a primary preventive scenario. METHODS: Prospective controlled comprehensive cohort trial: 2016 healthy women aged 45-58 years, from three to 24 months past last menstrual bleeding were recruited from a random sample of the background population. Mean age was 50. 8+/-2.8 years, and the number of person years followed was 9335.3. There were two main study arms: a randomised arm (randomised to HRT; n=502, or not; n=504) and a non-randomised arm (on HRT; n=221, or not; n=789 by own choice). First line HRT was oral sequential oestradiol/norethisterone in women with intact uterus and oral continuous oestradiol in hysterectomised women. RESULTS: After five years, a total of 156 fractures were sustained by 140 women. There were 51 forearm fractures in 51 women. By intention-to-treat analysis (n=2016), overall fracture risk was borderline statistically significantly reduced (RR=0.73, 95% CI: 0.50-1.05), and forearm fracture risk was significantly reduced (RR=0.45, 95% CI: 0.22-0.90) with HRT. Restricting the analysis to women who had adhered to their initial allocation of either HRT (n=395) or no HRT (n=977) showed a significant reduction in both the overall fracture risk (RR=0.61, 95% CI: 0.39-0.97) and the risk of forearm fractures (RR=0.24, 95% CI: 0.09-0.69). Compliance with HRT was 65% after five years. CONCLUSIONS: It is possible to reduce the number of forearm fractures and possibly the total number of fractures in recent postmenopausal women by use of HRT as primary prevention.

Age Factors↗
PubMed2000

Cohort study of risk of fracture before and after surgery for primary hyperparathyroidism.

OBJECTIVES: To study whether fracture risk before and after surgery was increased in patients with primary hyperparathyroidism. DESIGN: Cohort study. SETTING: Three Danish university hospitals. PARTICIPANTS: 674 consecutive patients with primary hyperparathyroidism (median age 61, range 13-89 years) operated on during the period 1 January 1979 to 31 December 1997; 2021 age and sex matched controls from national patient register. MAIN OUTCOME MEASURE: Fractures. RESULTS: The cases had an increased relative rate of fractures compared with the controls before surgery (1.8, 95% confidence interval 1.3 to 2.3) but not after surgery (1.0, 0.8 to 1.3). The risk of fracture was increased for the vertebrae (3.5, 1.3 to 9.7), the distal part of the lower leg and ankles (2.3, 1.2 to 4.3), and the non-distal part of the forearm (4.0, 1.5 to 10.6) before surgery but not after. The increase in risk of fracture began about 10 years before surgery. Risk peaked 5-6 years before surgery and remained raised, although at a lower level, in the five years immediately before surgery. A small increase in risk of fracture of the distal forearm emerged more than 10 years after surgery (2.9, 1. 3 to 6.7). CONCLUSIONS: Risk of fracture is increased up to 10 years before surgery in patients with primary hyperparathyroidism. The risk returns to normal after surgery.

Adenoma↗
PubMed2000

Association and linkage studies of CRH and PENK genes in bipolar disorder: a collaborative IGSLI study.

Corticotropin-releasing hormone (CRH) and proenkephalin (PENK) are hypothalamic peptides involved in the stress response and hypothalamic-pituitary axis regulation. Previous research has implicated these peptides in the pathogenesis of affective disorders. In this study we investigated two polymorphisms located in the genes that code for CRH and PENK by means of association and linkage analyses. A total of 138 bipolar patients and 108 controls were included in the association study. In addition, 24 families were available for linkage analysis, including six families of probands with documented periodic positivity of dexamethasone suppression tests (DST) during remission. We found no association of bipolar disorder with either gene. Similarly, we did not find any evidence of linkage (P = 0.56 for CRH and 0.52 for PENK) in the entire sample or in the subsample of families of DST positive probands. In conclusion, our study does not support the hypothesis that genes coding for CRH or PENK contribute to the genetic susceptibility to bipolar disorder. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:178-181, 2000.

Adult↗
PubMed2000

Polyglutamine coding genes in bipolar disorder: lack of association with selected candidate loci.

BACKGROUND: Several studies have suggested that expanded trinucleotide repeats, particularly CAG, may have a role in the etiology of BD. Results obtained with the repeat expansion detection technique (RED) have indicated that bipolar patients have an excess of expanded CAG repeats. However, it is not clear which loci account for this difference. METHODS: Using lithium-responsive bipolar patients in order to reduce heterogeneity, we investigated five loci that are expressed in the brain and contain translated CAG repeats. A sample of 138 cases and 108 controls was studied. Genotypes were coded quantitatively or qualitatively and repeat distributions were compared. RESULTS: No difference was found in allele distribution between cases and controls for any of the loci studied. In one locus - L10378 - patients had a tendency to present shorter alleles (28.1 versus 27.9 repeats; t=2.55, df=205, P=0.011), however, this difference disappeared after correction for multiple testing. LIMITATIONS: The study has limitations common to most candidate gene association studies, that is, limited number of loci investigated and limited power to detect loci that account for a small proportion of the total genetic variability. CONCLUSIONS: Our results suggest that the loci investigated have no major role in the genetic predisposition to bipolar disorder.

Adult↗
PubMed2000

Fractures in patients with primary idiopathic hypothyroidism.

AIM: To study fracture risk and risk factors for fractures in patients with primary idiopathic hypothyroidism (ICD 10: E03.9). DESIGN: Historical follow-up. MATERIAL AND METHODS: A self-administered questionnaire was issued to 628 patients with primary idiopathic levothyroxine-substituted hypothyroidism. A total of 412 (65.6%) responded and of these, 408 could be analyzed. The 408 respondents were age- (+/- 5 years) and gender-matched with 408 normal controls randomly selected from the background population who responded to the same questionnaire. RESULTS: Overall fracture risk was increased in patients compared to controls (relative risk: RR = 1.6, 95% CI: 1.0-2.5). However, the increase was temporary and limited to the period within the first 2 years after the diagnosis of hypothyroidism (RR = 3.1, 95% CI: 1.4-7.0). Before the diagnosis and more than 2 years after the diagnosis, the fracture risk in patients did not deviate from that of the controls. The increase in fracture risk was only significant in the age group above 50 years (RR = 1.8, 95% CI: 1-3.2), and was limited to the forearms (RR = 3.0, 95% CI: 1.4-6.3 for the entire patient population). CONCLUSIONS: There was a temporary increase in fracture risk within the first 2 years after diagnosis of primary idiopathic hypothyroidism. The fracture risk was mainly increased in the age group above 50 years, and the increased risk was limited to the forearms.

Adult↗
PubMed2000

Fracture risk in patients treated for hyperthyroidism.

AIM: To study fracture risk and risk factors for fractures in patients with hyperthyroidism. DESIGN: Historical follow-up. MATERIAL AND METHODS: A total of 864 patients with diffuse toxic goiter (ICD 10: E05.0) or toxic nodular goiter (E05.2) were contacted through a self-administered questionnaire. Each respondent was compared to an age: (+/- 5 years) and gender-matched control from a random sample of the background population who responded to the same questionnaire. RESULTS: Among the patients 621 (72%) responded and of these 617 could be analyzed. Within the first 5 years before the diagnosis, the patients had the same fracture risk as the controls (RR = 1.2, 95% CI; 0.7-2.0). After the diagnosis, fracture risk was elevated among the patients (RR = 1.7, 95% CI: 1.2-2.3), especially in the age group 50 years or older (RR = 2.2, 95% CI: 1.5-3.3). Fracture risk was elevated for fractures of the spine (RR = 8.9, 95% CI: 1.6-48.4), and the forearms (RR = 3.1, 95% CI: 1.6-6.2), but not at other skeletal sites. Treatment with radioactive iodine alone was associated with an increased fracture risk (OR = 2.7, 95% CI: 1.2-6.0), a risk that was not present in patients who, in addition to radioactive iodine, also had received methimazole (RR = 1.5, 95% CI: 0.7-3.2). CONCLUSIONS: Our study demonstrated an increased fracture risk in hyperthyroidism, a fracture risk that was present with radioactive iodine treatment alone, but not in subjects that had received both radioactive iodine and methimazole or other types of antithyroid therapy.

Adult↗
PubMed2000

Fracture risk is increased in Crohn's disease, but not in ulcerative colitis.

AIMS: To study fracture rates and risk factors for fractures in patients with Crohn's disease and ulcerative colitis. METHODS: 998 self administered questionnaires were issued to members of the Danish Colitis/Crohn Association, and 1000 questionnaires were issued to randomly selected control subjects. 845 patients (84.5%) and 645 controls (65.4%) returned the questionnaire (p<0.01). 817 patients and 635 controls could be analysed. RESULTS: Analysis was performed on 383 patients with Crohn's disease (median age 39, range 8-82 years; median age at diagnosis 26, range 1-75 years), 434 patients with ulcerative colitis (median age 39, range 11-86 years; median age at diagnosis 29, range 10-78 years), and 635 controls (median age 43, range 19-93 years, p<0.01). The fracture risk was increased in female patients with Crohn's disease (relative risk (RR) = 2.5, 95% confidence interval (CI) 1.7-3.6), but not in male patients with Crohn's disease (RR = 0.6, 95% CI 0.3-1.3) or in patients with ulcerative colitis (RR = 1.1, 95% CI 0.8-1.6). An increased proportion of low energy fractures was observed in patients with Crohn's disease (15.7% versus 1.4 % in controls, 2p<0. 01), but not in patients with ulcerative colitis (5.4%, 2p=0.30). The increased fracture frequency in Crohn's disease was present for fractures of the spine, feet, and toes and fractures of the ribs and pelvis. Fracture risk increased with increasing duration of systemic corticosteroid use in Crohn's disease (2p=0.028), but not in ulcerative colitis (2p=0.50). CONCLUSIONS: An increased risk of low energy fractures was observed in female patients with Crohn's disease, but not in male patients with Crohn's disease or in patients with ulcerative colitis.

Adolescent↗
PubMed2000

Sixteen-year mortality in patients with affective disorder commenced on lithium.

BACKGROUND: Lithium treatment is claimed to reduce mortality in patients with affective disorder, but the evidence is conflicting. AIM: To estimate mortality rates from a cohort of patients with affective disorder commenced on lithium with an observation period of two years and a follow-up after 16 years. METHOD: The mortality rates of patients were compared with those of the general Danish population, standardised for age, gender and calendar time with respect to death from all causes, suicide and death from cardiovascular disease. RESULTS: Forty of the study's 133 patients died during the 16-year observation period (11 from suicide). Mortality among patients commenced on lithium was twice that of the general population. The statistically significantly elevated mortality was due largely to an excess of suicides; mortality from all other causes was similar to the background populations. Thirty-two patients died after the first two years of observation and were included in the analysis of the association between death and treatment compliance. Suicide occurred more frequently among those patients not complying with treatment. CONCLUSION: Mortality, especially suicide, was significantly increased in unselected patients with affective disorder commenced on lithium relative to the general population.

Adult↗
PubMed2000

Diagnosis of growth hormone (GH) deficiency in adults with hypothalamic-pituitary disorders: comparison of test results using pyridostigmine plus GH-releasing hormone (GHRH), clonidine plus GHRH, and insulin-induced hypoglycemia as GH secretagogues.

The insulin tolerance test (ITT) is widely accepted as the method of choice to evaluate GH secretion capacity in adults with hypothalamic-pituitary disorders. However, the test is not suitable in the elderly or in patients with cardiovascular disease or seizure disorders. In recent years alternatives to the ITT have been introduced. The purpose of the present study was to investigate the diagnostic outcome with the ITT, the pyridostigmine plus GHRH (PD + GHRH) test, the clonidine plus GHRH (CLO+GHRH) test, and insulin-like growth factor I (IGF-I) in an unselected group of patients with hypothalamic-pituitary disease. An evaluation of the reproducibility of the different stimulation tests was included in the study. Based on repeated testing with the various GH stimulation tests in healthy adult males and females, the lower limits of normality for the ITT, the PD+GHRH test, and the CLO+GHRH test were 3.92, 12.8, and 19.0, microg/L, respectively. A consecutive group of 26 unselected patients with hypothalamic-pituitary disorders, 13 males and 13 females (median age, 44 ys), were tested twice with all stimulation tests, except that only 10 patients were tested once with the CLO+GHRH test due to side-effects related to clonidine. The peak GH responses between test 1 and test 2 correlated significantly in both the ITT and the PD + GHRH test (P < 0.02), and no significant difference was observed in the median peak response to repeated testing. In addition, no sex difference was observed. The coefficients of variation (CV) were 96% (ITT) and 45% (PD + GHRH), but in the majority of patients low values were repeatedly low. The peak GH response was significantly higher during the PD+GHRH test than during the ITT (P = 0.008). In the 10 patients tested with the PD+GHRH and CLO+GHRH tests there was no significant difference in the peak GH response (P = 0.398). When the test specific cut-off values were used, no significant difference in diagnostic outcome was observed between the various tests (P > 0.3). In contrast, the diagnosis obtained with IGF-I differed significantly from all GH stimulation tests (P < 0.03). Twenty (77%) and 22 (85%) patients were diagnosed to be GH deficient with the ITT and the PD+GHRH test, respectively. Of the 14 patients with multiple pituitary failure (>2 hormones affected), GH deficiency was present in more than 90% regardless of the type of stimulation test used. The IGF-I levels were only subnormal in 42% of the patients and did not correlate with the peak GH responses in any of the stimulation tests (P > 0.05). Except for 1 patient all patients with subnormal IGF-I were GH deficient in all stimulation tests. It is concluded that in patients with hypothalamic-pituitary disease and a normal IGF-I level 2 stimulation tests should be performed to establish a diagnosis of GH deficiency. In patients with a subnormal IGF-I value a single GH stimulation test should be sufficient to confirm the presence of GH deficiency.

Adult↗
PubMed2000

Artifact in bone mineral measurements during a very low calorie diet: short-term effects of growth hormone.

Short-term effects of growth hormone on bone metabolism and soft tissue collagen metabolism during weight loss in obese subjects on a very low calorie diet were investigated in a double-blind, placebo-controlled design. Twenty healthy obese women (BMI between 33 and 45 kg/m(2)) aged 21-48 yr were followed for 8 wk: half received growth hormone. A 740-kcal diet was administered the first 4 wk, followed by a 1200-kcal diet. Lumbar spine BMC, total-body fat mass, total-body lean body mass, total-body BMC, and total-body bone area were measured by dual-energy X-ray absorptiometry along with biochemical markers of bone turnover. Body weight decreased by 5.5% and fat mass by 11.4%. There were no changes in biochemical bone markers in the placebo group despite a marked decrease in BMC (3.1%). Projected total bone area decreased proportional to BMC (r = 0.89) during the weight loss. Growth hormone treatment did not modulate the decrease in lean body mass, body weight, fat mass, or BMC, but increased bone turnover markers. Growth hormone did not change the results concerning BMC, projected bone area, BMD, lean body mass or fat mass. Since 89% of the observed change in BMC could be explained by alterations in projected bone area without changes in biochemical bone markers, it is concluded that a large part of the observed decrease in BMC during weight loss may be due to scanner artifact.

Absorptiometry, Photon↗
PubMed2000

Association and linkage studies of candidate genes involved in GABAergic neurotransmission in lithium-responsive bipolar disorder.

OBJECTIVE: To test for genetic linkage and association with GABAergic candidate genes in lithium-responsive bipolar disorder. DESIGN: Polymorphisms located in genes that code for GABRA3, GABRA5 and GABRB3 subunits of the GABAA receptor were investigated using association and linkage strategies. PARTICIPANTS: A total of 138 patients with bipolar 1 disorder with a clear response to lithium prophylaxis, selected from specialized lithium clinics in Canada and Europe that are part of the International Group for the Study of Lithium-Treated Patients, and 108 psychiatrically healthy controls. Families of 24 probands were suitable for linkage analysis. OUTCOME MEASURES: The association between the candidate genes and patients with bipolar disorder versus that of controls and genetic linkage within families. RESULTS: There was no significant association or linkage found between lithium-responsive bipolar disorder and the GABAergic candidate genes investigated. CONCLUSIONS: This study does not support a major role for the GABAergic candidate genes tested in lithium-responsive bipolar disorder.

Alleles↗
PubMed1999

[Costs of different intervention strategies to prevent hip fractures].

The cost of primary prevention and the number of hip fractures prevented was compared in different scenarios. Primary prevention with hormonal replacement therapy (HRT) in women over the age of 50 years, secondary prevention with HRT in women over 50 years with low bone mineral on screening, use of external hip protectors in nursing home residents, use of calcium and vitamin D in nursing home residents and tertiary prevention with bisphosphonates (alendronate) or external hip protectors in subjects with a previous hip fracture were evaluated. External hip protectors or calcium plus vitamin D were cheap in nursing home residents. The economic cost of bisphosphonate treatment was high even in tertiary prevention in the high risk group with previous hip fracture. It was doubtful whether potential savings in prevention would out-weigh the cost in younger individuals even in high-risk groups.

Adult↗
PubMed1999

Dependence of cadmium-metallothionein nephrotoxicity on glutathione.

Acute cadmium-metallothionein (CdMT) injection is frequently used as a model to study the mechanism of chronic Cd-induced nephrotoxicity. The purpose of this study was to investigate the relationship between glutathione (GSH) status and the ability of CdMT, either administered as a bolus dose or infused over a 24-h period by an osmotic minipump, to cause nephrotoxicity. GSH levels were modulated by pretreatment with either buthionine sulfoximine (BSO) or GSH. BSO enhanced while GSH suppressed acute CdMT nephrotoxicity. An infused dose of CdMT (150 microg Cd/kg) that was well tolerated when delivered over a 24-h period became nephrotoxic when GSH synthesis was inhibited by BSO. With depletion of GSH, as little as 0.4 microg Cd/g renal cortex was sufficient to cause nephrotoxicity after an acute dose of CdMT. While BSO had no effect on renal Cd accumulation, pretreatment with GSH reduced renal cortical Cd accumulation by 36%. CdMT nephrotoxicity was enhanced by depleting renal GSH, but without increasing renal Cd accumulation, which suggests that intracellular GSH is directly involved in protection against CdMT nephrotoxicity. Reduced Cd accumulation in the renal cortex following GSH pretreatment suggests an additional extracellular mechanism of GSH protection. It is concluded that GSH status is an important determinant of CdMT nephrotoxicity, with low GSH levels enhancing and high GSH levels reducing its toxicity, and that the mechanism appears to involve both intracellular and extracellular sites.

Animals↗