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Biomedical subjects

Henrik Vestergaard

Publications and source records attributed to Henrik Vestergaard.

14 recordsLinked to original sources

[Mediastinal parathyroid cystadenoma--a rare cause of primary hyperparathyroidism].

Parathyroid cysts located in the mediastinum are rare. They may be non-functioning or associated with primary hyperparathyroidism (PHPT). We present a patient with persistent PHPT despite previous parathyroid surgery. Parathyroid scintigraphy with 99mTc sestamibi showed no focus with radioactivity retention, but MRI revealed a large parathyroid cystadenoma in the mediastinum, which was successfully removed. In general, MRI is not the first choice for parathyroid imaging, but when the adenoma is localized at ectopic sites, MRI is a good imaging modality.

Aged↗

Serum ionised calcium and cardiovascular disease in 45-years old men and women followed for 18 years.

UNLABELLED: High level of total serum calcium within the normal range has been associated with increased cardiovascular risk. We wanted to evaluate whether the physiological active ionised form of calcium also was a risk factor for cardiovascular disease (CVD). METHODS: A total of 974 participants from a health survey in 1981 in Copenhagen had ionised serum calcium and different cardiovascular risk factors measured. The participants were followed until 1999 in The National Hospital Patients Registry and The National Death Registry in Denmark regarding the diagnosis ischemic heart disease (IHD) and a broader definition of CVD. Persons with ionised serum calcium in the highest quintile were compared with persons in the lower four quintiles. RESULTS: In a univariate analysis persons with ionised serum calcium in the highest quintile had increased risk of IHD (p=0.001) and CVD (p=0.02) compared to persons in the lower quintiles. The increased risk disappeared when gender and cardiovascular confounders were included in a Cox proportional hazards analysis (p=0.20 for IHD and p=0.50 for CVD, respectively). In a separate analysis of men and IHD the result remained insignificant (p=0.07). CONCLUSIONS: Serum ionised calcium in the upper quintile in women and men together did not seem to be a risk factor in development of IHD and CVD, but a non-significant tendency towards increased risk of IHD was observed in men with ionised calcium in the upper quintile compared to men in the lower four quintiles.

Calcium↗

IRS-1 serine phosphorylation and insulin resistance in skeletal muscle from pancreas transplant recipients.

Insulin-dependent diabetic recipients of successful pancreas allografts achieve self-regulatory insulin secretion and discontinue exogenous insulin therapy; however, chronic hyperinsulinemia and impaired insulin sensitivity generally develop. To determine whether insulin resistance is accompanied by altered signal transduction, skeletal muscle biopsies were obtained from pancreas-kidney transplant recipients (n = 4), nondiabetic kidney transplant recipients (receiving the same immunosuppressive drugs; n = 5), and healthy subjects (n = 6) before and during a euglycemic-hyperinsulinemic clamp. Basal insulin receptor substrate (IRS)-1 Ser (312) and Ser (616) phosphorylation, IRS-1-associated phosphatidylinositol 3-kinase activity, and extracellular signal-regulated kinase (ERK)-1/2 phosphorylation were elevated in pancreas-kidney transplant recipients, coincident with fasting hyperinsulinemia. Basal IRS-1 Ser (312) and Ser (616) phosphorylation was also increased in nondiabetic kidney transplant recipients. Insulin increased phosphorylation of IRS-1 at Ser (312) but not Ser (616) in healthy subjects, with impairments noted in nondiabetic kidney and pancreas-kidney transplant recipients. Insulin action on ERK-1/2 and Akt phosphorylation was impaired in pancreas-kidney transplant recipients and was preserved in nondiabetic kidney transplant recipients. Importantly, insulin stimulation of the Akt substrate AS160 was impaired in nondiabetic kidney and pancreas-kidney transplant recipients. In conclusion, peripheral insulin resistance in pancreas-kidney transplant recipients may arise from a negative feedback regulation of the canonical insulin-signaling cascade from excessive serine phosphorylation of IRS-1, possibly as a consequence of immunosuppressive therapy and hyperinsulinemia.

Adult↗

Myocardial perfusion defects and the left ventricular ejection fraction disclosed by scintigraphy in patients with primary hyperparathyroidism.

Patients with primary hyperparathyroidism (PHPT) have increased risk of cardiovascular disease. For patients undergoing preoperative parathyroid imaging with 99mTc-sestamibi single photon emission computed tomography (SPECT), we combined cervical SPECT and gated cardiac SPECT to achieve information about the localization of parathyroid adenomas, myocardial perfusion, and the left ventricular ejection fraction (LVEF) at rest. A series of 22 patients with PHPT and no history of myocardial infarction or angina pectoris were recruited consecutively. At 60 minutes after injection of 700 MBq 99mTc-sestamibi, SPECT of the neck and gated myocardial perfusion SPECT were performed at the same time. All of the patients who underwent parathyroidectomy had the parathyroid adenoma localized as predicted from the SPECT. Five patients (23%) had myocardial perfusion defects extending more than 15% (range 15-25%), and they had higher plasma parathyroid hormone levels (p = 0.03), and lower LVEF (p = 0.007) than patients without perfusion defects. We suggest that patients with hyperparathyroidism and suspected cardiovascular disease can undergo 99mTc-sestamibi parathyroid SPECT simultaneously with gated myocardial perfusion SPECT to obtain information about the resting perfusion status and cardiac systolic function. The results from myocardial perfusion SPECT can lead to initiation of cardiovascular treatment and eventually perioperative precautions.

Adenoma↗

Increased plasma N-terminal pro-B-type natriuretic peptide and markers of inflammation related to atherosclerosis in patients with primary hyperparathyroidism.

OBJECTIVE: Increased risk of cardiovascular disease has been reported in patients with primary hyperparathyroidism (PHPT). The aim of this study was to evaluate novel plasma risk markers of cardiovascular disease in patients with PHPT. DESIGN: PHPT patients were evaluated with a control group. Patients who underwent parathyroidectomy were re-evaluated after 7 and 18 months. PATIENTS: Forty-five PHPT patients and 40 matched controls participated. Seventeen patients underwent parathyroidectomy. MEASUREMENTS: Plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity C-reactive protein (CRP), interleukin-6 (IL-6) and tumour necrosis factor alpha (TNF-alpha), lipids and blood pressure were measured. In 27 patients a bicycle exercise test and radionuclide angiography were performed, and repeated in those who underwent parathyroidectomy. RESULTS: Plasma NT-proBNP, CRP and TNF-alpha, but not IL-6, were higher in patients with PHPT than in controls (P < 0.01 and P = 0.17, respectively). In patients with PHPT, NT-proBNP correlated with systolic blood pressure, left ventricular end-diastolic volume, and peak oxygen uptake (all P < 0.01). Log CRP correlated with systolic and diastolic blood pressure (both P < 0.05) and log IL-6 (P < 0.01). No significant correlations were observed between PTH or calcium and risk markers of cardiovascular disease. No decrease in NT-proBNP, markers of inflammation or blood pressure was observed after parathyroidectomy. CONCLUSIONS: Our data suggest that hypertension or other factors, rather than plasma calcium or PTH, could explain the increased levels of the inflammatory markers and NT-proBNP in PHPT. We therefore suggest that aggressive treatment of hypertension should be initiated in patients with PHPT to try to reduce the increased cardiovascular mortality described in PHPT. Further prospective studies are needed to validate the suggestion that increased levels of NT-proBNP and inflammatory markers also represent strong prognostic markers of cardiovascular disease in patients with PHPT.

Absorptiometry, Photon↗

Parathyroid scintigraphy during hypocalcaemia in primary hyperparathyroidism.

BACKGROUND: Minimally invasive parathyroid surgery in patients with primary hyperparathyroidism (PHPT) demands high imaging accuracy. By increasing blood flow to the parathyroid adenoma before injection of a perfusion marker, we intended to improve the parathyroid scintigraphy. We have named the technique stimulated parathyroid scintigraphy (SPS). METHODS: Twenty minutes after injection of 100 MBq (99m)Tc-pertechnetate a thyroid scintigram was performed in 25 patients with PHPT. During the thyroid scintigraphy sodium citrate was infused which lowered plasma calcium by a mean of 14 +/- 1.3%. Then 700 MBq (99m)Tc-sestamibi was injected and another scintigram of the neck was obtained. Perchlorate was given at the end of the sestamibi scintigram to increase the wash-out of (99m)Tc-pertechnetate from the thyroid gland, and after 2 h a delayed scintigram was obtained. A subtraction of the thyroid scintigram from the initial sestamibi scintigram was performed. The results of SPS and a conventional (99m)Tc-sestamibi dual-phase parathyroid scintigraphy were compared with the operative findings. In nine patients the parathyroid adenoma was also localized with ultrasound and the flow pattern before and after citrate infusion was visualized with Doppler technique. RESULTS: Eighty-eight per cent of the adenomas were localized correctly with the SPS technique compared with 62% at the conventional parathyroid scintigraphy. Tissue perfusion of the nine adenomas increased after citrate infusion. CONCLUSIONS: SPS has a high accuracy and it is easy to perform. If only subtraction SPS is performed the whole examination can be completed within an hour, which is acceptable for same day surgery.

Adenoma↗

The independent effect of type 2 diabetes mellitus on ischemic heart disease, stroke, and death: a population-based study of 13,000 men and women with 20 years of follow-up.

BACKGROUND: Epidemiological studies have reported that patients with type 2 diabetes mellitus (DM) have increased mortality and morbidity from cardiovascular diseases, independent of other risk factors. However, most of these studies have been performed in selected patient groups. The purpose of the present study was prospectively to assess the impact of type 2 DM on cardiovascular morbidity and mortality in an unselected population. METHODS: A total of 13,105 subjects from the Copenhagen City Heart Study were followed up prospectively for 20 years. Adjusted relative risks of first, incident, admission for, or death from ischemic heart disease, acute myocardial infarction, or stroke, as well as total mortality in persons with type 2 DM compared with healthy controls, were estimated. RESULTS: The relative risk of first, incident, and admission for myocardial infarction was increased 1.5- to 4.5-fold in women and 1.5- to 2-fold in men, with a significant difference between sexes. The relative risk of first, incident, and admission for stroke was increased 2- to 6.5-fold in women and 1.5- to 2-fold in men, with a significant difference between sexes. In both women and men the relative risk of death was increased 1.5 to 2 times. CONCLUSIONS: In persons with type 2 DM, the risk of having an incident myocardial infarction or stroke is increased 2- to 3-fold and the risk of death is increased 2-fold, independent of other known risk factors for cardiovascular diseases.

Age Factors↗

Increasing incidence of diabetes after gestational diabetes: a long-term follow-up in a Danish population.

OBJECTIVE: To study the incidence of diabetes among women with previous diet-treated gestational diabetes mellitus (GDM) in the light of the general increasing incidence of overweight and diabetes and to identify risk factors for the development of diabetes. RESEARCH DESIGN AND METHODS: Women with diet-treated GDM during 1978-1985 (old cohort, n = 241, also followed up around 1990) or 1987-1996 (new cohort, n = 512) were examined in 2000-2002. Women were classified by a 2-h, 75-g oral glucose tolerance test according to the World Health Organization criteria or an intravenous glucagon test supplemented by measurement of GAD antibodies. Historical data from index-pregnancy and anthropometrical measurements were collected. RESULTS: A total of 481 (63.9%) women were examined (median 9.8 years [interquartile range 6.4-17.2]) after index pregnancy. Diabetes and impaired glucose tolerance (IGT)/impaired fasting glucose were present in 40.0 and 27.0% of women, respectively. In the new cohort, 40.9% had diabetes compared with 18.3% in the old cohort at the 1990 follow-up (P < 0.0005). Prepregnancy BMI was significantly higher in the new compared with the old cohort (26.0 [22.5-30.8] vs. 22.9 kg/m2 [20.2-28.0], P < 0.0005). Among others, new-cohort membership, prepregnancy overweight (BMI > or = 25 kg/m2), and IGT postpartum were identified as independent predictors of diabetes by multiple logistic regression analyses. CONCLUSIONS: The incidence of diabetes among Danish women with previous diet-treated GDM was very high and had more than doubled over a 10-year period. This seems to be due to a substantial increase in BMI in women with GDM.

Adult↗

Increased mortality in patients hospitalized with primary hyperparathyroidism during the period 1977-1993 in Denmark.

The aim of the present study was to determine whether patients with the incident hospital diagnosis of primary hyperparathyroidism (PHPT) in Denmark during the period 1977-1993 had an increased mortality from cardiovascular disease and cancer compared to the rest of the Danish population. In a random sample of half of the Danish population, all patients with an incident hospital diagnosis of PHPT were identified in the National Hospital Patients Register. The mortality in the cohort was analyzed and compared with the background population. A cohort of 1578 patients was identified. Follow-up of 1179 women and 376 men, who did not die in the same month as the incident PHPT diagnosis, was made through 1993. Of these, 312 (20%) died within the follow-up period. The standard mortality ratio (SMR) for women was 1.7 (95% confidence interval [95% CI]: 1.5-1.9). SMR for men was 1.6 (95% CI: 1.3-2.0). In women an increased mortality from ischemic heart disease, cerebrovascular disease, and cancer was found. In men an increased mortality from cerebrovascular disease and cancer was found.

Cardiovascular Diseases↗

Insulin resistance and maximal oxygen uptake.

BACKGROUND: Type 2 diabetes, coronary atherosclerosis, and physical fitness all correlate with insulin resistance, but the relative importance of each component is unknown. HYPOTHESIS: This study was undertaken to determine the relationship between insulin resistance, maximal oxygen uptake, and the presence of either diabetes or ischemic heart disease. METHODS: The study population comprised 33 patients with and without diabetes and ischemic heart disease. Insulin resistance was measured by a hyperinsulinemic euglycemic clamp; maximal oxygen uptake was measured during a bicycle exercise test. RESULTS: There was a strong correlation between maximal oxygen uptake and insulin-stimulated glucose uptake (r = 0.7, p = 0.001), and maximal oxygen uptake was the only factor of importance for determining insulin sensitivity in a model, which also included the presence of diabetes and ischemic heart disease. CONCLUSION: Maximal oxygen uptake may be a more important determinant for insulin sensitivity than ischemic heart disease and type 2 diabetes.

Diabetes Mellitus, Type 2↗

Normocalcemia and persistent elevated serum concentrations of 1-84 parathyroid hormone after operation for sporadic parathyroid adenoma: evidence of increased morbidity from cardiovascular disease.

Elevated serum concentrations of 1-84 parathyroid hormone (PTH) after operation for sporadic parathyroid adenoma have been reported in previous studies, years after operation for primary hyperparathyroidism (pHPT). The cause and significance of this finding have not been elucidated. Primary hyperparathyroidism was diagnosed in 195 patients from January 1987 to December 1998. Operation for pHPT was performed in 124 patients. To evaluate long-term effects of elevated serum 1-84 PTH, biochemical variables and pre- and postoperative diseases were investigated from hospital case records. Of the 124 patients operated on, 103 had a solitary adenoma. Among these patients, 60 had normal serum concentrations of 1-84 PTH and calcium postoperatively, 38 patients had follow-up for more than 12 months (range 12-207 months-group A). Persistent elevated serum concentrations of 1-84 PTH and normocalcemia were found in 23 patients. Fourteen patients had follow-up for more than 12 months (range 15-76 months-group B). Two patients had persistent pHPT, and 18 were normocalcemic, but in this retrospective study data on serum 1-84 PTH were not available. No significant differences were found between groups A and B at the time of diagnosis concerning clinical characteristics. More that 12 months after operation for pHPT, the patients in group B, with persistent elevated serum concentrations of 1-84 PTH, had a significantly (c2 = 11, p = 0.005, and power of test 0.66) higher frequency of cardiovascular diseases from ischemic heart disease and hypertension. Persistent elevated serum concentrations of 1-84 PTH after operation for sporadic parathyroid adenoma may be associated with development of cardiovascular disease. This group of patients therefore needs lifelong control and, possibly, medical intervention.

Adenoma↗

A P387L variant in protein tyrosine phosphatase-1B (PTP-1B) is associated with type 2 diabetes and impaired serine phosphorylation of PTP-1B in vitro.

In the present study, we tested the hypothesis that variability in the protein tyrosine phosphatase-1B (PTP-1B) gene is associated with type 2 diabetes. Using single-strand conformational polymorphism analysis, we examined cDNA of PTP-1B from 56 insulin-resistant patients with type 2 diabetes as well as cDNA from 56 obese patients. Four silent variants, (NT CGA-->CGG) R199R, (NT CCC-->CCT) P303P, 3'UTR+104insG, and 3'UTR+86T-->G, and one missense variant, P387L, were found. Subsequent analysis on genomic DNA revealed two intron variants, IVS9+57C-->T and IVS9+58G-->A, and two missense variants, G381S and T420M. The G381S and 3'UTR+104insG insertion variants were not associated with type 2 diabetes. In an association study, the P387L variant was found in 14 of 527 type 2 diabetic subjects (allelic frequency 1.4%, 0.4-2.4 CI) and in 5 of 542 glucose-tolerant control subjects (allelic frequency 0.5%, CI 0.1-1.1), showing a significant association to type 2 diabetes (P = 0.036). In vitro, p34 cell division cycle (p34(cdc2)) kinase-directed incorporation of [gamma-(32)P]ATP was reduced in a mutant peptide compared with native peptide (387P: 100% vs. 387L: 28.4 +/- 5.8%; P = 0.0012). In summary, a rare P387L variant of the PTP-1B gene is associated with a 3.7 (CI 1.26-10.93, P = 0.02) genotype relative risk of type 2 diabetes in the examined population of Danish Caucasian subjects and results in impaired in vitro serine phosphorylation of the PTP-1B peptide.

Amino Acid Substitution↗