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Biomedical subjects

H Dige-Petersen

Publications and source records attributed to H Dige-Petersen.

At least 37 records · Page 2Linked to original sources

Basal insulin-level oscillations in normotensive individuals with genetic predisposition to essential hypertension exhibit an irregular pattern.

BACKGROUND: Insulin is secreted in regular pulses at intervals of 12-14 min in normal fasting subjects. An abnormal pattern has been found in subjects with non-insulin-dependent diabetes mellitus (NIDDM) and in young individuals predisposed to NIDDM. It has been suggested that there might be a causal relationship between insulin-secretion abnormalities and insulin resistance. OBJECTIVE: To examine whether insulin-secretion abnormalities are also present in offspring of patients with essential hypertension. METHODS: Eleven young (aged 18-35 years) normotensive individuals each of whom had two parents with essential hypertension were compared with 10 age- and sex-matched controls each of whom had two normotensive parents. We verified that diabetes and morbid obesity were absent among the subjects and their parents. We studied basal insulin-secretion patterns during a 60 min period, glucose tolerance by administering an oral glucose-tolerance test, insulin resistance by using an isoglycaemic hyperinsulinaemic clamp and basal plasma catecholamine levels. RESULTS: Autocorrelation analysis of insulin concentrations showed that the hypertension-prone subjects had a significantly reduced or irregular oscillatory pattern compared with the regular insulin-level oscillations with a period of 12-14 min in control subjects. The hypertension-prone subjects had significantly higher systolic blood pressures and tended to be insulin-resistant. CONCLUSION: This is the first evidence of early insulin-secretion abnormalities in young normotensive individuals with a genetic predisposition to essential hypertension, but with a normal glucose tolerance and without a genetic predisposition to NIDDM. Early insulin-secretion abnormalities may be the very first step towards the development of insulin resistance and an important factor initiating the hypertension in hypertension-prone individuals.

Adolescent↗

AT1 receptor blockade and the sympathoadrenal response to insulin-induced hypoglycemia in humans.

An important facilitating effect of angiotensin II on adrenal catecholamine release has been demonstrated in several species. To determine whether specific AT1 receptor blockade affects medullary epinephrine secretion and musculocutaneous norepinephrine release during insulin-induced hypoglycemia, 16 healthy volunteers received losartan vs. placebo followed by an intravenous insulin bolus and measurement of effect variables at short intervals for 150 min. AT1 receptor blockade was effective, as evidenced by substantially increased circulating renin and angiotensin II levels, a 60% inhibition of circulating aldosterone, and an 8.5% decrease of mean arterial pressure over time compared with placebo. Arterial glucose concentration fell to a nadir of 1.9 mM, arterial epinephrine concentration increased 23-fold, forearm musculocutaneous norepinephrine release increased 4-fold, heart rate increased 40%, and forearm blood flow increased 3-fold. All absolute values and the time course of these changes were independent of AT1 receptor blockade. It is concluded that a putative interaction between angiotensin II and the sympathoadrenal axis may not be mediated by AT1 receptors in humans.

Adrenal Medulla↗

No effect of beta-adrenergic blockade on hypoglycaemic effect of glucagon-like peptide-1 (GLP-1) in normal subjects.

GLP-1 administration decreases blood glucose levels in normal subjects and non-insulin-dependent diabetes mellitus patients and is therefore proposed as a treatment for diabetic hyperglycaemia. The glucose lowering effect of GLP-1 is glucose dependent and therefore self-limiting, but it is not known to which extent counterregulatory mechanisms participate in this. GLP-1 was infused i.v. into 8 healthy subjects after an overnight fast at a rate of 100 pmol kg-1 h-1 for 1 h with and without beta-adrenoceptor blockade (i.v. bolus of 5 mg propranolol followed by a continuous infusion of 0.08 mg min-1). In a control experiment, saline and propranolol were infused. Hepatic glucose production was measured and blood was analysed for plasma glucose, insulin, glucagon, catecholamines, and radioactivity. Plasma GLP-1 levels were similar on the two GLP-1 infusion days and resulted in: (1) a significant decrease in plasma glucose from 5.2 +/- 0.2 to 4.1 +/- 0.1 mmol l-1 with GLP-1/propranolol infusion, and from 5.2 +/- 0.1 to 4.0 +/- 0.1 mmol l-1 with GLP-1/saline infusion (NS); (2) a corresponding significant increase in plasma insulin from 58.0 +/- 6.3 to 144.5 +/- 22.3 pmol l-1 and from 61.7 +/- 6.4 to 148.2 +/- 34.0 pmol l-1, respectively (NS); (3) a significant decrease in plasma glucagon from 11.7 +/- 1.6 to 6.5 +/- 1.5 pmol l-1 and from 10.4 +/- 1.6 to 4.6 +/- 1.0 pmol l-1, respectively; (4) a significant decrease in the rate of glucose appearance which was not significantly different on the two GLP-1 infusion days; and (5) an increase in catecholamine levels in the GLP-1/saline experiment and also in the beta-blockade experiments. We conclude that adrenergic counterregulation plays an insignificant role in curtailing GLP-1's glucose lowering effect.

Adrenergic beta-Antagonists↗

[Adrenogenital syndrome--diagnosis, treatment and therapeutic control].

Congenital adrenal hyperplasia is a rare, genetic disorder. In Denmark about 90 cases have been diagnosed over the last 20 years. It is potentially life-threatening in early childhood, and must be intensively controlled in order to achieve a normal growth, pubertal maturation and fertility. This article reviews the pathogenesis and genetic and clinical characteristics underlying congenital adrenal hyperplasia, and outlines pre- and postnatal approaches to the diagnosis and monitoring, with special emphasis on 21-hydroxylase defect.

Adrenal Hyperplasia, Congenital↗

Changes in left and right ventricular performance and volumes in seven-year survivors of acute myocardial infarction.

We describe the spontaneous long-term changes in right (RV) and left (LV) ventricular performance during a 7-year period after acute myocardial infarction (AMI). Radionuclide ventriculography was performed in the second week after AMI in 201 patients. RV and LV ejection fractions, and LV end-diastolic and end-systolic volumes were determined. A follow-up after 7 years was performed in 55 survivors. Of these, 16 patients were also examined after 1 year. During the 7-year follow-up period, LV ejection fraction decreased from 0.49 to 0.45 (p < 0.01). LV end-diastolic volume increased from 161 to 210 ml (30%) (p < 0.01), and LV end-systolic volume from 83 to 123 ml (48%) (p < 0.01). In patients without recurrent AMI, coronary artery bypass grafting surgery, or angiotensin-converting enzyme inhibitor therapy (n = 37) during follow-up, no change in average LV ejection fraction was observed. Nevertheless, this subgroup had substantial increases in LV end-diastolic volume, from 157 to 190 ml (21%) (p = 0.002) and in LV end-systolic volume, from 80 to 105 ml (31%) (p < 0.001). In a subgroup of patients also reinvestigated after 1 year (n = 16), there was a 15% increase in LV end-diastolic volume the first year after AMI with an additional 10% increase in LV end-diastolic volume between years 1 and 7. Corresponding figures for LV end-systolic volume were 20% and 12%, respectively. Hardly any association was apparent between LV ejection fraction, LV end-diastolic volume, and LV stroke volume at discharge for subsequent LV dilatation.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

The importance of adrenaline, insulin and insulin sensitivity as determinants for blood pressure in young Danes.

OBJECTIVE: To study the influence of the adrenergic system, fasting serum insulin level and insulin sensitivity on systolic (SBP) and diastolic blood pressure (DBP) in young individuals. DESIGN AND METHODS: In a population survey we measured SBP and DBP (using the London School of Hygiene sphygmomanometer) and fasting levels of serum catecholamines, serum insulin and insulin sensitivity in 383 randomly recruited subjects (mean age 25.0 years) of both sexes. Insulin sensitivity was estimated from a combined intravenous glucose and tolbutamide tolerance test and calculated using Bergman's minimal model. Confounders were body mass index, waist:hip ratio, maximal aerobic capacity, age, sex, and consumptions of tobacco and alcohol. RESULTS: In a multiple regression analysis including the above factors, the most important determinant of SBP, after sex, was the plasma adrenaline level (partial correlation coefficient, rp = 0.23, P < 0.01). No significant association was found between plasma noradrenaline level and SBP. A significant association was found between plasma adrenaline level and DBP in females only (rp = 0.15, P < 0.05). Overall, the plasma adrenaline level was more important than the plasma noradrenaline level. Fasting serum insulin level and insulin sensitivity were each significantly correlated with both SBP and DBP in univariate analyses, but not in a multiple regression analysis. A family history of hypertension was associated with higher SBP level, body mass index and fasting serum insulin level, and with lower insulin sensitivity, but with no difference in circulating plasma adrenaline or noradrenaline compared with individuals without a family history. In a multiple regression analysis with the above confounders, no significant association between SBP and plasma adrenaline level could be found in either sex for subjects with a family history of hypertension. Both male (rp = 0.41, P < 0.001) and female (rp = 0.18, P < 0.05) subjects with no history of family hypertension had a significant association between SBP and plasma adrenaline level in a multiple regression analysis. CONCLUSION: In young healthy Caucasians adrenergic activity is an important determinant for SBP. The importance of fasting serum insulin level and insulin sensitivity on blood pressure level is minor when confounders are considered.

Adolescent↗

Direct and quantitative vitamin B12 absorption measurement in patients with disorders in the distal part of the bowel. Comparison of stool spot test [SST] with whole body counting in patients with ileal pelvic reservoir, ileostomy or Crohn's disease.

Direct and quantitative vitamin B12 absorption studies were performed in 25 patients with disorders in the distal small intestine using whole body counting as the gold standard. Simultaneously, vitamin B12 absorption was also determined by the more simple stool spot test (SST) which incorporates 51CrCl3 as a nonabsorbable marker. The SST provided a reliable direct and quantitative measure of vitamin B12 absorption in patients with previous ileal resections due to Crohn's disease (CD) (n = 7) as compared with whole body counting. In ulcerative colitis (UC) patients with either an ileal pelvic reservoir (n = 10) or a conventional ileostomy (n = 8), markedly shorter bowel transit times and absence of colon may have hindered sufficient mixture of the tracer and marker isotopes which could explain the false absorption values according to the SST in single patients. Therefore, an intact colon and a near-normal bowel transit time seem to be essential for performance of the SST. Whole body counting showed, as expected, that all CD patients except one had decreased vitamin B12 absorption (median 23%; range 3-39%) (normally > 35%). In UC patients with ileostomy, only one had a markedly decreased vitamin B12 absorption, two borderline normal values, while the rest had normal values (median 54%, range 15-76%). All UC patients with ileal pelvic reservoir had normal vitamin B12 absorption values (median 40.5%, range 36-87%). We conclude that vitamin B12 substitution therapy is probably required in patients with CD with ileal resection.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Endothelin release and enhanced regional myocardial ischemia induced by cold-air inhalation in patients with stable angina.

This study was designed to determine the influence of cold-air inhalation on regional myocardial perfusion in patients with ischemic heart disease. A selected group of vasoactive hormones was measured to investigate their possible roles as ischemic agents. Ten men who had recently had a myocardial infarction and anginal symptoms and with verified pathologic ST deviations during a preceding exercise test volunteered to participate in this randomized cross-over study. Two identical exercise tests were performed on different days; one with inhalation of cold (-22 degrees C) air and the other one with inhalation of thermoneutral air (22 degrees C). Scintigraphic imaging (single-photon emission computed tomography) of regional myocardial blood flow was performed with technetium 99m isonitrile flowtracer and a Bull's eye visual display with calculation of the scintigraphic ischemic severity score. The score was significantly higher during exercise with inhalation of cold air as compared to exercise with inhalation of thermoneutral air. Furthermore, only with cold-air inhalation did arterial plasma endothelin concentration increase significantly from rest to exercise and correlate with the change of ischemic severity score. In contrast, no change was observed under thermoneutral conditions. There was no significant difference between peak values of heart rate, systolic blood pressure, adrenaline, and noradrenaline concentrations in the two situations. We conclude that inhalation of cold air during exercise increases the degree of regional myocardial ischemia and that this is not caused by an increased myocardial oxygen demand. We suggest that cold air directly influences the vasomotor tone of the myocardial resistance vessels and that endothelin may be involved in the ischemic response.

Adult↗

Neuroendocrine tests in depressive stroke patients.

1. In the present study 63 stroke patients and 23 control patients participated. The presence and degree of depression was defined by the Hamilton Rating Scale for Depression and the Research Diagnostic Criteria. 2. The TRH stimulation test was performed in all the patients. 3. No difference in Delta Max TSH was found between stroke patients and control patients. 4. No difference in Delta Max TSH was found between patients with the lesion in the right or left hemisphere. 5. No correlation was found between the frequency of blunted response to the TRH stimulation test and the presence of depression. 6. No difference in Delta Max TSH was found between suppressors and non-suppressors to the DST.

Adult↗

Effect of 1 or 2 MAC isoflurane with or without ketanserin on cerebral blood flow autoregulation in man.

We have studied the effect of 1 or 2 MAC isoflurane with or without ketanserin on cerebral blood flow (CBF), cerebral oxygen metabolism (CMRO2) and CBF autoregulation in 20 adult patients undergoing lumbar disc surgery. Ten patients received ketanserin and 10 isotonic saline. CBF measurements were started after 1 h of infusion of saline or ketanserin. The patients were anaesthetized with thiopentone 5 mg kg-1 followed by isoflurane. During 1 MAC of isoflurane, baseline values were recorded and then CBF autoregulation was examined (mean arterial pressure increased by about 30% with angiotensin). The sequence was repeated with 2 MAC of isoflurane. CBF was measured by the i.v. xenon-133 technique. CMRO2 was calculated as the product of CBF and the cerebral arterio-venous oxygen content difference. Ketanserin had no effect on CBF, CMRO2 or CBF autoregulation during isoflurane anaesthesia, therefore all patients were pooled for evaluation of the effect of isoflurane. Increasing isoflurane anaesthesia from 1 to 2 MAC increased mean CBF from 41 to 49 ml/100 g min-1 (P < 0.01) and decreased mean CMRO2 from 1.5 to 1.1 ml/100 g min-1 (P < 0.001) and thus abolished the coupling between flow and metabolism. The CBF autoregulation test indicated that autoregulation was disrupted at 2 MAC, but not during 1 MAC isoflurane anaesthesia.

Adult↗

Thyroid volume and morphology and urinary iodine excretion in a Danish municipality.

In order to throw light upon the eventual need for iodine supplementation in Denmark, four age groups of women (15, 30, 45 and 60 years) from the Holbaek municipality were invited for a clinical and ultrasound study of thyroid volume, structure and function. Of the 570 women invited, 391 accepted and were divided into the following groups: group I: 15 years, N = 113; group II: 30 years, N = 100; group III: 45 years, N = 98; group IV: 60 years, N = 80. The results were as follows the thyroid gland was palpable in 39% and visible in 16% of the entire group; 19% had a family history of thyroid disorders and 7.6% had a previous thyroid disorder. Thyroid volumes (median (range)) as measured by ultrasound were 12 ml (4-29 ml), 18 ml (5-47 ml), 18 ml (7-64 ml) and 18 ml (9-51 ml) in groups I-IV, respectively. The calculated 24-h iodine excretion was 65 micrograms (19-365 micrograms), 88 micrograms (15-274 micrograms), 97 micrograms (40-737 micrograms) and 83 micrograms (50-999 micrograms) in groups I-IV, respectively. An abnormal echo structure was present in 3, 10, 21 and 30%, respectively. Defining a goitre as a thyroid volume above 28 ml indicated a goitre prevalence of 17% in females aged 30-60 years in the Holbaek area of Denmark. Among the 60-year-old women, 3% had a clinically significant goitre (WHO grade III). Thyroid volume did not correlate with iodine excretion. The benefit of iodine supplementation is discussed.

Adolescent↗

N-acetylcysteine inhibits angiotensin converting enzyme in vivo.

Nitrate tolerance has been explained by 1) a direct loss of pharmacological effect due to reduced bioconversion and 2) an indirect effect due to activation of the renin/angiotensin system and counter-regulatory vasoconstriction. The sulfhydryl compound N-acetylcysteine (NAC) has been shown to attenuate and partly counteract tolerance to nitrates, and this effect has been attributed to a nitrate/sulfhydryl interaction and increased production of vasoactive intermediates. The effect of NAC on counter-regulatory mechanisms is, however, unknown. This study examined whether NAC modulates the function of the renin/angiotensin system in normal rats and in nitrate-tolerant healthy volunteers. Animal study: Conscious rats received NAC (5 mmol/kg/hr i.v., n = 8) or placebo (N-acetylserine, n = 8). Two hours of NAC infusion significantly reduced the pressor effect of angiotensin I (ANG I) by 39 +/- 14% (mean +/- SEM) and reduced angiotensin converting enzyme activity by 31% in plasma (N-acetylserine: 74 +/- 9 nmol/min/mg, NAC: 51 +/- 7) and 43% in kidney (N-acetylserine: 0.9 +/- 0.3, NAC: 0.5 +/- 0.1 nmol/min/mg protein) (P < .05). Clinical study: Isosorbide dinitrate (5 mg/hr) was infused into six male volunteers for 48 hr. NAC (2 g i.v. followed by 5 mg/kg/hr) was co-infused from 24 to 48 hr. Plasma angiotensin II (ANG II) increased during the first 24 hr of isosorbide dinitrate infusion and decreased from 28 +/- 4 to 14 +/- 2 ng/l after 2 hr of NAC infusion (P < .05). The results suggest that sulfhydryl supplementation modifies the function of the renin/angiotensin system in vivo, an effect probably mediated by inhibition of angiotensin converting enzyme activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcysteine↗

Effect of ketanserin on global cerebral blood flow and cerebral oxygen metabolism during midazolam-fentanyl or isoflurane anaesthesia.

We have studied the effect of ketanserin on cerebral blood flow (CBF), cerebral oxygen metabolism (CMRO2) and cerebrovascular carbon dioxide reactivity in 19 adult patients undergoing lumbar disc operation--10 during midazolam-fentanyl anaesthesia (group A) and nine during isoflurane anaesthesia (group B). Measurements were made in each patient whilst awake, during anaesthesia, during anaesthesia with ketanserin and during anaesthesia with ketanserin and hyperventilation. CBF was measured by the i.v. xenon-133 technique. CMRO2 was calculated as the product of CBF and the cerebral arterio-venous oxygen content difference. In the awake state, CBF was 52 and 51 ml/100 g min-1 and CMRO2 3.8 and 3.5 ml/100 g min-1 in groups A and B, respectively. After induction of anaesthesia, CBF decreased 37% in group A and 22% in group B (P < 0.05); CMRO2 decreased 26% in group A and 51% in group B (P < 0.05). Adding ketanserin did not change CBF or CMRO2 in either group. The carbon dioxide reactivity of the cerebral vessels during anaesthesia with ketanserin was 15.4% kPa-1 in group A and 24% kPa-1 in group B. We concluded that ketanserin, in a clinically recommended dose, administered during midazolam-fentanyl or isoflurane anaesthesia had no effect on global CBF, CMRO2 or the relationship between the two factors. Cerebrovascular carbon dioxide reactivity was preserved.

Adult↗

Permanent, skin penetrating, bone-anchored titanium implants. A clinical study of host-reaction in bone and soft tissue.

In 12 patients with a skin penetrating retroauricular titanium-implant (Brånemark) the reaction in bone and soft tissue was studied. Observation time was 6 to 36 months. All implants were "osseointegrated", as assessed by repeated manual test, X-ray examination and 99mTC-scintigraphy. Soft tissue reactions appeared to be slight and clinically insignificant. However, all patients produced crusts around the abutment. When the abutment was removed varying degrees of inflammatory reaction in the skin penetration could be observed in most patients. A theory for the development and cause of the soft tissue reactions is proposed and changes in the operative procedure and the design of the abutment to reduce the host reaction are suggested. It is stressed that the clinical significance of this host reaction is uncertain and above all has to be weighed against the important benefits this implant system offers to a severely handicapped group of patients.

Adult↗

Radioimmunoassay of endothelin in human plasma.

A specific and sensitive radioimmunoassay (RIA) for determination of endothelin-1 (ET-1) in human plasma has been developed. Antibodies were raised in rabbits using synthetic ET-1 conjugated to thyroglobulin as immunogen. The antibodies obtained were used at a final dilution of 1:300,000 yielding maximum binding of 61.7 +/- 3.0% (mean +/- 1 SD, n = 20) of 125I-ET-1. The ID50 (inhibitory dose 50%) was 4.5 +/- 0.6 fmol/100 microliters (mean +/- 1 SD, n = 20). The sensitivity of the RIA was 0.33 fmol/100 microliters standard solution. No cross reactivity was observed with endothelin-3, big-endothelin-1, atrial natriuretic factor, angiotensin I or angiotensin II. The cross-reactivity with endothelin-2 was 100%. Endothelin was extracted from acidified plasma with Sep-pak C18 cartridges and recovery of ET-1 added to normal plasma was 70.9 +/- 10.3% (mean +/- 1 SD, n = 12). The concentration of ET-1 in plasma from normal subjects was 1.5 +/- 0.4 pmol/l (mean +/- 1 SD, n = 11) ranging from 1.0 to 2.2 pmol/1. Extracts of normal human plasma subjected to high performance liquid chromatography on a reverse phase C18 column showed one peak of immunoreactivity co-eluting with the standard for ET-1. From these data it is concluded that the immunoreactive material measured in normal plasma with the present RIA is identical to ET-1.

Animals↗

Gastric emptying of liquid meals: validation of the gamma camera technique.

In order to assess the extent of errors and to provide correction factors for gamma camera gastric emptying studies of liquid meals labelled with radionuclides (99Tcm or 113Inm), a series of phantom studies were performed with different gastric emptying procedures, gamma cameras and data handling systems. To validate the overall accuracy of the method, 24 combined aspiration and gamma camera gastric emptying studies were carried out in three normal volunteers. Gastric meal volume, expressed as a percentage of the original volume of the meal ingested was underestimated due to scattered radiation from the stomach. The underestimation was 7-20% varying with the size of the gastric region of interest (ROI), the energy of the nuclide and the fraction of meal in the stomach. The overestimation, due to scattered radiation from the gut, was negligible (1-3%) for any of the procedures with 10% of the meal situated outside the stomach at a distance of at least 1 cm. Sections of the duodenal loop were always inside the stomach ROI and were likely to contain a constant fraction of the meal (3-10%). The gamma camera technique eliminated much of the error due to variations of stomach geometry and produced accurate quantitative gastric emptying data comparable to those obtained by evacuation (P greater than 0.10), when the entire field maximum 1-min count achieved within the first 20 min of a study was taken as representing the original volume of the meal ingested, and when corrections for area related errors due to scattered radiation from the stomach were performed.

Gastric Emptying↗

Evaluation of renal function and morphology in children by 99mTc-DTPA gamma camera renography.

The purpose of the present investigation was to evaluate the use of 99mTc-DTPA (diethylenetriaminepenta-acetate) gamma camera renography for the study of kidney function as well as morphology. Sixty-nine children with urinary tract infection or congenital hydronephrosis aged 6 days to 13.6 years were studied. A method for determination of the glomerular filtration rate (GFR) from the recorded curves without use of blood or urine samples was tested in 65 consecutive children. From each renogram an uptake index was determined. After a weight/height correction the sum of right and left kidney uptake index correlated with total GFR determined from plasma clearance of 51Cr-EDTA (ethylenediaminetetra-acetate) measured on the same day (r = 0.96). The relative standard error of estimating GFR from the renograms was 10.7% at GFR = 100 ml/min and 14.6% at GFR = 50 ml/min. In a subgroup including 20 children no difference was found in kidney morphology and length studied by renography and intravenous urography, the latter providing more details concerning the urinary tract. Relative kidney length did not correlate with relative renal function determined by renography, emphasizing the difficulty in determination of relative renal function by urography. In conclusion, not only relative but also absolute renal function (GFR) can be determined in children by 99mTc-DTPA renography; at the same time kidney and urinary tract morphology are evaluated. In our hands, 99mTc-DTPA renography has become a useful diagnostic tool, lowering the need for the more cumbersome intravenous urography and 51Cr-EDTA plasma clearance. However, intravenous urography is mandatory for the detailed study of the urinary tract, and use of the 51Cr-EDTA plasma clearance technique is necessary when a very reliable determination of GFR is wanted.

Adolescent↗