PubMed Health⌕ Search

Biomedical subjects

J Møller

Publications and source records attributed to J Møller.

At least 55 records · Page 3Linked to original sources
PubMed1997

The immunodeficiency after allogeneic bone marrow transplantation in man: role of cytokines.

The effect of various cytokines including rIL-1, rIL-2, rIL-3, rIL-4, rIL-6, and growth factors including rNGF, rILGF and rEPGF on the post transplant immunodeficiency after allogeneic bone marrow transplantation was explored in 8 patients. The results show that neither cytokine alone was able to increase the proliferative capability in post transplant lymphocytes, however, when added in conjunction a significant increase in PHA driven proliferation was noted. Any significant lack of growth factors is probably not the only cause of immunodeficiency post transplant, since addition of any of these compounds did not have any influence on the lymphocyte proliferation, and so the data presented here suggest that therapeutic application of any of the investigated cytokines or growth factors to such patients is unlikely to be successful in overcoming the defects of T cell function post grafting.

Acquired Immunodeficiency Syndrome↗
PubMed1996

GLP-1 does not not acutely affect insulin sensitivity in healthy man.

Previous studies have suggested that glucagon-like peptide-1 (GLP-1) (7-36 amide) may have the direct effect of increasing insulin sensitivity in healthy man. To evaluate this hypothesis we infused GLP-1 in seven lean healthy men during a hyper insulinaemic (0.8 mU.kg-1.min-1), euglycaemic (5 mmol/l) clamp. Somatostatin (450 micrograms/h was infused to suppress endogenous insulin secretion, and growth hormone (3 ng.kg-1.min-1) and glucagon (0.8 ng.kg-1.min-1) were infused to maintain basal levels. GLP-1 (50 pmol.kg-1.h-1) or 154 mmol/l NaCl (placebo) was infused after 3 h of equilibration, i.e. from 180-360 min. GLP-1 infusion resulted in GLP-1 levels of approximately 40 pmol/l. Plasma glucose, insulin, growth hormone, and glucagon levels were similar throughout the clamps. The rate of glucose infusion required to maintain euglycaemia was similar with or without GLP-1 infusion (7.69 +/- 1.17 vs 7.76 +/- 0.95 mg kg-1.min-1 at 150-180 min and 8.56 +/- 1.13 vs 8.55 +/- 0.68 mg.kg-1.min-1 at 330-360 min) and there was no difference in isotopically determined hepatic glucose production rates (-0.30 +/- 0.23 vs -0.16 +/- 0.22 mg.kg-1.min-1 at 330-360 min). Furthermore, arteriovenous glucose differences across the forearm were similar with or without GLP-1 infusion (1.43 +/- 0.23 vs 1.8 +/- 0.29 mmol/l), (ANOVA; p > 0.60, in all instances). In conclusion, GLP-1 (7-36 amide) administered for 3 h, leading to circulating levels within the physiological range, does not affect insulin sensitivity in healthy man.

3-Hydroxybutyric Acid↗
PubMed1996

Bioavailability and bioactivity of intravenous vs subcutaneous infusion of growth hormone in GH-deficient patients.

OBJECTIVE: The bioavailability of GH immunoreactive serum concentrations is reduced following subcutaneous (s.c.) as compared with intravenous (i.v.) administration. Whether this difference also translates into a different biological activity remains to be investigated. The aim of the present study was to evaluate the short-term metabolic effects of GH following i.v. and s.c. delivery. DESIGN AND MEASUREMENTS: In a cross-over design 10 GH-deficient patients were randomized to receive GH (0.03 microgram (0.1 mU/kg/min) as a continuous i.v. or s.c. infusion for 39 hours on two different occasions. Preceding each study GH therapy was discontinued for 5 days. Serum profiles of GH, IGF-I, IGF-II, IGF binding protein 3 (IGFBP-3), insulin, glucose and non-esterified fatty acids (NEFA) were recorded during the studies. Serum GH was measured by a polyclonal radio-immunoassay (RIA) and by a double monoclonal immunofluorimetric assay (DELFIA). RESULTS: Higher mean integrated values (AUC) of serum GH (mU/l) were obtained with i.v. GH delivery [47.4 +/- 5.1 (i.v.), 33.3 +/- 3.0 (s.c.), P < 0.05]. The two GH assays showed qualitatively similar results, but higher mean GH concentrations were measured by RIA following both s.c. (P < 0.001) and i.v. infusion (P < 0.001). Serum IGF-I levels displayed different patterns following i.v. and s.c. GH infusion (P < 0.05 by ANOVA) and mean IGF-I levels (micrograms/l) were lower following s.c. GH infusion [159.5 +/- 21.8 (s.c.), 185.2 +/- 27.7 (i.v.), P = 0.002]. Serum IGF-II levels were unaffected by short-term GH treatment and by the route of GH administration. Serum IGFBP-3 levels increased in response to GH administration (P < 0.001), irrespective of route (P = 0.76). The IGF-I/IGFBP-3 molar ratio increased significantly following GH administration (P < 0.001), and a higher ratio was obtained following i.v. infusion (P < 0.005). Subcutaneous GH infusion resulted in significantly lower mean levels of serum NEFA (P < 0.02), whereas similar mean levels of serum insulin (P = 0.54), blood glucose (P = 0.24), energy expenditure (P = 0.13), and respiratory exchange ratio (P = 0.09) were observed on the two occasions. CONCLUSIONS: A reduced bioavailability of s.c. as compared with i.v. administered GH has been recorded with two independent GH assays, and this was also accompanied by a significant, albeit modest, reduction in biological activity.

Adult↗
PubMed1996

Decreased plasma and extracellular volume in growth hormone deficient adults and the acute and prolonged effects of GH administration: a controlled experimental study.

OBJECTIVE: There are few data on the endocrine mechanisms underlying the body fluid changes in GH deficiency and their subsequent alteration following GH replacement. We have therefore investigated the time effects of GH on body fluid distribution and fluid regulating hormones in GH deficient adults. DESIGN: The patients underwent in random order four study periods: (1) saline, a 42-hour infusion following 3 weeks without GH, (2) acute GH, a 42-hour GH infusion following 3 weeks without GH, (3) 3 days GH, a 42-hour GH infusion preceded by 3 weeks without GH and 3 days pretreatment with subcutaneous GH injections, (4) 3 weeks GH, a 42-hour GH infusion after at least 3 weeks GH therapy. SUBJECTS: Seven GH deficient adult males and 8 healthy control subjects. MEASUREMENTS: During each infusion period 24-hour blood pressure was recorded, bioimpedance was repeatedly measured and blood samples were obtained every 6 hours. After 41 hours extracellular and plasma volumes were determined isotopically. Extracellular volume, plasma volume and bioimpedance were measured in the control group. RESULTS: GH increased extracellular volume (saline 16.45 +/- 0.79 vs acute GH 16.83 +/- 0.87; vs 3 days GH 17.58 +/- 0.71; vs 3 weeks GH 17.92 +/- 0.88 l, P = 0.01). After 3 weeks of GH, extracellular volumes in the patients and in the control group were identical (control 17.94 +/- 0.32). Plasma volume was increased only after 3 weeks GH treatment (saline 2.93 +/- 0.16 vs acute GH 3.04 +/- 0.22; vs 3 days GH 3.06 +/- 0.07; vs 3 weeks GH 3.37 +/- 0.18 l, P = 0.03), and was decreased compared to the control group (control 3.56 +/- 0.03 l, P < 0.01). Bioimpedance decreased significantly in all treatment periods and was significantly increased compared to the control group. Plasma renin increased during GH administration (saline 16.2 +/- 1.9 vs acute 19.0 +/- 1.9; vs 3 days GH 30.8 +/- 3.0; vs 3 weeks GH 27.0 +/- 3.0 mU/l, P = 0.03), whereas aldosterone and atrial natriuretic factor (ANF) levels remained unaffected by GH. GH caused an increase in systolic blood pressure (BP) and heart rate, whereas diastolic BP remained unaffected. CONCLUSIONS: The present data show that GH deficiency is associated with decreased plasma volume and extracellular volume. GH exposure acutely increases extracellular volume, whereas substitution for a longer time was required to normalize both extracellular and plasma volumes. Renin seems to be involved in these fluid volume regulating effects of GH.

Adult↗
PubMed1996

Sarcoidosis causes abnormal seasonal variation in 1,25-dihydroxy-cholecalciferol.

OBJECTIVES: The spontaneous seasonal variations in the calcium regulating hormones 1,25-dihydroxy-cholecalciferol (1,25-DHCC) and parathyroid hormone (PTH) were investigated in patients with sarcoidosis. DESIGN: Controlled, prospective observational study with measurements in the winter and summer seasons, respectively. SUBJECTS: Twelve patients (age: median 33, range 21-54 years) with biopsy-verified (n = 8) sarcoidosis were included as well as 11 age-matched healthy control subjects. MAIN OUTCOME MEASURES: Serum values of calcium, ionized calcium, phosphate, chloride, bicarbonate, creatinine, albumin, angiotensin-converting enzyme, alkaline phosphatase, 1,25-DHCC, and PTH. Also, 24-h whole body retention of 99mTc methylene-diphosphonate was assessed. RESULTS: The patient group showed an increased level of 1,25-DHCC in the summer season (w:146 +/- 67, s:198 +/- 73 pmol L-1; P < 0.01) in contrast to the opposite finding among controls (w:161 +/- 34, s:144 +/- 43 pmol L-1; P < 0.05). Comparing the individual seasonal changes between the two groups, the difference was marked (P < 0.001). Compared with controls, total serum calcium was elevated in the summer season in the patient group (P < 0.05), in which the same parameter correlated positively with 1,25-DHCC (r = 0.658; P < 0.01). PTH was increased two to three times above the control values throughout the year (patients: w:0.37 +/- 0.13, s:0.24 +/- 0.08 micrograms L-1; controls: w:0.14 +/- 0.09, s:0.10 +/- 0.04 micrograms L-1; P < 0.001); although, the level of this hormone was still found within the reference interval. 24-h whole body bone scintigraphy failed to show any seasonal variation in bone metabolism. In contrast, serum alkaline phosphatase was found to be increased during the summer season compared with the control group (P < 0.001). Angiotensin-converting enzyme showed no seasonal variation. CONCLUSIONS: In sarcoidosis, 1,25-DHCC is abnormally regulated throughout the year, with a significantly higher serum level in the summer season. Uncontrolled production of 1,25-DHCC in sarcoid pulmonary alveolary macrophages is possibly responsible for hypercalcaemic episodes, and this parameter should be used as a marker of disease activity.

Adult↗
PubMed1996

Dose-dependent effects of recombinant human growth hormone on biochemical markers of bone and collagen metabolism in adult growth hormone deficiency.

Administration of growth hormone (GH) to patients with growth hormone deficiency (GHD) has beneficial effects, but so far has been employed only empirically. We have, therefore, investigated the dose-dependent effect of GH on target tissue by studying biochemical markers of bone and collagen turnover in GHD. Then patients with GHD (nine males and one female aged 21-43 years, mean age 28 years) participated in the study. Growth hormone deficiency was defined as a peak serum GH response of less than 15 mU/l in two provocation tests. After a 4-week run-in period, the study population received increasing doses of GH at 4-week intervals (1, 2 and 4 U/m2). Blood samples were collected in the fasting state at 7.00 h on the last day of each period and assayed for serum levels of osteocalcin (S-BGP), bone alkaline phosphatase (B-ALP), C-terminal propeptide of type I collagen (S-PICP), carboxy-terminal pyridinoline cross-linked telopeptide of type I collagen (S-ICTP) and N-terminal propeptide of type III collagen (S-PIIINP). Following replacement therapy, serum insulin-like growth factor I and insulin-like growth factor binding protein 3 increased sequentially with time (p < 0.001 and p < 0.001, MANOVA) and the values were elevated significantly over baseline levels after treatment with 1 U/m2. Serum BGP values were below normal at the start of the study and increased gradually following GH treatment to levels in the low-normal range. Baseline values for serum bone alkaline phosphatase (B-ALP), PICP and PIIINP were within the normal range. The collagen parameters increased with GH replacement (p < 0.001, MANOVA) to levels above normal, whereas B-ALP stayed within normal limits. Serum ICTP values were elevated above the normal range at baseline, indicating increased bone resorption in GHD. A linear increase in values was observed with GH treatment (p < 0.001, MANOVA). Serum ICTP did not correlate significantly with the bone formative parameters but was correlated positively to PIIINP. The sensitivity of S-ICTP as a bone resorptive marker is thus questioned. In conclusion, a dose-dependent increase in markers of growth hormone metabolism and in biochemical markers of both bone and non-bone collagen synthesis was seen following incremental doses of GH in GHD.

Adult↗
PubMed1996

Free and total insulin-like growth factors and insulin-like growth factor binding proteins during 14 days of growth hormone administration in healthy adults.

The objective was to investigate the effect of growth hormone (GH) administration on circulating levels of free insulin-like growth factors (IGFs) in healthy adults. Eight healthy male subjects were given placebo and two doses of GH (3 and 6 IU/m2 per day) for 14 days in a double-blind crossover study. Fasting blood samples were obtained every second day. Free IGF-I and IGF-II were determined by ultrafiltration of serum. Total IGF-I and IGF-II were measured after acid-ethanol extraction. In addition, GH, insulin, IGF binding protein 1 (IGFBP-1) and IGFBP-3 were measured. Serum-free and total IGF-I increased in a dose-dependent manner during the 14 days of GH administration. After 14 days, serum-free IGF-I values were 610 +/- 100 ng/l (mean +/- SEM) (placebo), 2760 +/- 190 ng/l (3 IU/ m2) and 3720 +/- 240 ng/l (6 IU/m2) (p = 0.0001 for 3 and 6 IU/m2 vs placebo; p = 0.004 for 3 IU/m2 vs 6 IU/m2). Total IGF-I values were 190 +/- 10 micrograms/l (placebo), 525 +/- 10 (3 IU/m2), and 655 +/- 40 micrograms/l (6 IU/m2) (p < 0.0001 for 3 and 6 IU/m2 vs placebo; p = 0.04 for 3 IU/m2). There were no differences in the levels of free or total IGF-II during the three study periods. Insulin-like growth factor binding protein 1 was decreased during GH administration (p = 0.04 for placebo vs 3 IU/m2; p = 0.006 for placebo vs 6 IU/m2). In conclusion, fasting serum free IGF-I increased dose dependently during GH administration and free IGF-I increased relatively more than total IGF-I. This may partly be due to the decrease in IGFBP-1.

Adult↗
PubMed1996

Calibration of the Ektachem Amylase method using human reference materials and the Phadebas Blue Starch method as an interim reference method.

In a multilaboratory study a consensus was established to calibrate the Ektachem Amylase method to reproduce the results of the Phadebas Blue Starch method. The calibration graph has a slope = 3.39 and intercept = 25. For the Ektachem Amylase method the reaction-rate ratio between salivary and pancreatic amylase was calculated to be 0.89, relative to that of the Phadebas Blue Starch method. A calibration value for the Nordic Amylase Calibrator to be used on Ektachem analysers was determined to be close to 469 U l-1 for the current batch. However, since the difference from the stated value of 460 U l-1 is negligible, the authors recommend the use of the stated value for this and future batches of the Nordic Amylase Calibrator. An error of around 10% introduced by the presence of salivary amylase is comparable to the methods accepted by the Scandinavian Committee on Enzymes. Introduction of a consensus calibration reduced the interlaboratory variation by up to 40% at all levels.

Amylases↗
PubMed1996

Age- and gender-specific reference intervals for total homocysteine and methylmalonic acid in plasma before and after vitamin supplementation.

We present reference intervals for total homocysteine and methylmalonic acid in plasma based on samples from 126 women (ages 20-85 years, median 49 years) and 109 men (ages 20-84 years, median 50 years). The central 0.95 interval for methylmalonic acid was 0.08-0.28 micromol/L. Supplementation with cyanocobalamin caused a nonsignificant decrease in methylmalonic acid. Supplementation with folic acid caused a decrease in homocysteine concentrations, with data analysis identifying two significantly different clusters: 182 subjects with the lowest initial concentrations (7.76 +/- 1.54 micromol/L, mean +/- SD) and the smallest decrease (1.26 +/- 0.96 micromol/L), and 53 subjects with the highest initial concentrations (12.33 +/- 2.04 micromol/L) and greatest decrease (4.14 +/- 1.32 micromol/L). We argue in favor of the age- and gender-specific central 0.95 intervals obtained for the 182 subjects before being supplemented with folic acid: 4.6-8.1 micromol/L for subjects at <30 years; 4.5-7.9 micromol/L for women, ages 30-59 years; 6.3-11.2 micromol/L for men, ages 30-59 years; and 5.8-11.9 micromol/L for subjects at >60 years.

Adult↗
PubMed1996

Immunodeficiency after allogeneic bone marrow transplantation in man: the role of antigen presenting cells.

We investigated the proliferative response of donor T cells to phytohemagglutinin (PHA) presented by donor non-T cells in 7 patients after allogeneic bone marrow transplantation. Compared with the cellular response in the healthy marrow donors, T cell proliferation was found to be deficient in every recipient, from 130 to 739 days after grafting. Results of cell mixing experiments showed that the non-T cells of the patients were as capable as healthy donor non-T cells in presenting PHA to normal donor T cells. However, T cells from patients did not proliferate after substituting donor non-T cells for non-T cells from patients. This inability of T cells to proliferate was most likely the result of ineffective interactions among T cell subsets in patients after allogeneic bone marrow transplantation.

Adolescent↗
PubMed1996

Cytotoxic T cell activity after HLA-mismatch bone marrow transplantation.

Six patients with various hematologic diseases were treated with HLA-haploidentical bone marrow mismatched for 1-2 loci at the disparate chromosome with a relative response in the mixed lymphocyte reaction (MLR) ranging between 0.04 and 0.96 (median 0.27). Thirty to 371 days after bone marrow grafting, patient lymphocytes (of donor origin) were tested for reactivity in mixed lymphocyte culture (MLC) and cell mediated lympholysis (CMLy) to lymphocytes from the host (cryopreserved before grafting), the marrow donor, and unrelated individuals. After grafting, Lymphocytes from the patients showed a host-specific decrease in proliferation and in cytotoxic response (%51Cr release in a standard chromium release assay), when compared to the pretransplant host-specific donor response, whereas the responses towards third party cells were unaffected. This host-specific unresponsiveness after HLA-mismatch bone marrow transplantation is compatible with a clonal deletion theory and might be the reason that this procedure is at all possible.

Adolescent↗
PubMed1995

Metabolic effects of growth hormone in humans.

Growth hormone (GH) has acute actions to stimulate lipolysis and ketogenesis after 2 to 3 hours, effects that may be important in the adaptation to stress and fasting. This is accompanied by a decrease in insulin sensitivity in both liver and muscle. These combined effects may be very deleterious to insulin-dependent diabetic patients, in whom increased GH secretion may precipitate and maintain acute metabolic derangement (ketoacidosis) and be a major initiator of the dawn phenomenon. On the other hand, augmented GH secretion plays a beneficial role in the defense against hypoglycemia, in particular during prolonged hypoglycemia and in patients with impaired ability to secrete other counterregulatory hormones appropriately. It is also certain that GH is a potent anabolic hormone in terms of promoted nitrogen retention, but the extent to which these well-known actions are direct or secondary to hyperinsulinemia, increased activity of insulin-like growth factors (IGFs), or release of protein-conserving lipid intermediates has eluded precise characterization.

Carbohydrate Metabolism↗
PubMed1995

Fuel metabolism in growth hormone-deficient adults.

Apart from being a stimulator of longitudinal growth, growth hormone (GH) regulates fuel metabolism in children and adults. A halfmark is mobilization of lipids, which involves an inhibition of lipoprotein lipase activity in adipose tissue and activation of the hormone sensitive lipase. Suppression of basal glucose oxidation and resistance to insulin are other important effects. This may cause concern during GH substitution in GH-deficient adults, some of whom may present with insulin resistance due to concomitant abdominal obesity. However, there are data to suggest that the GH-induced reduction in fat mass and increase in lean body mass may offset the insulin antagonistic actions of the hormone. The nitrogen-retaining effects of GH seem to involve a direct stimulation of protein synthesis in addition to secondary effects such as generation of insulin-like growth factor-I (IGF-I), hyperinsulinemia, and promotion of lipolysis. Thus, during periods of substrate affluence, GH acts in concert with insulin and IGF-I to promote protein anabolism. Postabsorptively, GH is primarily lipolytic and thereby indirectly protein-sparing. This effect becomes further accentuated with more prolonged fasting. In that sense, GH is unique by its preservation of protein during both feast and famine. These fuel metabolic effects add merit to the principle of GH substitution in hypopituitary adults.

Adult↗
PubMed1995

Somatostatin enhances insulin-stimulated glucose uptake in the perfused human forearm.

Somatostatin is widely used in experimental metabolic studies to control hormone actions. It has also been suggested that, in addition to its well known suppressive effects, somatostatin per se may increase insulin sensitivity. In order to examine this suggestion, we gave six healthy male volunteers (age 33 +/- 1 yr, mean +/- SEM; body mass index, 24.1 +/- 0.6 kg/m2) either a local intraarterial (brachial artery) or a systemic venous infusion of 25 micrograms/h somatostatin twice. The study consisted of a 1-h basal period and a 2-h systemic hyperinsulinemic (0.4 mU/kg.min) euglycemic clamp. Compared with the systemic control infusion, local forearm perfusion with somatostatin caused a 55% increase in insulin-stimulated forearm glucose uptake (0.74 +/- 0.18 vs. 0.47 +/- 0.19 mmol/L, P < 0.05). Intraarterial somatostatin perfusion did not alter basal forearm glucose uptake (0.14 +/- 0.07 vs. 0.17 +/- 0.12 mmol/L), the amount of glucose administered during the clamp (M-value, 3.2 +/- 0.5 vs. 3.0 +/- 0.6 mg/kg.min), or the levels of insulin, C-peptide, glucagon, or GH. Intermediary metabolite exchange across the forearm, total forearm blood flow, and oxygen saturations also remained stable. Glucose concentrations were slightly higher (0.06 +/- 0.01 mmol/L) in arterial than in arterialized blood, whereas lactate concentrations were comparatively decreased (108 +/- 51 mumol/L) in arterial blood. Our data suggest that somatostatin increases insulin-stimulated muscle utilization of glucose through local mechanisms. Although the nature of this increase remains to be established, it should be taken into consideration in metabolic studies using somatostatin.

3-Hydroxybutyric Acid↗
PubMed1994

Insulin-like growth factors (IGF)-I and -II and IGF binding protein-1, -2, and -3 in patients with acromegaly before and after adenomectomy.

The interrelationship between insulin-like growth factors (IGFs) and their major binding proteins (IGFBPs) as a function of disease activity in acromegaly has not previously been prospectively evaluated. We studied basal and insulin-stimulated serum levels of IGF-I and -II and IGFBP-1, -2, and -3 in six acromegalic patients before and 2 months after successful adenomectomy compared with a group of sex- and age-matched healthy, untreated subjects. All were studied postabsorptively (11 AM) and at the end of a 2-hour euglycemic glucose clamp (0.4 mU insulin/kg x min). Serum IGF-I levels (mean +/- SE) were elevated in acromegaly but were normalized following therapy (basal state IGF-I [micrograms/L], 857 +/- 119 [active] v 255 +/- 65 [postoperative] v 190 +/- 20 [control]). Serum IGF-II levels did not change following therapy and were similar to those of the control group. IGF levels did not change during the clamp. Serum IGFBP-3 levels were elevated in active acromegaly, but were normalized after therapy (basal state IGFBP-3 [micrograms/L] 6,983 +/- 612 [active] v 3,939 +/- 504 [postop] v 3,358 +/- 125 [control]). The molar ratio of (IGF-I+IGF-II): IGFBP-3 was similar in all studies. Serum IGFBP-1 interacted significantly with time in all studies, exhibiting a gradual decrease in the basal state and ensued by further suppression during the clamp. Insulin and IGFBP-1 correlated inversely in the pooled data and in the acromegalic patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Acromegaly↗