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Biomedical subjects

K Rasmussen

Publications and source records attributed to K Rasmussen.

At least 127 records · Page 7Linked to original sources
PubMed1996

Pancreatic endocrine function in recipients of segmental and whole pancreas transplantation.

To determine potential abnormalities in beta-cell function after pancreas transplantation, the secretory capacity of the pancreatic grafts was assessed by measuring the glucose-potentiating effect on arginine-induced insulin secretion in recipients of cadaveric segmental (SPx; n = 8) and whole organ pancreas grafts (WPx; n = 6) and compared to that in nondiabetic kidney transplant recipients (Kx; n = 6) and normal controls (Ns; n = 7). alpha-Cell adaptation to increasing hyperglycemia and the glucagon response to arginine stimulation were also studied. The secretory capacity of the beta-cell to arginine-induced (5 g L-arginine) insulin secretion was measured at fasting plasma glucose and 15 and 30 mmol/L glucose. Insulin secretion was evaluated by the calculation of insulin secretion rates. Insulin sensitivity was markedly reduced in all three transplanted groups compared to that in normal subjects (P < 0.05). The prestimulation insulin secretion rate and maximal insulin secretion rate in response to hyperglycemia and arginine were significantly lower in SPx than in WPx, Kx, or Ns (P < 0.05). The incremental amount of insulin secreted in response to arginine was reduced by 40-70% in SPx depending on glycemia compared to that in all other groups (P < 0.05), among which there were no statistical differences. Both SPx and WPx demonstrated suppression of glucagon release in response to graded hyperglycemia, but failure to adequately suppress arginine-induced glucagon release. In conclusion, recipients of cadaveric segmental pancreas grafts display a markedly reduced maximal insulin secretory reserve capacity. This impairment was primarily due to an insufficient beta-cell mass. Taking the concomitant insulin resistance into account, recipients of a cadaver whole organ pancreas graft had an impaired insulin secretory reserve capacity as well.

Adult↗
PubMed1996

Accuracy of routine echocardiographic measurements made by an inexperienced examiner through tele-instruction.

The reproducibility and accuracy of routine echocardiographic measurements made by an inexperienced doctor using tele-instruction were evaluated. Thirty-eight patients were first examined at a local hospital by an inexperienced doctor instructed by a specialist 450 km away at a university hospital. The specialist then examined the patients at the local hospital using the same equipment, after an average of 50 days. The accuracy of M-mode and quantitative Doppler measurements was comparable to that observed in reproducibility studies made under normal examination conditions. There were no systematic measurement errors. No important M-mode information was missed except evidence of left ventricular hypertrophy in six patients. In the two-dimensional examination there were differences of clinical significance in only three patients. There were no clinically important differences in the Doppler quantification of mitral and aortic regurgitation. Tele-instructed echocardiography is also an excellent educational tool, allowing an inexperienced examiner gradually to take responsibility for the local echocardiographic service.

Adult↗
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↗
PubMed1995

Nicotine withdrawal leads to increased firing rates of midbrain dopamine neurons.

In order to explore the neurophysiology of nicotine withdrawal, we examined the activity of substantia nigra (A9) and ventral tegmental area (A10) dopamine cells in rats undergoing withdrawal from chronic exposure to nicotine. Animals were exposed to nicotine (6 mg kg-1 day-1 base) via s.c. implanted osmotic minipumps. After 12 days the pumps were removed and the animals allowed to go through spontaneous withdrawal. Rats were anesthetized on various days of the procedure and single-unit recordings were made from A9 and A10 dopamine cells. Chronic administration of nicotine led to a decreased firing rate of A10, but not A9, dopamine cells. Upon withdrawal from the chronic exposure to nicotine, the firing rates of A10 dopamine cells returned to control levels, while the firing rate of A9 dopamine cells significantly increased above control levels. This increased dopamine neuronal activity may play a role in some behavioural symptoms of nicotine withdrawal.

Acoustic Stimulation↗
PubMed1995

Identification of a novel TGF-beta-regulated gene encoding a putative zinc finger protein in human osteoblasts.

The TGF-beta family of growth factors has been extensively studied and found to play major roles in bone physiology and disease. A novel, TGF-beta-inducible early gene (TIEG) in normal human fetal osteoblasts (hFOB) has been identified using differential-display PCR. Using this differentially expressed cDNA fragment of TIEG to screen a hOB cDNA library, a near full-length cDNA for this gene was isolated. Northern analyses indicated that the steady-state levels of the 3.5 kb TIEG mRNA increased within 30 min of TGF-beta treatment of human osteoblasts and reached a maximum of 10-fold above control levels at 120 min post-treatment. This regulation was independent of new protein synthesis. Computer sequence analyses indicates that TIEG mRNA encodes for a 480 amino-acid protein. The TIEG protein contains three zinc finger motifs, several proline-rich src homology-3 (SH3) binding domains at the C-terminal end, and is homologous in this region to the zinc finger-containing transcription factor family of genes. A growth factor/cytokine-specific induction of TIEG has been shown. TIEG expression in hFOB cells was highly induced by TGF-beta and bone morphogenetic protein-2 (BMP-2), with a moderate induction by epidermal growth factor (EGF), but no induction by other growth factors/cytokines was observed. In addition to osteoblastic cells, high levels of TIEG expression were detected in skeletal muscle tissue, while low or no detectable levels were found in brain, lung, liver or kidney. Because TIEG is an early induced putative transcription factor gene, and shows a growth factor induction and tissue specificity, its protein product might play an important role as a signalling molecule in osteoblastic cells.

Base Sequence↗
PubMed1995

[Renal function during treatment with angiotensin converting enzyme inhibitors].

The use of ACE-inhibitors has increased greatly during the last years. They were first used in treating hypertension, but nowadays cardiac diseases, mainly cardiac failure, are common indications. This means that the drugs are used in the treatment of more elderly patients who often have generalised atherosclerosis. This means that the patients must be controlled more often after initiation of treatment, especially concerning kidney function, since treatment with ACE-inhibitors can cause pronounced changes in renal haemodynamics and kidney function. This review focuses on the effects of ACE-inhibitors on renal haemodynamics and kidney function, which may be positive, with preservation of kidney function in diabetic and other chronic nephropathy, or negative, for example in cases with atherosclerotic stenosis of large or small renal arteries. It is concluded, that in cases of diabetic nephropathy an ACE-inhibitor is the "drug of choice" for treatment of hypertension. Furthermore the ACE-inhibitors seem to reduce the rate of deterioration of renal function and proteinuria in other kidney diseases. It is emphasized, that during treatment with ACE-inhibitors kidney function must be controlled before and following one to two weeks of treatment, if the dose is changed and in all cases following two to three months of treatment. Special attention should be given to patients with atherosclerotic manifestations e.g. angina.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1995

[Renal function during treatment of chronic renal failure with angiotensin converting enzyme inhibitors].

The effect on kidney function fo treatment of cardiac failure with ACE-inhibitors was examined retrospectively in a material of 87 consecutive patients. Furthermore, it was evaluated whether concomitant treatment with diuretics or existing generalised atherosclerosis as indicated by ongoing treatment with nitrates could be a risk factor concerning reduction of kidney function. In 11.9% of the patients an increase in S-creatinine of > 30% was observed during the first weeks of treatment. It was only necessary to stop treatment in two of these patients. In the remainder S-creatinine decreased again during ongoing treatment. In another 10.7% of patients an increase of 20-30% in S-creatinine was observed. Seventy-two point six percent of the patients had unchanged kidney function during treatment with an ACE-inhibitor. Ongoing treatment with diuretics did not seem to be a risk factor for developing reduced kidney function, whereas significantly more patients on treatment with nitrates, indicating generalised atherosclerosis, developed reduced kidney function during treatment with ACE-inhibitors. It is recommended to control kidney function before, one to two weeks and two to three months following initiation of treatment with ACE-inhibitors and to pay special attention to patients with generalised atherosclerosis.

Adult↗
PubMed1995

TGF-beta regulation of nuclear proto-oncogenes and TGF-beta gene expression in normal human osteoblast-like cells.

Transforming growth factor-beta (TGF-beta) is present in high levels in bone and plays an important role in osteoblast growth and differentiation. In order to dissect the molecular mechanisms of action of TGF-beta on osteoblasts, the effects of TGF-beta on the steady state mRNA levels of c-fos, c-jun, and jun-B proto-oncogenes on normal human osteoblast-like cells (hOB) and a transformed human osteoblast cell line (MG-63) were measured. Treatment of hOBs with 2 ng/ml of TGF-beta 1 resulted in a rapid increase in c-fos mRNA levels as early as 15 min post-treatment. A maximum (10-fold) increase was observed at 30 min after TGF-beta treatment followed by a decrease to control values. Similar responses were measured whether the cells were rapidly proliferating or quiescent. TGF-beta 1 induced jun-B mRNA levels more gradually with steady increase initially observed at 30 min and a maximum induction measured at 2 h post-TGF-beta treatment. In contrast, TGF-beta treatment caused a time dependent decrease in the c-jun mRNA levels, an opposite pattern to that of jun-B mRNA. Treatment of hOBs with TGF-beta 1 in the presence of actinomycin-D abolished TGF-beta 1 induction of c-fos mRNA, suggesting that TGF-beta action is mediated via transcription. In the presence of cycloheximide, TGF-beta causes super-induction of c-fos mRNA at 30 min, indicating that the c-fos expression by TGF-beta is independent of new protein synthesis. Further, transfection of 3 kb upstream region of jun-B promoter linked to a CAT reporter gene into ROS 17/2.8 cells was sufficient to be regulated by TGF-beta 1. Interestingly, TGF-beta treatment also increased the mRNA levels of TGF-beta 1 itself at 4 h post TGF-beta treatment, with a maximum increase observed at 14 h of treatment. TGF-beta 1 treatment for 30 min were sufficient to cause a delayed increase in TGF-beta protein secretion within 24 h. These data support that TGF-beta has major effects on hOB cell proto-oncogene expression and that the nuclear proto-oncogenes respond as rapid, early genes in a cascade model of hormone action.

Animals↗
PubMed1995

NMDA antagonists and clonidine block c-fos expression during morphine withdrawal.

The c-fos gene is expressed in the central nervous system (CNS) in response to neuronal stimuli. Induction of c-fos in certain CNS regions occurs following naltrexone precipitated withdrawal in morphine dependent rats. Non-competitive (MK801) and competitive (LY274614) NMDA receptor antagonists and clonidine, an alpha2 partial agonist, attenuate the intensity of naltrexone precipitated withdrawal. We determined the levels of c-fos mRNA by solution hybridization in several brain regions in control and morphine dependent rats following pretreatment with saline, MK801 (1 mg/kg, s.c.), LY274614 (100 mg/kg, i.p.), or clonidine (1.5 mg/kg, i.p.). Morphine treatment increased c-fos mRNA levels in striatum (STR) and amygdala (AMY). Naltrexone did not alter c-fos mRNA levels in placebo-treated rats. However, naltrexone increased c-fos mRNA levels in morphine dependent rats in the nucleus accumbens (NA), frontal cortex (FC), AMY, and hippocampus (HIP) but not in STR or spinal cord. Pretreatment with MK801 blocked this effect of naltrexone in AMY but not in NA, FC, or HIP, while pretreatment with LY274614 or clonidine blocked this effect of naltrexone in AMY and NA but not in FC or HIP. These results further delineate both the neuroanatomical pathways involved in morphine withdrawal and the locus of action of compounds that reduce morphine-withdrawal symptoms.

Animals↗
PubMed1995

QRS prolongation as an indicator of risk of ischemia-related ventricular tachycardia and fibrillation induced by exercise.

The majority of patients with serious ventricular arrhythmias induced by exercise have ischemic heart disease. These arrhythmias, however, develop only in a minority of the patients with coronary artery disease. The aim of this study was to investigate whether patients with ventricular tachycardia or fibrillation produced by exercise-induced ischemia exhibit any premonitory electrocardiographic indicators of arrhythmia propensity and whether arrhythmia suppression by myocardial revascularization abolished these changes. High-quality exercise electrocardiograms (50 mm/sec) from 30 case patients with ventricular tachycardia and fibrillation produced by exercise-induced ischemia were studied before and after surgical revascularization. These results were compared with those obtained from 30 control patients matched for age, sex, heart disease, and preoperative exercise capacity. The resting and peak exercise electrocardiograms were examined separately in a blinded manner with respect to QRS duration, ST-segment depression, and JT intervals. Patients with bundle branch block patterns were excluded. The QRS duration at rest was similar in case and control patients preoperatively and increased significantly with exercise in both groups. However, the QRS prolongation was larger in the case group, in which it was 11 +/- 3 msec compared with 4 +/- 2 msec in the control group (p = 0.043). QRS prolongation > or = 15 msec predicted ischemia-related ventricular arrhythmias in 73% of the patients. After surgical revascularization, there was no QRS prolongation with exercise in either group. In both groups, the QRS prolongation was associated with significant ST-segment depression, which was larger in the case patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Case-Control Studies↗
PubMed1995

Pattern of coronary artery disease in patients with ventricular tachycardia and fibrillation exposed by exercise-induced ischemia.

The majority of patients with serious exercise-induced ventricular arrhythmias have extensive coronary artery disease. These arrhythmias develop, however, only in a minority of patients with angina pectoris. The purpose of the present study was therefore to investigate whether these arrhythmia patients are characterized by any specific "arrhythmogenic" pattern of coronary artery disease. Among 1100 consecutive patients undergoing coronary artery bypass grafting, 30 (2.7%) patients had ventricular tachycardia or fibrillation during preoperative exercise testing. For each of these patients, two matched controls with angina pectoris but no ventricular arrhythmia were selected. All patients underwent angiocardiography by standard techniques. The recordings were blinded and interpreted in random order by an experienced invasive cardiologist. Significant stenosis (> or = 50%) of the main left coronary artery was found in 27% of the case patients compared to 12% of the matched controls (p = 0.069, two-tailed t test); proximal left anterior descending artery stenoses were more frequent in the arrhythmia patients. Although stenosis > or = 75% was only moderately more frequent in the case patients, the difference was highly significant for stenosis > or = 95%, which was seen in 47% of the case patients compared to 22% of the controls (p = 0.015). The difference was even more pronounced for the combination of main left coronary artery stenosis and/or high-grade stenosis (> or = 95%) of the left anterior descending artery. This pattern was seen in 60% of the case patients compared to 28% of the matched controls (p = 0.004).(ABSTRACT TRUNCATED AT 250 WORDS)

Angiocardiography↗
PubMed1995

Selection of medical treatment in stable angina pectoris: results of the International Multicenter Angina Exercise (IMAGE) Study.

OBJECTIVES: The present study was designed to investigate which characteristics of anginal symptoms or exercise test results could predict the favorable anti-ischemic effect of the beta-adrenergic blocking agent metoprolol and the calcium antagonist nifedipine in patients with stable angina pectoris. BACKGROUND: The characteristics of anginal symptoms and the results of exercise testing are considered of great importance for selecting medical treatment in patients with chronic stable angina pectoris. However, little information is available on how this first evaluation may be used to select the best pharmacologic approach in individual patients. METHODS: In this prospective multicenter study, 280 patients with stable angina pectoris were enrolled in 25 European centers. After baseline evaluation, consisting of an exercise test and a questionnaire investigating patients' anginal symptoms, the patients were randomly allocated to double-blind treatment for 6 weeks with either metoprolol (Controlled Release, 200 mg once daily) or nifedipine (Retard, 20 mg twice daily) according to a parallel group design. At the end of this period, exercise tests were repeated 1 to 4 h after drug intake. RESULTS: Both metoprolol and nifedipine prolonged exercise tolerance over baseline levels; the improvement was greater in the patients receiving metoprolol (p < 0.05). Multivariate analysis revealed that low exercise tolerance was the only variable associated with a more favorable effect within each treatment group. Metoprolol was more effective than nifedipine in patients with a lower exercise tolerance or with a higher rate-pressure product at rest and at ischemic threshold. None of the characteristics of anginal symptoms or exercise test results predicted a greater efficacy of nifedipine over metoprolol. CONCLUSIONS: The results of a baseline exercise test, but not the characteristics of anginal symptoms, may offer useful information for selecting medical treatment in stable angina pectoris.

Angina Pectoris↗
PubMed1995

The role of the locus coeruleus and N-methyl-D-aspartic acid (NMDA) and AMPA receptors in opiate withdrawal.

Biochemical, behavioral, and electrophysiologic studies indicate that activation of the noradrenergic cells in the locus coeruleus (LC) plays an important role in the symptoms of opiate withdrawal. Extrinsic factors play a major role in the morphine-withdrawal-induced activation of the LC, but intrinsic factors also play a role. Among the extrinsic factors, a glutamatergic projection from the nucleus paragigantocellularis plays an important role in the withdrawal-induced activation of the LC. N-methyl-D-aspartic acid (NMDA) receptors play at most a minor role in the withdrawal-induced activation of the LC by glutamate; preliminary evidence indicates that alpha-amino-3 hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors play an important role. Whereas NMDA antagonists produce little to no suppression of the activation of the LC during morphine withdrawal, they do suppress many morphine withdrawal symptoms. However, phencyclidinelike side effects may limit the clinical utility of NMDA antagonists. Experiments examining c-fos expression during morphine withdrawal indicate that NMDA antagonists may exert some of their influence on morphine withdrawal symptoms through actions in the forebrain. Pretreatment with the noncompetitive NMDA antagonist MK801 blocks morphine withdrawal-induced increased c-fos expression in the amygdala, but not in the nucleus accumbens, frontal cortex, or hippocampus. Pretreatment with the competitive NMDA antagonist LY274614 (or the alpha2-adrenergic agonist clonidine) blocks morphine withdrawal-induced increased c-fos expression in the amygdala and nucleus accumbens, but not in the frontal cortex or hippocampus. These results help to elucidate some of the neuroanatomy and neurophysiology underlying morphine withdrawal. Further, NMDA antagonists may not be clinically useful for opiate withdrawal due to their side-effects, but AMPA antagonists may be of great benefit for alleviating opiate withdrawal symptoms in humans.

Animals↗