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Biomedical subjects

F Fyhrquist

Publications and source records attributed to F Fyhrquist.

At least 145 records · Page 8Linked to original sources
PubMed1987

The effect of dexamethasone on the enteroinsular axis.

In order to examine whether hyperinsulinaemia induced glucocorticoid therapy involves alterations of the enteroinsular axis glucose, insulin, C-peptide, glucagon and GIP responses to a test meal with and without prior intake of dexamethasone (2 + 2 mg) in 13 healthy subjects were measured. Dexamethasone caused impaired glucose tolerance, which was associated with an exaggerated insulin (0.61 +/- 0.05 vs. 0.38 +/- 0.05 nmol/l; p less than 0.001). C-peptide (0.97 +/- 0.08 vs. 0.71 +/- 0.06 nmol/l; p less than 0.001) and glucagon response to a test meal. In contrast, the GIP response to the test meal was blunted after dexamethasone (126 +/- 17 vs. 177 +/- 23 pmol/l; p less than 0.001). It therefore follows that alterations in the enteroinsular axis, that is, GIP secretion, cannot be responsible for the enhancement of insulin secretion observed after dexamethasone. The mechanism(s) for the decreased GIP response after dexamethasone could involve (1) a direct inhibitory effect on GIP secretion by dexamethasone, and/or (2) a negative feedback of elevated glucose and insulin levels on GIP secretion.

Adult↗
PubMed1986

Acute hemodynamic and hormonal effects of lisinopril (MK-521) in congestive heart failure.

The acute hemodynamic and hormonal effects of the oral angiotensin-converting enzyme (ACE) inhibitor lisinopril (MK-521) were assessed over a period of 96 hours in 12 patients with heart failure. This compound is the lysine analogue of enalaprilat (MK-422), is biologically active following absorption, and is cleared via the urine without any known metabolic transformation. Single doses of lisinopril, ranging from 1.25 mg to 10 mg, were administered on days 1 and 3, each followed by 48 hours of intensive hemodynamic observation. Across all doses, maximal reductions in mean arterial pressure (17.2%), mean pulmonary capillary wedge pressure (28%), and systemic vascular resistance (25.6%) were observed compared to baseline values. No significant changes in heart rate were recorded. Arterial blood was sampled at frequent intervals for angiotensin II, ACE activity, plasma renin activity, renin substrate, plasma aldosterone, and serum drug levels. Right atrial blood was sampled simultaneously for angiotensin I, thus permitting assessment of the degree of pulmonary conversion to angiotensin II. The results indicate potent inhibition of the renin-angiotensin-aldosterone system along with hemodynamic efficacy over a period exceeding 24 hours. Frequent clinical follow-up on long-term chronic therapy has revealed no adverse experience.

Adult↗
PubMed1986

Cerebrospinal fluid lysozyme and beta 2-microglobulin in neurosarcoidosis.

The levels of lysozyme (LZM) and beta 2-microglobulin (beta 2m) were measured in the cerebrospinal fluid (CSF) and serum of 32 patients with sarcoidosis, 20 of whom had neurosarcoidosis. LZM was analyzed by a new radioimmunoassay (RIA) modification. CSF LZM was elevated in 15 of 20 patients with neurosarcoidosis but in only 4 of 12 patients with extraneural sarcoidosis. CSF beta 2m values were elevated in 13 of 19 and in one of 11 patients, respectively. In neurosarcoidosis, both CSF LZM and beta 2m correlated to CSF leucocytes but not significantly to CSF albumin thus suggesting that LZM and beta 2m were secreted from cells within the central nervous system (CNS). In patients with sarcoidosis, elevations of CSF LZM and beta 2m revealed disease activity in the CNS. Both analyses were also useful in the follow-up of neurosarcoidosis.

Adult↗
PubMed1986

Continuous infusion of fentanyl or alfentanil for coronary artery surgery. Effects on plasma cortisol concentration, beta-endorphin immunoreactivity and arginine vasopressin.

Plasma cortisol, beta-endorphin immunoreactivity (PBEir) and arginine vasopressin (AVP) responses during and after the continuous infusion of fentanyl or alfentanil were studied in 19 patients undergoing coronary artery bypass grafting (CABG). Plasma cortisol concentration decreased significantly in both groups during the anaesthesia and surgery before cardiopulmonary bypass (CPB); an increase was evident during CPB in both groups, but a statistically significant increase was not observed during the rest of the study, including the awakening from anaesthesia. PBEir increased with both opiates immediately after initiation of CPB and remained so during the rest of the study. There were no significant changes in plasma AVP concentrations during anaesthesia and surgery. After discontinuation of opiate infusions, an increase in AVP concentration commenced earlier in the alfentanil group than in the fentanyl group. At awakening from anaesthesia, a significant correlation was observed between log plasma AVP concentration and systemic vascular resistance. It is concluded that, with continuous fentanyl and alfentanil infusions in a total dose relationship of 1:13 in patients undergoing CABG, cortisol and AVP responses to surgery and CPB can be suppressed. However, during recovery from anaesthesia, the attenuating effect of alfentanil seems to wear off more rapidly than that of fentanyl. PBEir response to CPB and emergence from anaesthesia could not be prevented with either analgesic.

Adult↗
PubMed1986

Competitive inhibitor binding assay (CIBA) of ACE inhibitors.

We describe a new principle for measuring concentrations of pharmacologically active captopril or other angiotensin-converting enzyme (ACE) inhibitors in blood. Serum is incubated with 125-I-labeled ACE inhibitor (substance 351A, a lisinopril analogue, Merck Sharp & Dohme) in a nonequilibrated system, in which label and ACE inhibitor compete for binding to added serum ACE. Free label is separated by adsorption to coated charcoal. Concentration of captopril or other ACE inhibitor is calculated from a standard curve. Results in healthy volunteers showed rapid absorption of captopril with maximal concentration of active drug within 1 h, and fast disappearance within 2.5 h. Stability of captopril was improved by immediate 1:100 dilution of blood samples with assay buffer. In spite of this precaution, analysis should be performed within two days to avoid loss of active drug due to polymerization and protein binding. Samples of other tested ACE inhibitors can be frozen and later analyzed at convenience. The new principle is simple, sensitive, and specific.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1986

Antidiuretic hormone and atrial natriuretic peptide in congestive heart failure.

Plasma concentrations of antidiuretic hormone (ADH) were measured in 8 patients with congestive heart failure (CHF) of NYHA functional class III-IV, before and during treatment with captopril, 6.25-25.0 mg t.i.d., added to their drug regimen. Before captopril treatment, plasma ADH was high, 2.5 times the upper limit of normal reference values. During treatment with captopril, plasma ADH levels were normalized, and remained so throughout the study, for at least 6 months. Plasma levels of angiotensin II were also reduced to a normal level. Reduction of plasma ADH during captopril treatment in CHF may partly depend on reduced angiotensin II formation, and may be beneficial by improving water balance. Atrial natriuretic peptide (ANP), was measured by radioimmunoassay in 17 patients with CHF. The highest levels were measured in the most severe CHF cases, and intermediate high values on NYHA functional class I-II patients. Plasma ANP concentrations in control patients (n = 18) without cardiac diseases ranged between 0 and 30 pg/ml. In two patients with paroxysmal supraventricular tachycardia, associated with transient polyuria, high plasma ANP concentrations were noticed during tachycardic episodes. Thus, ANP appears to be a circulating hormone in humans, and is released into the blood in clinical conditions associated with raised preload and atrial wall stretch.

Aged↗
PubMed1986

Angiotensin-converting enzyme in sarcoid and chalazion granulomas of the conjunctiva.

Angiotensin-converting enzyme (ACE) was studied immunohistochemically in conjunctival biopsies from 6 patients with systemic sarcoidosis, 4 patients with posterior non-sarcoid uveitis and in specimens from 4 patients with chalazion of the eyelid. Specimens with sarcoid granulomas showed intense ACE-positive immunoreactivity in epitheloid cells of the granuloma, whereas chalazion granulomas did not contain ACE-immunoreactivity. There was no difference in staining patterns between specimens without granulomas. Thus immunohistochemical staining for ACE may be of help in differentiating conjunctival granulomatous tissue of a chalazion from sarcoid granuloma.

Conjunctival Diseases↗
PubMed1986

Effects of acarbose on the relationship between changes in GIP and insulin responses to meals in normal subjects.

The relationship between changes in gastric inhibitory polypeptide (GIP), C-peptide and insulin responses to meals was studied in 8 normal subjects after 2 weeks of Acarbose treatment. Acarbose caused a significant reduction of GIP and insulin responses (P less than 0.05). The decrease in insulin response could not be explained by changes in the glycaemic stimulus of insulin secretion, as Acarbose did not significantly change the plasma glucose response to meals during the study. The reduced insulin response was seen without a concomitant reduction in the C-peptide response to the meals, thus resulting in a decreased insulin/C-peptide ratio after Acarbose treatment (P less than 0.05). The changes in GIP response after Acarbose correlated positively with the change in insulin/C-peptide ratio (r = 0.69; P less than 0.05). Our data thus challenge the concept that Acarbose therapy affects the secretion of insulin. The positive relationship between changes in GIP response and changes in the insulin/C-peptide ratio rather suggests that GIP affects the metabolism of insulin or C-peptide.

Acarbose↗
PubMed1986

Clinical pharmacology of the ACE inhibitors.

The central role of the renin-angiotensin-aldosterone system in the regulation of fluid balance and haemodynamics was not fully appreciated until the discovery and clinical application of inhibitors of the angiotensin-converting enzyme (ACE). Captopril, the first orally active compound has proved to be highly effective in mild, intermediate and severe hypertension and in congestive heart failure. This is also true for enalapril, the first of the second generation (non-sulfhydryl) of ACE inhibitors. Both compounds combine a high degree of clinical efficacy with a low rate of side effects, and both are eliminated via renal excretion. Thus, reduced doses are required in renal failure. Captopril has a shorter half-life and requires more frequent dosing than enalapril. Whether long-acting ACE inhibitors carry distinct advantages or disadvantages compared with short-acting ones is not clear, but both possibilities must be considered. Among many new ACE inhibitors being developed, compounds eliminated via hepatic routes, such as fosfenopril and zofenopril, may prove advantageous in renal failure. Very long-acting ones, such as lisinopril, a potent ACE inhibitor already shown to be clinically effective, may add value to this group of therapeutic agents. Drug compliance may be easily tested by measuring ACE activity in serum from patients treated with stable ACE inhibitors, such as enalapril and lisinopril, which is an obvious advantage compared with other antihypertensive compounds. The presence of ACE in sites not associated with regulation of fluid balance or blood pressure, such as macrophages and reproductive organs, and the possibility that new functions of ACE may be discovered, call for vigilance regarding possible long term side effects of ACE inhibitors.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1986

Relationship between changes in GIP concentrations and changes in insulin and C-peptide concentrations after guar gum therapy.

In order to elucidate the mechanisms of the action of gel-forming fibre in diabetes, we measured insulin, C-peptide and GIP responses to meals during treatment with guar gum and placebo in normal and non-insulin-dependent diabetic (NIDD) subjects. Dietary supplementation with guar gum caused a sustained reduction of the GIP response in normal and diabetic subjects (p less than 0.05), but did not influence insulin responses. On the other hand, guar gum increased the C-peptide response to meals in normal subjects (p less than 0.05) resulting in a 40% decrease of the insulin/C-peptide ratio (p less than 0.01). Assuming that the insulin/C-peptide ratio reflects the hepatic extraction of insulin, this would be compatible with increased hepatic removal of insulin. The change in insulin/C-peptide ratio was positively correlated with the change in GIP response after guar gum (r = 0.75; p less than 0.001) and this correlation was strengthened in normal subjects (r = 0.91; p less than 0.001). Our data thus suggest that guar gum stimulates rather than suppresses insulin secretion. The apparent insulinotropic action of GIP may partly be explained by a reduced hepatic extraction of insulin.

Adult↗
PubMed1985

Plasma atrial natriuretic peptide in cardiac disease and during infusion in healthy volunteers.

Plasma concentrations of immunoreactive atrial natriuretic peptide (ANP) were low or undetectable in 8 healthy subjects and 9 control patients without cardiac disease, and raised in 17 patients with congestive heart failure (CHF). Highest concentrations were measured in patients with severe CHF. High plasma ANP levels were also found in 2 patients with paroxysmal supraventricular tachycardia and associated transient polyuria. Infusion of synthetic human alpha-ANP, 110-125 micrograms over 30 min, to 3 healthy males resulted in a 2.3-fold increase in natriuresis and diuresis but had no effect on kaliuresis. Plasma levels of renin activity, aldosterone, and antidiuretic hormone did not change significantly. ANP infusion gave plasma ANP levels of the same magnitude as those found in severe CHF; levels returned to baseline within 15 min of stopping the infusion. Thus ANP appears to be a circulating hormone in man, at least in severe CHF and supraventricular tachycardia.

Adult↗
PubMed1985

Thyroid hormones affect serum angiotensin I converting enzyme levels.

Serum angiotensin I converting enzyme (ACE) was measured in 10 patients with Graves' disease and 2 with thyroiditis during different stages of the diseases. The effect of thyroxine on serum ACE levels was also recorded in 12 patients with thyroid cancer, who were on thyroxine suppression. Serum ACE levels correlated positively with clinically assessed thyroid function and peripheral thyroid hormone levels, especially during hyper- or hypofunction. ACE was measured both with an enzyme kinetic and a new, quantitative inhibitor binding assay. The methods gave similar results, which indicates that ACE increments during thyroid hyperfunction were quantitative, and not a result of increased enzyme activity. Serum ACE increments associated with high lysozyme concentrations are signs of immunologic activation or proliferation of monocytic cells. In this study there was no correlation between the two enzymes, which may indicate either increased synthesis or possibly shedding of ACE from endothelial cells or delayed metabolic clearance of this enzyme. Serum ACE measurements may provide a useful tool for assessing thyroid function and the effect of thyroxine treatment.

Adolescent↗
PubMed1985

Systemic manifestations and enzyme studies in sarcoidosis with neurologic involvement.

The dissemination and activity of systemic disease was evaluated retrospectively in 50 patients with neurosarcoidosis, 24 of whom presented with neurologic symptoms. During follow-up, five patients never developed detectable systemic disease. In 26 patients, sarcoidosis had previously been diagnosed, but in 11 (42%) of them the neurologic symptoms were initially not connected with this disease. During follow-up, extraneural features were those of sarcoidosis in general. However, 23 patients (46%) had normal chest X-ray on admission to neurologic examinations. Fourteen (35%) of 40 examined patients had ocular changes, 13 (33%) of 39 hypercalciuria and 13 (26%) of 50 skin manifestations. Serum angiotensin converting enzyme (ACE) was elevated in only 31% of the patients. Measureable amounts of ACE were recorded in the cerebrospinal fluid from 13 of 17 examined patients. During follow-up the activity of neurosarcoidosis seemed to be linked to the course of systemic disease in general.

Adolescent↗