Biomedical subjects

E P Corssmit

Publications and source records attributed to E P Corssmit.

At least 19 recordsLinked to original sources

PubMed2003

[Subclinical hyperthyroidism: not necessarily a thyroid disorder].

Three women, aged 16, 70 and 72 years, were seen in our outpatients' clinics with a decreased TSH value. In two of them, thyroid dysfunction was not the cause of the low TSH activity. In patient A, the cause was diminished food intake and in patient B, who was also known with nodular thyroid disease, the cause was the use of glucocorticoids. Only patient C had subclinical hyperthyroidism due to goitre with concomitant atrial fibrillation. She was recommended for treatment with 131I. Patients A and B recovered spontaneously. Subclinical hyperthyroidism is being increasingly encountered due to the availability of sensitive assays for measuring TSH activity and the increased frequency with which general practitioners test thyroid function. However, in about 55% of cases suppressed TSH values normalise spontaneously. This means that it is important to establish if thyroid disease is truly present. The treatment of subclinical hyperthyroidism should be initiated on the basis of individual data.

Adolescent↗

PubMed2003

[Subclinical functional disorders of the thyroid gland].

Subclinical hypothyroidism is associated with aspecific complaints such as tiredness, cognitive and depressive complaints, subtle disturbances in lipid values, an increased risk of cardiovascular disease, ovulatory dysfunction and a negative effect on foetal psychomotor development and pregnancy outcome. Subclinical hyperthyroidism is associated with atrial fibrillation, osteoporosis and dementia. Not enough prospective randomised studies with hard outcomes are available to provide evidence-based general recommendations. Therefore, the decision as to whether or not a patient should be treated needs to be made on an individual basis. For subclinical hypothyroidism it is advisable to consider treatment in the case of positive thyroid peroxidase antibody tests, a TSH concentration higher than 10 mU/l, the presence of one or more risk factors for cardiovascular disease, infertility on the basis of ovulatory dysfunction, and pregnancy. In the case of complaints of tiredness and certainly in the case of depression or cognitive dysfunction, a 3-month trial treatment can be considered. This leads to a decrease of the complaints in about 25% of cases. As negative effects are associated with the treatment, we advise an expectant approach in all other cases with a yearly monitoring of the TSH concentration. For subclinical hyperthyroidism it is advisable to consider treatment in the case of a nodular goitre, and especially in the case of atrial fibrillations. If subclinical hyperthyroidism persists in the absence of nodular thyroid disease, an expectant approach appears to be justified.

Depression↗

PubMed2001

[Timely recognition and treatment of hypothyroidism in pregnant women: benefit for the child].

Three women aged 36, 34 and 33 years, with primary hypothyroidism were euthyroid whilst on levothyroxine treatment. Two women had previously received 131iodine therapy due to Graves' disease. During pregnancy the levothyroxine dose required to maintain a normal TSH level increased. The serum TSH-binding inhibiting immunoglobulins (TBII) activity was still very high (188 U/l) in one of the women, but decreased to 26 U/l in the last trimester. Foetal or neonatal thyrotoxicosis was not observed. The levothyroxine dose was decreased after delivery and none of the women experienced any adverse effects as a result of this. It is recommended that all women taking levothyroxine should have their serum TSH activity measured during the first trimester. The daily dose of levothyroxine required will usually increase by 50 micrograms during pregnancy. The determination of serum TBII activity is indicated in the case of Graves' disease; serum TBII values of > 40 U/l constitute a risk of foetal or neonatal thyrotoxicosis.

Adult↗

PubMed2001

[Pregnancy (conception) in hyper- or hypothyroidism].

Pregnancy is accompanied by changes in thyroid function. Due to the increased synthesis of thyroid binding globulin and the thyroid-stimulating effect of human chorionic gonadotrophin (hCG), serum concentrations of thyroid hormones will increase in the first trimester of pregnancy (total T4, T3). Free T4 levels decrease during the latter half of pregnancy. Hyperthyroidism during pregnancy is usually due to Graves' disease. Definitive therapy may be considered for cases prior to pregnancy, although a medical management as would be given during pregnancy is an equally good option. The medical management of hyperthyroidism consists of a monotherapy with thyreostatics in which the recommended dose needs to be adjusted on the basis of free T4 in the high-normal and thyroid stimulating hormone (TSH) in the low-normal area so as to minimise the risk of foetal hypothyroidism. The transplacental passage of maternal TSH receptor stimulating antibodies may cause foetal hyperthyroidism. Another cause of maternal hyperthyroidism during pregnancy is 'gestational transient thyrotoxicosis', which is associated with high hCG levels during the first trimester of pregnancy. It is nearly always accompanied by hyperemesis gravidarum. Hypothyroidism in pregnancy has negative consequences for the foetus. If the hypothyroidism is apparent prior to pregnancy, it should be corrected before conception (target TSH value of 1 mU/l). If discovered during pregnancy, treatment with levothyroxine should be started as soon as possible. In the case of a pre-existing hypothyroidism a 25-50% increase in the levothyroxine dosage is often needed during the first trimester of pregnancy. This is possibly due to an increased requirement. An adequate serum concentration of T4 is necessary for foetal brain development.

Adult↗

PubMed2001

Review article: Regulation of glucose production with special attention to nonclassical regulatory mechanisms: a review.

Hepatic glycogenolysis and gluconeogenesis are essential processes for the prevention of hypoglycemia during short-term starvation. As has been calculated from stable isotope studies, gluconeogenesis accounts for approximately 35% to 50% of total basal glucose production, glycogenolysis for the other 50% to 65%. In long-term starvation, the kidney also contributes to glucose production by gluconeogenesis. Glucose production is regulated by the interaction of different regulatory mechanisms, eg, by glucoregulatory hormones, glucose itself, and gluconeogenic substrates. In the last decades, more insight has been gained into the importance of the autonomous nervous system and the existence of an extensive paracrine network in the liver that seems to exert a potent glucoregulatory role as well. This review is focused on the regulation of hepatic glucose production by the autonomous nervous system and the paracrine network, with special emphasis on studies carried out in human subjects.

Autonomic Nervous System↗

PubMed2000

Indomethacin decreases insulin secretion in patients with type 2 diabetes mellitus.

In healthy subjects, basal endogenous glucose production (EGP) is partly regulated by paracrine intrahepatic factors. Administration of indomethacin, an inhibitor of prostaglandin synthesis, resulted in a transient stimulation of EGP without changes in glucoregulatory hormone concentrations. It is unknown whether similar paracrine factors influence basal EGP in type 2 diabetes mellitus. The effects of 150 mg indomethacin, a nonendocrine stimulator of glucose production in healthy adults, and placebo on EGP were measured in a randomized placebo-controlled study in patients with type 2 diabetes mellitus (3 men and 3 women; mean age, 58.5 years; mean body mass index, 28.6 kg x m(-2)). EGP was measured before and for 6 hours after administration of placebo/indomethacin, by a primed, continuous infusion of [6,6-2H2]glucose. After indomethacin, plasma glucose and EGP increased in all subjects by 14% (P < .05) and 48% (P < .05), respectively. In the control experiment, plasma glucose and EGP declined gradually in all subjects by 22% (P < .001) and 17% (P = .004), respectively. The stimulation of glucose production coincided with the inhibition of insulin secretion by 52% within 1 hour after administration of indomethacin (P < .001). In the control experiment, insulin secretion decreased gradually by 18% after 6 hours (P < .001). Thus, indomethacin inhibits insulin secretion and stimulates EGP in type 2 diabetes.

Adult↗

PubMed2000

Biologic responses to IFN-alpha administration in humans.

Although interferon-alpha (IFN-alpha) was discovered over 40 years ago, it was many years before it was registered as a therapeutic agent. Because of its unique qualities, it has been registered for both antiviral and antitumor indications. In addition to its therapeutic effects in viral diseases and cancer, IFN-alpha interferes with several important physiologic systems. It interacts with the immune system and affects several neuroendocrine and metabolic circuits. The specific mechanisms by which IFN-alpha exerts its therapeutic effects are complex, and it is very difficult to tie the biologic actions of IFN-alpha to specific clinical effects.

Antineoplastic Agents↗

PubMed2000

Administration of interferon-gamma in healthy subjects does not modulate thyroid hormone metabolism.

Cytokines, such as tumor necrosis factor-alpha (TNF-alpha), interleukin (IL-2), IL-6, and interferon-alpha (IFN-alpha), alter human thyroid hormone metabolism and may be involved in the pathogenesis the euthyroid sick syndrome. Experimental data suggest that interferon-gamma (IFN-gamma) could be another cytokine that might influence thyroid hormone metabolism. To evaluate whether IFN-gamma can be involved in the pathogenesis of the alterations in thyroid hormone metabolism in humans with nonendocrine illness, we measured thyroid hormone concentrations in six healthy volunteers during 24 hours in a placebo controlled trial: once after subcutaneous administration of IFN-gamma (Immukine, [Boehringer Ingelheim GmbH, Ingelheim/Rheim, Germany] 100 microg/m2 subcutaneous) and once after the administration of saline (control). In addition, we measured cytokine concentrations in plasma (TNF-alpha and IL-6). IFN-gamma did not induce effects on any of the measured thyroid hormone and thyroid-stimulating hormone (TSH) plasma concentrations. Moreover, IFN-gamma did not affect TNF-alpha plasma levels. Only a modest but significant elevation of plasma IL-6 levels was detected after administration of IFN-gamma (p < 0.05 vs. control). It is concluded that IFN-gamma administration to healthy humans does not result in short term alterations of thyroid hormone metabolism. These data do therefore not support a role of IFN-gamma in the pathogenesis of the euthyroid sick syndrome in humans as might be deduced from in vitro and in vivo animal studies.

Body Temperature↗

PubMed2000

Acute effects of interferon-alpha administration on testosterone concentrations in healthy men.

OBJECTIVE: Recombinant human interferon alpha (rhIFN-alpha) is used therapeutically in malignant disorders and chronic hepatitis. The present study was assessed to study the effects of rhIFN-alpha on the hypothalamic-pituitary-testicular (HPT) axis. DESIGN AND METHODS: We performed a saline-controlled cross-over study in six healthy men, sequentially measuring the serum concentrations of gonadotropins, testosterone, the free androgen index (FAI) and sex hormone-binding globulin (SHBG) after a bolus subcutaneous injection of rhIFN-alpha. RESULTS: rhIFN-alpha induced a sustained decrease of both testosterone (from 19.5+/-1.88 to a nadir of 5.49+/-0.51nmol/l at the end of the study) and FAI (from 98.7+/-14.7 to a nadir of 32. 1+/-5.3 at the end of the study), whereas concentrations of LH, FSH and SHBG were not different between the two studies. CONCLUSIONS: Our results suggest that rhIFN-alpha affects the HPT axis at the testicular level, either directly or indirectly, and changes feedback relationships between the pituitary and the testis.

Adult↗

PubMed1999

Löffler's endomyocarditis in the idiopathic hypereosinophilic syndrome.

The idiopathic hypereosinophilic syndrome (HES) is a leukoproliferative disorder characterized by sustained eosinophilia (> 1.5 x 10(9)/l) and (multi-)organ dysfunction caused by infiltration of eosinophils. Especially the heart is frequently affected. In this report, we describe 2 patients with HES and Löffler's endomyocarditis. Prednisone is the drug of choice for treatment. Both our patients responded very well to prednisone and came into remission. If prednisone fails, there are other therapeutic options like myelosuppressive drugs (hydroxyurea and vincristine) or interferon-alpha. We review the literature with regard to clinical presentation, diagnosis and treatment.

Adult↗

PubMed1998

[Chest pain and electrocardiogram abnormalities: consider pulmonary embolism].

Pulmonary embolism is a serious and potentially life-threatening disease that requires early recognition and treatment. In three patients, two men aged 60 and 61 and a woman aged 76, prominent severe chest pain and electrocardiographic changes suggesting ischaemic heart disease, lack of response to treatment, marked dyspnoea and haemodynamic instability eventually led to the clinical suspicion and subsequent diagnosis of pulmonary embolism. Electrocardiographic changes are indicative of right-sided overload and sometimes of arterial hypoxaemia. Although ECG changes are very frequent in cases of pulmonary embolism, the abnormalities observed are mostly nonspecific ST-T segment changes.

Chest Pain↗

PubMed1997

Differential effects of enzyme supplementation therapy on manifestations of type 1 Gaucher disease.

BACKGROUND: In type 1 Gaucher disease (GD), the accumulation of glucocerebroside in macrophages, caused by deficient activity of glucocerebrosidase, results in a variety of disease manifestations. In addition to the characteristic features of hepatosplenomegaly, cytopenia, and bone abnormalities, resting energy expenditure (REE) and glucose production are increased. In this study the effects of enzyme supplementation therapy on metabolic parameters in relation to other disease manifestations in type 1 GD patients are investigated. PATIENTS AND METHODS: In 12 adult type 1 GD patients, measurements of REE (by indirect calorimetry), liver and spleen volume (by spiral computerized axial tomography [CT]) and hemoglobin and platelet count were obtained before and after 6 months of alglucerase therapy (15 U/kg per month). In 7 of the 12 patients hepatic glucose production was measured by infusing 3-3H glucose. For comparison, REE and glucose metabolism were studied in 7 weight- and age-matched healthy subjects. RESULTS: REE and glucose production were increased in GD patients as compared with controls (REE: 29.8 kcal/kg/24 h +/- 3.6 and 23.1 +/- 2.3 kcal/kg/24 h, respectively, P < 0.05; glucose production: 14.00 mumol/kg/min +/- 0.51 and 10.77 mumol/kg/min +/- 0.26, respectively, P < 0.03). There were no differences in plasma glucose concentrations. Whereas the elevated REE decreased after 6 months of alglucerase therapy from 129% to 120% of predicted values (P < 0.01), the increase in hepatic glucose production did not change. An increase in weight occurred after 6 months of treatment (1.7 +/- 0.8 kg, P < 0.001), which was accounted for by an increase in fat mass of 1.6 +/- 1.5 kg (P < 0.02). Hemoglobin levels increased from 11.2 mg/dL to 12.1 mg/dL (P = 0.05) and platelet counts rose from 84 x 10(9)/L to 113 x 10(9)/L (P < 0.05). Although liver and spleen volumes decreased by approximately 10% and approximately 20%, respectively, there was no correlation between the decrease in organ volumes and the decrease in REE. CONCLUSIONS: Treatment with alglucerase improves hypermetabolism and organomegaly in GD, whereas the increase in glucose production persists. Therefore, the dose-response effects of alglucerase are variable for the different manifestations of type 1 GD.

Adult↗

PubMed1997

Effects of interferon-alpha (IFN-alpha) administration on leucocytes in healthy humans.

Plasma concentrations of IFN-alpha are increased in several inflammatory conditions. Several lines of evidence indicate that IFN-alpha has anti-inflammatory properties. To study the effects of IFN-alpha on leucocyte subsets and activation and on cytokines, we administered IFN-alpha (rhIFN-alpha2b; 5 x 10(6) U/m2) to eight healthy human subjects in a randomized controlled cross-over study and analysed changes in circulating leucocytes and parameters for neutrophil and monocyte activation. After administration of IFN-alpha, neutrophil counts increased, monocyte counts decreased transiently, whereas the number of lymphocytes, basophils and eosinophils showed a sustained decrease. IFN-alpha administration was also associated with neutrophil activation, reflected in an increase in the plasma concentrations of elastase-alpha1-antitrypsin complexes and lactoferrin. Serum neopterin, a marker for monocyte activation, was significantly increased 10 h after administration of IFN-alpha. IFN-alpha significantly increased plasma concentrations of IL-6, IL-8 and IL-10. Although IL-1 and tumour necrosis factor (TNF) remained undetectable, plasma concentrations of soluble TNF receptors p55 and p75 increased after IFN-alpha administration. We conclude that IFN-alpha induces multiple alterations in the distribution and functional properties of leucocytes. IFN-alpha exerts pro- as well as anti-inflammatory effects within the cytokine network.

Adult↗

PubMed1997

Severe neurological complications in association with Epstein-Barr virus infection.

Involvement of the nervous system in infectious mononucleosis is common. About 50% have headache on presentation. Neck stiffness without meningitis is a frequent finding. Severe neurological complications are rare though, occurring in fewer than 0.5%. We describe two patients with unusual and severe neurological complications in association with serological evidence of EBV-infection: a 32-year old female developed a bilateral optic neuritis combined with a transverse myelitis and a 72-year old man developed mononeuritis multiplex, autonomic neuropathy and a salt-wasting nephropathy.

Adult↗

PubMed1996

Modulation of glucose production by indomethacin and pentoxifylline in healthy humans.

Indomethacin, an inhibitor of prostaglandin synthesis that modulates cytokine production, increases hepatic glucose output (HGO) in humans. However, prostaglandins stimulate glucose production in vitro. To investigate the mechanism of HGO stimulation by indomethacin, we compared the effect of pentoxifylline, an inhibitor of cytokine production, versus saline (study 1, n = 6) and of indomethacin versus the combination of indomethacin and pentoxifylline (study 2, n = 5) on basal HGO. HGO was measured by primed, continuous infusion of 3-3H-glucose. In study 1, pentoxifylline infusion resulted in an immediate, transient decrease of HGO of approximately 50% (from 12.9 +/- 0.4 to 6.0 +/- 1.7 micromol/kg/min after 15 minutes, P < .03 v control). There were no differences in concentrations of glucoregulatory hormones between the two experiments. In study 2, after indomethacin administration, HGO increased transiently by approximately 84% (from 9.7 +/- 0.7 at baseline to 16.7 +/- 2.4 micromol/kg/min after 135 minutes, P < .05). However, pentoxifylline did not affect the increase in HGO induced by indomethacin. There were no differences in concentrations of glucoregulatory hormones between the two experiments. Therefore, indomethacin stimulates HGO by mechanisms unrelated to glucoregulatory hormones, prostaglandins, or cytokines.

Adult↗

PubMed1996

Endocrine and metabolic effects of interferon-alpha in humans.

Interferon-alpha (IFN alpha) concentrations are increased in conditions associated with tissue injury. To investigate the endocrine and metabolic actions of IFN alpha in vivo, we studied eight healthy controls on two occasions, once after administration of 5 million units/m2 rhIFN alpha and once after administration of saline (control). Rates of appearance (Ra) of glucose and glycerol in plasma were measured by infusion of [3-3H]glucose and D5-glycerol, respectively. Energy expenditure and substrate oxidation were determined by indirect calorimetry. IFN alpha induced increases in plasma concentrations of norepinephrine (225 +/- 93%; P < 0.02 vs. control), epinephrine (272 +/- 80%; P < 0.05), cortisol (353 +/- 63%; P < 0.02), glucagon (50 +/- 12%; P < 0.05), free fatty acids (223 +/- 61%; P < 0.02), and glycerol (68 +/- 21%; P < 0.02) and in resting energy expenditure (36 +/- 50%; P < 0.03). The Ra of glycerol (169 +/- 39%; P < 0.02) and fat oxidation (104 +/- 23%, P < 0.02) were also increased after IFN alpha treatment. The Ra of glucose was higher at the end of the recombinant human IFN alpha treatment day than in the control experiment (12.83 +/- 1.08 vs. 9.34 +/- 0.46 mumol/kg.min; P < 0.03). It is concluded that IFN alpha administration induces, directly or indirectly, major endocrine and metabolic changes and is probably part of the cytokine network mediating the endocrine and catabolic reactions to tissue injury.

Adult↗

PubMed1996

Fibrinolytic response to interferon-alpha in healthy human subjects.

Interferons (IFNs) are used for a variety of disorders. It has been postulated that part of the effects of IFN may be mediated by IFN-induced modulation of endothelial cells. Since the principal activating and inhibiting factors of the fibrinolytic system are synthesized and stored in endothelial cells, we have studied the effects on fibrinolysis and coagulation of the administration of recombinant IFN-alpha (5 x 10(6) U/m2) to healthy human subjects (n = 8) in a randomized controlled cross-over study. IFN-alpha significantly increased plasma levels of tissue-type plasminogen activator (t-PA) and urokinase-type plasminogen activator (u-PA). Simultaneously, plasma levels of the inhibitor of plasminogen activation, PAI-1, sharply increased. The net effect on plasma plasminogen activator activity (PA-activity) was a modest increase to 116% of baseline, however without a significant effect on plasmin generation, as reflected by plasma levels of plasmin-alpha 2-antiplasmin complexes. IFN-alpha had no effect on the plasma levels of thrombin-antithrombin III (TAT) complexes. We conclude that despite considerable effects on endothelial cells, IFN-alpha does not significantly alter the coagulant-fibrinolytic balance, although the occurrence of such changes under pathological circumstances is not excluded.

Adult↗

PubMed1995

Soluble receptors for tumor necrosis factor are markers for clinical course but not for major metabolic changes in human immunodeficiency virus infection.

Tumor necrosis factor alpha (TNF) is a potential mediator of the metabolic changes in human immunodeficiency virus type 1 (HIV) infection. Soluble TNF receptor types I and II (sTNFR-I and -II) presumably reflect TNF activity. To examine the relationship between s TNFRs and host metabolism, resting energy expenditure (REE), body composition, and transferrin, albumin, triglyceride, retinol-binding protein, and sTNFR concentrations were measured in 12 asymptomatic and 18 symptomatic HIV-infected male subjects and 15 male control subjects. sTNFRs were increased in parallel with disease severity. REE was elevated approximately 8% in HIV-infected subjects (P = .005). REE correlated positively with fat free mass (FFM) and the presence of HIV infection, but not with sTNFRs. Inverse correlations existed between sTNFR-I or -II and albumin concentration (r = -.48, P = .007, and r = -.49, P = .006, respectively), between sTNFR-II and transferrin concentration (r = -.53, P = .003), and between In(sTNFR-II) and percent body fat (r = -.37, P < .05), but not between sTNFRs and triglyceride or retinol-binding protein. Thus, sTNFRs are markers for clinical course but not for major metabolic changes in HIV infection.

Adult↗