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J A Janssen

Publications and source records attributed to J A Janssen.

36 records · Page 2Linked to original sources

Serum total IGF-I, free IGF-I, and IGFB-1 levels in an elderly population: relation to cardiovascular risk factors and disease.

Recently, a method to measure free insulin-like growth factor-I (IGF-I) levels has been developed. Free IGF-I levels may have greater physiological and clinical relevance than total (bound and free) IGF-I. The associations between the circulating IGF-I/IGF binding protein (IGFBP) system and cardiovascular disorders was studied. In a cross-sectional study of 218 healthy persons (103 men, 115 women) aged 55 to 80 years, fasting serum (total and free) IGF-I and IGFBP-1 levels, lipid profile, insulin, and glucose were measured. In addition, blood pressure, body mass index (BMI), and waist-hip ratio (WHR) were measured. Ultrasonography of both carotid arteries was performed to investigate the presence of atherosclerotic lesions. A history of angina pectoris, the presence of a possible or definite myocardial infarction on the ECG, and plaques in the carotid arteries were used as indicators of presence of cardiovascular signs and symptoms. Free IGF-I was inversely related to serum triglycerides (P=.04, adjusted for age and sex). Mean free IGF-I levels in subjects without signs or symptoms of cardiovascular diseases were significantly higher than in those with at least one cardiovascular symptom or sign (P=.002, adjusted for age and sex). Free IGF-I levels were also higher in subjects who had no atherosclerotic plaques in the carotid arteries (P=.02, adjusted for age and sex) and who had never smoked (P=.02, adjusted for age and sex). IGFBP-1 showed an inverse relation with insulin, BMI, and WHR and a positive relation with HDL cholesterol. The associations between IGFBP-1 levels and HDL cholesterol, WHR, and BMI remained significant after adjustment for fasting insulin levels. High fasting serum free IGF-I levels are associated with a decreased presence of atherosclerotic plaques and coronary artery disease and lower serum triglycerides, whereas high fasting IGFBP-1 levels are associated with a more favorable cardiovascular risk profile. The findings suggest that the IGF-I/IGFBP system is related to cardiovascular risk factors and atherosclerosis.

Aged↗

Gender-specific relationship between serum free and total IGF-I and bone mineral density in elderly men and women.

OBJECTIVE: Little is known about the association between free IGF-I levels and bone mineral density (BMD). DESIGN: A cross-sectional study of 218 healthy subjects (103 men, 115 women, age 55-80 years) was carried out. METHODS: Fasting serum free IGF-I, total IGF-I, estradiol and sex hormone-binding globulin (SHBG) levels were measured. The ratio of estradiol to SHBG was used as an index of free estradiol. BMD measurements were performed by dual-energy X-ray absorptiometry of the lumbar spine and the proximal femur. RESULTS: In multivariate analyses with BMD of the lumbar spine as the dependent variable and serum free IGF-I, age, body mass index (BMI) and the free estradiol index as independent variables, the free IGF-I was positively related to the BMD of the lumbar spine in men (P = 0.02) but not in women. When the same analyses for the lumbar BMD were performed with total serum IGF-I the association was also only statistically significant in men (P = 0.05). In multivariate analyses with the trochanter BMD as the dependent variable and serum free IGF-I, total IGF-I, age, BMI and the free estradiol index as independent variables, the associations between (free and total) IGF-I and the trochanter BMD in men was of borderline significance. CONCLUSIONS: In elderly men free and total IGF-I were positively related to lumbar BMD, while (free and total) IGF-I was borderline positively related to trochanter BMD. As these relationships were not observed in elderly women, we suggest a weak gender-specific anabolic effect of IGF-I on BMD on trabecular bone.

Aged↗

Free and total insulin-like growth factor I (IGF-I), IGF-binding protein-1 (IGFBP-1), and IGFBP-3 and their relationships to the presence of diabetic retinopathy and glomerular hyperfiltration in insulin-dependent diabetes mellitus.

The existing literature on serum insulin-like growth factor I (IGF-I) levels in insulin-dependent diabetes mellitus (IDDM) is conflicting. Free IGF-I may have greater physiological and clinical relevance than total IGF-I. Recently, a validated method has been developed to measure free IGF-I levels in the circulation. Serum free and total IGF-I, IGF-binding protein-1 (IGFBP-1), and IGFBP-3 levels were measured in 56 insulin-treated IDDM patients and 52 healthy sex- and age-matched controls. Diabetic retinopathy was established by direct fundoscopy. In 54 IDDM patients, the glomerular filtration rate (GFR) and effective renal plasma flow were calculated from the clearance rate of [125I]iothalamate and [131I]iodohippurate sodium. Fasting free IGF-I, total IGF-I, and IGFBP-3 levels were significantly lower in IDDM patients than in age- and sex-matched healthy controls (free IGF-I, P < 0.005; total IGF-I, P < 0.001; IGFBP-3, P = 0.001), whereas IGFBP-1 levels were higher (P < 0.001). In IDDM subjects, decreases in free IGF-I, total IGF-I, and IGFBP-3 levels with age were observed (free IGF-I, r = -0.27 and P = 0.05; total IGF-I, r = -0.52 and P < 0.001; IGFBP-3, r = -0.37 and P = 0.005). Free IGF-I was inversely related to fasting glucose in IDDM subjects (r = -0.35; P = 0.01), whereas the relationship between total IGF-I and fasting glucose did not reach significance (r = -0.27; P = 0.06). Age-adjusted free IGF-I levels were significantly higher (P < 0.05) in IDDM subjects with retinopathy than in subjects without retinopathy after adjustment for age. Total IGF-I and IGFBP-3 levels were positively related to GFR (total IGF-I, r = 0.35 and P < 0.05; IGFBP-3, r = 0.28 and P < 0.05). Both of these differences lost significance after adjustment for age. Free IGF-I, total IGF-I, and IGFBP-3 levels were lower and IGFBP-1 levels were higher in insulin-treated IDDM subjects compared to those in age- and sex-matched controls. Free IGF-I, total IGF-I, and IGFBP-3 levels decreased significantly with age in IDDM subjects. Age-adjusted free IGF-I levels in subjects with diabetic retinopathy were higher than those in subjects without diabetic retinopathy. Total IGF-I and IGFBP-3 levels were positively related to GFR in IDDM subjects, but these relations were lost after adjustment for age. Measurement of serum free IGF-I levels in IDDM subjects did not have clear advantages compared to that of total IGF-I, IGFBP-1, and IGFBP-3 levels. Serum IGF-I and IGFBPs reflect their tissue concentrations to a various degree. Consequently, extrapolations concerning the pathogenetic role of the IGF/IGFBP system in the development of diabetic complications at the tissue level remain speculative.

Adolescent↗

Acromegaly: the significance of serum total and free IGF-I and IGF-binding protein-3 in diagnosis.

We have studied the physiological and clinical relevance of measurements of serum total and free IGF-I and IGF-binding protein-3 (IGFBP-3) in 57 previously untreated patients with active acromegaly (32 males, 25 females; mean age 47 years) as compared with sex- and age-matched normal healthy controls. Serum total and free IGF-I, but not IGFBP-3, are suitable biochemical parameters for screening for acromegaly. In acromegalics, the mean 24 h serum GH, total IGF-I and IGFBP-3 levels tend to decrease with age. However, in our series of patients, mean 24 h serum GH levels, IGFBP-3, total and free IGF-I do not correlate with disease activity in acromegaly.

Acromegaly↗

IGFBP-3 is a poor parameter for assessment of clinical activity in acromegaly.

OBJECTIVE: Elevated serum IGF-I and IGF binding protein-3 (IGFBP-3) levels have been found in patients with active acromegaly. We have studied the relative diagnostic merits of measurements of IGFBP-3 compared with IGF-I as a parameter of disease activity in these patients. DESIGN/PATIENTS: Thirty untreated patients with acromegaly were compared with 30 healthy adults. MEASUREMENTS: Twenty-four-hour sampling for serum GH in patients with acromegaly, serum IGF-I and IGFBP-3. RESULTS: Mean IGF-I levels were 22.0 nmol/l (range 6.5-38.4) in the healthy adults and 118.7 nmol/l (range 67.7-206.0) in patients with acromegaly. Mean IGFBP-3 levels were 3.5 mg/l (range 2.1-4.8) in controls and 5.4 mg/l (range 4.2-6.6) in patients with acromegaly. Mean IGF-I/IGFBP-3 ratios were 6.5 nmol/mg (range 1.9-14.5) in the healthy adults and 22.0 nmol/mg (range 14.3-32.7) in patients with acromegaly. There was a considerable overlap for IGFBP-3 levels but not for IGF-I levels, between normals and acromegalics. The IGF-I/IGFBP-3 ratio also showed overlap between normals and acromegalics. There was a significant correlation between the mean 24-hour GH and IGFBP-3 levels (P = 0.036) and between the IGF-I and IGFBP-3 levels (P < 0.002) in acromegaly. In patients with acromegaly, the IGFBP-3 levels showed a decrement, but the IGF-I/IGFBP-3 ratio did not change significantly with age. CONCLUSIONS: IGFBP-2 has no additional discriminatory value over IGF-1 measurements for the assessment of clinical activity in acromegaly. In acromegaly, IGFBP-3 decreases with increasing age. In acromegaly, IGFBP-3 levels significantly correlate with mean 24-hour GH levels and IGF-I levels.

Acromegaly↗

Hemodynamic and biochemical effects of the AT1 receptor antagonist irbesartan in hypertension.

We studied the hemodynamic, neurohumoral, and biochemical effects of the novel angiotensin type 1 (AT1) receptor antagonist irbesartan in 86 untreated patients with essential hypertension on a normal sodium diet. According to a double-blind parallel group trial, patients were randomized to a once-daily oral dose of the AT1 receptor antagonist (1, 25, or 100 mg) or placebo after a placebo run-in period of 3 weeks. Randomization medication was given for 1 week. Compared with placebo, 24-hour ambulatory blood pressure did not change with the 1-mg dose, and it fell (mean and 95% confidence interval) by 7.0 (4.2-9.8)/6.1 (3.9-8.1) mm Hg with the 25-mg dose and by 12.1 (8.1-16.2)/7.2 (4.9-9.4) mm Hg with the 100-mg dose. Heart rate did not change during either dose. With the 25-mg dose, the antihypertensive effect was attenuated during the second half of the recording, and with the 100-mg dose, it was maintained for 24 hours. Baseline values of renin and the antihypertensive response to the 25- and 100-mg doses were well correlated (r = .68, P < .01). Renin did not change with the 1-mg dose, but it rose threefold to fourfold with the 25-mg dose and fourfold to fivefold with the 100-mg dose 4 to 6 hours after administration. With the 100-mg dose, renin was still elevated twofold 24 hours after dosing. The changes in renin induced by the AT1 receptor antagonist were associated with parallel increments in angiotensin I and angiotensin II. Aldosterone, despite AT1 receptor blockade, did not fall.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Comparison of sublethal and lethal criteria for nine different chemicals in standardized toxicity tests using the earthworm Eisenia andrei.

In this study, the effects of nine different chemicals on the survival, growth, and reproduction of the earthworm species Eisenia andrei were determined using a recently developed method. Earthworms were exposed for 3 weeks to the test chemicals in an artificial soil substrate. Additional data on the acute toxicity of these chemicals were derived from the literature. For some chemicals, cocoon production was the most sensitive parameter (cadmium, chromium, paraquat, fentin, benomyl, phenmedipham), while for others cocoon hatchability was most sensitive (pentachlorophenol, parathion, carbendazim). In the case of parathion, growth of the worms seemed to be even more sensitive than reproduction. As an overall parameter for the effect on earthworm reproduction, the total number of juveniles produced per worm appeared to be a useful parameter. Differences between (acute) LC50 values and the lowest NOEC value for effects on growth and reproduction were different for each chemical. Difference was greatest for cadmium (a factor of greater than 100) and smallest for fentin, benomyl, and pentachlorophenol (a factor of 5-6).

Animals↗

Plasma prorenin as an early marker of microvascular disease in patients with diabetes mellitus.

To test the hypothesis that a high plasma prorenin can be used as an early marker of microvascular complications in patients with diabetes mellitus plasma prorenin was measured in 44 patients with urinary albumin excretion between 30 and 300 mg/24 h (microalbuminuria) and 120 patients with urinary albumin excretion below 30 mg/24 h (normoalbuminuria). A high plasma prorenin was associated with diabetic retinopathy, particularly the proliferative type, serum creatinine and the 24 h urinary albumin excretion rate. Plasma prorenin was not correlated with age, duration of diabetes, glycosylated hemoglobin, blood glucose, and blood pressure. The association between elevated plasma prorenin and retinopathy remained significant after adjustment for serum creatinine and albumin excretion. Independent of the presence or absence of microalbuminuria, the mean plasma level of prorenin was not above normal in patients without retinopathy and was 2 to 3 times normal in patients with proliferative retinopathy. Thus retinopathy appears to be an important determinant of abnormally high plasma prorenin. Angiotensin converting enzyme (ACE) was elevated in the patients with diabetes mellitus as compared to control subjects but the plasma levels of ACE in diabetics with normoalbuminuria was not significantly different from the group with microalbuminuria. Plasma prorenin was not associated with ACE. A plasma level of prorenin of 225 mU/L had a sensitivity of 0.84 and a specificity of 0.82 for detecting the presence of microalbuminuria.

Adult↗

Bronchial asthma improved after removal of a phaeochromocytoma.

It is uncommon for bronchial asthma to be a symptom of phaeochromocytoma. We describe a patient with a phaeochromocytoma who presented with worsening of her asthma and persistent dyspnoea between attacks. She had markedly elevated levels of catecholamines. After surgical resection of the phaeochromocytoma there was a lasting improvement of the bronchial asthma. We hypothesize that worsening of bronchial asthma in phaeochromocytoma patients may be due to catecholamine-induced deterioration of asthma.

Adrenal Gland Neoplasms↗

[Hypercalcemia in sarcoidosis].

In a 56-year-old man hypercalcaemia and kidney function impairment were the presenting symptoms of sarcoidosis. The diagnosis was supported by the finding of elevated 1,25-dihydroxyvitamin D levels and of a cluster of epithelioid macrophages in aspirated bone marrow. By exclusion of other granulomatous diseases and a favourable reaction of the hypercalcaemia and renal function to treatment with prednisone the diagnosis was confirmed. The relationship between the autonomous extrarenal production of 1,25-dihydroxyvitamin D and the hypercalcaemia is discussed.

Calcitriol↗

[The effect of immunoscintigraphy with monoclonal antibodies on assays of hormones and tumor markers. This is not the end of the matter!].

The use of monoclonal antibodies in medicine for in-vivo diagnostic methods and for therapeutic purposes will increase in the future. Although monoclonal antibodies possess a high specificity, the animal origin of these antibodies remains a problem. Repeated administration of animal monoclonal antibodies (in vivo) may induce the formation of human antibodies against these monoclonal antibodies. Because animal monoclonal antibodies are also used in laboratory assays (in vitro), the presence of human antibodies against these animal monoclonal antibodies may cause spuriously elevated or depressed results of these assays. The clinician should be alert to this possibility. A case history is presented to demonstrate the problem.

Aged↗

Study of the molecular mechanism of decreased liver synthesis of albumin in inflammation.

Hypoalbuminemia in inflammatory disorders is not an infrequent finding. However, little is known about albumin synthesis in these patients. In the present study we have measured the albumin synthesis in four patients with inflammatory diseases using the [14C]carbonate technique. Because inflammation causes a decreased albumin synthesis and this decreased synthesis could not be related to a reduced amino acid supply, we have also examined the possible molecular mechanisms of reduced albumin synthesis during inflammation using in vivo and in vitro experiments in rats. In rats with turpentine-induced inflammation, serum albumin concentration and liver albumin mRNa level were markedly decreased. These changes could not be reproduced by administration of fibrinogen-, or fibrin-degradation products, or several hormones, such as corticosteroids, growth hormone, and adrenaline. However, monocytic products, especially interleukin 1, postulated to be important mediators of the inflammatory response, reduced albumin synthesis and liver albumin messenger RNA content but not total protein synthesis in rats in vivo and in primary cultures of rat hepatocytes. These findings suggest that monocytic products play an important role in reduced albumin synthesis during inflammation.

Adult↗

Politics of AIDS.

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Acquired Immunodeficiency Syndrome↗