Biomedical subjects
Publications and source records attributed to G Heynen.
Amlodipine is a new calcium antagonist of the 1.4-dihydropyridine group for treatment of hypertension and angina pectoris. Amlodipine is distinct from other calcium antagonists by its pharmacokinetic profile: slower onset of action with less acute vasodilatation associated side effects and a sustained antihypertensive and anti-anginal efficacy over 24 hours.
The sensitivity of peripheral tissues to insulin is of pathophysiological, therapeutic and possibly also of prognostic relevance. Calcium channel blockers are widely used in the treatment of cardiovascular disorders that are commonly associated with decreased insulin sensitivity (SI). To evaluate the effects of calcium channel blokkade on SI, glucose homoeostasis and lipid profiles, studies were made of SI (determined by the Minimal Model Method of Bergman), basal glucose and insulin levels, serum total triglyceride (Tg) and lipoprotein cholesterol (C) fractions and certain other variables in 38 healthy young men (24 y) during placebo and after 3 weeks of calcium channel blockade with amlodipine 5 mg once daily. Measurements were made after 3 days on a standard diet (2200 kcal.day-1, 45% carbohydrates, 40% fat and 15% proteins) and after an overnight fast. Compared to placebo, amlodipine decreased supine systolic blood pressure (P less than 0.01). Heart rate, body weight and 24 h urinary sodium excretion were unaltered, and so were fasting plasma glucose (placebo vs amlodipine: 4.86 vs 4.83 mmol.l-1, respectively) and insulin levels (7.7 vs 7.9 microU.ml-1), SI (10.5 vs 9.6.10(-4) x min-1 pro microU.ml-1), serum total Tg, C and lipoprotein C fractions. The findings demonstrate unchanged insulin sensitivity and secretion, as well as lipoprotein regulation, during maintenance administration of 5 mg amlodipine daily to healthy young men.
PURPOSE: Essential hypertension is, in some patients, complicated by impairment of insulin-mediated glucose disposal and hyperinsulinemia. Whether this metabolic disturbance is a consequence of the hypertensive process or whether it may precede, and thus possibly promote, the development of hypertension has been unknown. SUBJECTS AND METHODS: Searching for hereditary or familial defects in hypertension-prone humans, we prospectively investigated insulin sensitivity, plasma insulin and glucose, and serum lipoproteins in normotensive offspring of essential hypertensive as compared with age- and body habitus-matched offspring of normotensive families. RESULTS: Compared with 78 control subjects, 70 offspring of essential hypertensive parents had similar age (mean +/- SEM: 24 +/- 1 versus 24 +/- 1 years, respectively) and body mass index (22.3 +/- 0.2 versus 22.4 +/- 0.2 kg/m2), a blood pressure of 127/77 +/- 1/1 versus 123/76 +/- 1/1 mm Hg (p less than 0.05 for systolic), and significantly elevated (p less than 0.01 to 0.001) fasting plasma insulin levels (9.9 +/- 0.3 versus 8.6 +/- 0.3 microU/mL), serum total triglycerides (1.03 +/- 0.06 versus 0.83 +/- 0.03 mmol/L), total cholesterol (4.37 +/- 0.08 versus 3.93 +/- 0.07 mmol/L), low-density lipoprotein cholesterol (2.45 +/- 0.08 versus 2.14 +/- 0.07 mmol/L), and total/high-density lipoprotein cholesterol ratio (4.3 +/- 0.1 versus 3.7 +/- 0.1). Insulin sensitivity was lower (9.4 +/- 0.7 versus 13.2 +/- 1.1 x 10(-4) x minute-1/microU/mL, p less than 0.001), while post-glucose-load plasma insulin levels were higher (p less than 0.05) in the 41 offspring of essential hypertensive parents than in the 38 offspring of normotensive parents so investigated. CONCLUSION: These findings demonstrate that young normotensive humans in apparently excellent health but with one essential hypertensive parent tend to have an impairment of insulin-mediated glucose disposal, hyperinsulinemia, and dyslipidemia. It follows that a familial trait for essential hypertension seems to coexist commonly with defects in carbohydrate and lipoprotein metabolism that can be detected before or at least at a very early stage of the development of high blood pressure as judged by resting blood pressure measurements.
Revision of failed cemented total hip arthroplasties represents a major technical challenge to orthopaedic surgeons. One of the problems encountered is loss of femoral bone stock, making restoration of prosthetic stability difficult. Revision with uncemented components may allow healing of bone defects.
Proteoglycan metabolism was investigated in longterm tissue cultured human cartilage. Visually intact cartilage from adult donors showed improving accumulation rates for 35sulfate labelled proteoglycans over a 6-week period. The loss of newly synthesized molecules in the nutrient culture media was low and constant. Fibrillated cartilage from a 17-year-old male showed higher basal 35S incorporation rates and the proportions of 35S proteoglycan aggregates were higher than in normal tissue. These observations may reflect the immature status of the tissue or an attempt at repair. However samples lost increasing amounts of 35S proteoglycans in the incubation media. This material appeared to be monomeric proteoglycan. The amount of 35S activity retained in the fibrillated tissue matrix fell during culture as did the proportion of proteoglycan aggregates. Thus catabolic events were postulated in these fibrillated cartilage samples. When piroxicam was added to the incubation media more newly synthesized proteoglycans were retained in the intercellular matrix of the fibrillated samples. Increased accumulation of 35S activity was seen in some of the batches of visually intact cartilage.
Twenty healthy males were randomly divided into three groups. Each subject received either 405 mg elemental calcium (Ca) as a salt linked to an amino acid precursor, 405 mg CaC12 or 1000 mg Ca as Ca gluconolactate and carbonate. In all three cases, Ca intake led to an increase of serum Ca and TCT production and a decrease of PTH liberation. However, when Ca is linked to the amino acid precursor, an elective stimulation of growth hormone (GH) and somatomedin C (SmC) occurs. Due to the nature of its amino acid precursor, this salt seems to stimulate GH and SmC liberation through hypophysis. This could be a major pathway in decoupling of the sequence resorption-formation and therapy of metabolic bone diseases.
The purpose of this review is to define the toleration profile of piroxicam through the clinical experience gathered in 109,495 patients and to estimate how it compares with that of other commonly prescribed non-steroidal anti-inflammatory drugs (NSAIDs) in 37 comparative clinical trials involving 3,580 patients. The estimated total exposure to piroxicam in clinical trials reported here is approximately 2.6 million patient days. The toleration profile of piroxicam is typical of an inhibitor of prostaglandins, with a relatively low reported incidence of adverse events necessitating discontinuation of therapy. Pharmacokinetics are not age- or sex-dependent, and - with the exception of oedema - the incidence of adverse events does not increase with age. Piroxicam exhibits better toleration than indomethacin (75 to 150 mg daily), naproxen (1,000 mg daily), and enteric coated acetylsalicylic acid (3.5 to 5 g daily), and is as well tolerated as diclofenac (75 to 150 mg daily), naproxen (500 to 750 mg daily), and ibuprofen (2.4 g daily). Piroxicam has the advantage that once-daily dosage is sufficient to provide efficacy equal to or better than these comparative agents.
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18 patients with Paget's disease were treated orally with (3-amino-1-hydroxypropylidene)-1, 1-bisphosphonate (A.P.D.). In most cases bone resorption became normal within a week of treatment, whereas the return to normal bone formation took 3-6 months; this difference produced a transient imbalance between resorption and formation. In biopsy specimens taken during treatment the numbers of osteoclasts and osteoblasts decreased towards normal and excess osteoid disappeared.
Whisky (25-50 ml) increased plasma levels of immunoreactive calcitonin (iCT) in seventeen of nineteen patients with chronic renal failure. The effect was greater in patients with high levels of iCT than in those with normal levels. Changes in plasma iCT were not related to changes in calcium, phosphate or immunoreactive gastrin, but were inhibited by the prior administration of propranolol.
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Thirty-three out-patients with rheumatoid arthritis completed the study intended to compare under double-blind conditions, 50 mg levamisole tablets with placebo. Patients were given the double-blind medication at a dosage of one tablet t.i.d. for 3 months, and at a dosage of one tablet t.i.d., on 2 consecutive days every week for the next 3 months. Pain score, duration of morning stiffness, articular index and E. S. R. were recorded at the start of treatment, after 3 months of treatment and at the end of treatment. The levamisole patients made significantly better progress than did the placebo patients: for E.S.R. after 3 months of treatment, and for E.S.R., pain and morning stiffness by the end of treatment. Ten levamisole patients and 5 placebo patients reported adverse reactions. These were mainly gastrointestinal symptoms in the levamisole-treated patients.
Following the discovery that the kidney is involved in the metabolism of vitamin D, a causal relationship has been sought between defective production of 1,25-dihydroxy vitamin D3 and bone disease in chronic renal failure. This paper reviews some of the clinical evidence for and against such a relationship, and considers the possible role of other vitamin D metabolites in the pathophysiology of renal bone disease.
Two children suffering from renal osteodystrophy were treated by 1 alpha hydroxycholecalciferol (1 alpha OHD3) 1 microgr. each day, for 18 months. In both the level alkaline phosphatase decreased at the same time as endogenous immunoreactive CT increased, iPTH did not change steadily, whereas plasma creatinine rise. As plasma calcium concentration did not increase, it is suggested that the increase in endogenous CT concentration is a part of the favourable response to the treatment by 1 alpha OHD3.
The administration of 1 alpha hydroxycholecalciferol (1 alpha OHD3) (2 microgr. per day) increase the plasma immunoreactive calcitonin (i CT) concentration in normal subjects after six days. This effect is also observed in patients suffering from Paget's disease of bone, suggesting that the mechanism responsable for the secretion of CT following the administration of 1 alpha is not disturbed in that disease. By contrast, the absence of increase in plasma iCT in the patients suffering from chronic renal failure suggests an impaired secretion of CT in that disorder.
Forty patients with severe bone disease and chronic renal failure were treated with 1 alpha-hydroxycholecalciferol (1 alpha-OHD3) or 1,25-dihydroxycholecalciferol (1,25(OH)2D3) for 7--49 months (total = 738 patient months). There were symptomatic, biochemical and radiographic improvements in the majority of patients (greater than 70 per cent). Paired bone biopsies, taken before and during treatment in 26 patients, showed no change in bone matrix area, whereas matrix area decreased in a control group of 26 patients over the same period. There were small but consistent decreases in bone marrow fibrosis and in bone cell (osteoblast and osteoclast) counts in treated patients but not in controls. However, the proportion of patients who showed histological 'cure', in the sense of complete reversal of marrow fibrosis or excess osteoid was no greater in the treated than in the control group...
Small doses (1-10 microgram daily) of 24,25-dihydroxycholecalciferol (24,25-(OH)2D3), a renal metabolite of vitamin D of uncertain function, increased intestinal absorption of calcium in normal people and in patients with various disorders or mineral metabolism, including anephric subjects. In five of six patients studied, calcium balance increased, but, unlike 1,25-dihydroxycholecalciferol, 24,25-(OH)2D3 did not increase plasma or urinary calcium concentrations. These results suggest that 24,25-(OH)2D3 may be an important regulator of skeletal metabolism in man with potential value as a therapeutic agent.