Effects of standard oral glucose loading on the renin-angiotensin-aldosterone system and its relationship to circulating insulin.
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Biomedical subjects
Publications and source records attributed to J Flammer.
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In a retrospective study of 114 patients under treatment for chronic glaucoma (81 without and 33 with visual field defect) over an 11-year period of observation, a highly significant correlation between intraocular pressure and progression of visual field defects could be demonstrated. This correlation could be shown for the visual field outer boundary in 81 eyes with ocular hypertension and for typical visual field defects in 33 eyes with chronic glaucoma. The relationship was, however, only significant when both the standard deviation of the annual intraocular pressure and the influence of cataract development upon visual acuity were considered. Quantitative analysis of the results of Goldmann perimetry was by planimetry and took into account only changes during the 11-year observation period.
In a double-blind study, a significant blockade of the beta-adrenergic system was verified on 20 healthy volunteers after instillation of 4 drops of Timolol maleate 0.5% daily. The systemic blocking effect is obvious after stimulation of the sympathetic system by physical activity. Under these conditions the blood pressure and the heart rate of volunteers treated with Timolol rise less than those of volunteers given a placebo. A theoretical explanation is given and possible clinical implications are discussed.
A study was carried out by seven ophthalmologists practising in the Berne region on 473 patients complaining of eye strain. Medical histories were taken by questionnaire, refraction was done and phoria measured, followed by therapy in accordance with the physician's opinion. In 380 cases, glasses were prescribed, including prismatic glasses for 14 patients. In 123 cases, local medical therapy was instituted. The statistica evaluation of pre-treatment findings and results of therapy, was carried out using a computer. The principial complaints before treatment were eyestrain and visual disturbances, followed by conjunctival irritation and headache. Women complained more about headaches, men more about visual disturbances. A majority of the patients with visual disturbances needed minus lenses, while for the treatment of headaches mostly plus lenses were needed. In patients with conjunctival irritation local medical treatment resulted in additional relief of symptoms. Cylindric correction had only a minor influence on the result of therapy. Heterophoric patients did not have more complaints than orthophoric ones, and results with spectacles without prisms were the same as in orthophoric patients.
Quantitative assessment of signs or symptoms of neuropathy, and the beat-to-beat variation, valsalva, orthostasis, handgrip and cold pressor tests, and measurements of plasma renin and catecholamine excretion rate were performed in 23 diabetic patients and 10 age-matched normal subjects. Significant inverse correlations were found between the clinical score and the beat-to-beat variation (a test of efferent vagus function) (r=-0.55, -0.72, P less than 0.0005) or the pressor response to handgrip (possible test of efferent sympathetic integrity (r=p less than 0.005) or the values of both tests combined (r=-0.79, P less than 0.0005); but not with the other measured parameters. Beat-to-beat variation was abnormal in all 9 diabetics with increased and in 9 of 14 with normal clinical score, whereas only seven and one patient from these subgroups, respectively, had an abnormal Valsalva ratio. The pressor response to handgrip was only slightly reduced in the diabetic patients, with greater tendency in those with abnormal clinical score. Additional possible indices of adrenergic dysfunction such as the pressor response to cold stimulus, plasma renin levels and noradrenaline or adrenaline excretion rates did not differ significantly between normal subjects and diabetics. These finding demonstrate a greater prevalence of parasympathetic as compared to sympathetic impairment in diabetic autonomic neuropathy; the beat-to-beat variation was the most sensitive among the tests used. An assessment of clinical evidence combined with non-invasive functional procedures such as the beat-to-beat variation and handgrip tests provide a valuable and easy to perform tool in the evaluation of diabetic neuropathy.
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The pathogenic role of the sympathetic system in essential hypertension was evaluated by combined analysis of plasma catecholamine levels and the pressor sensitivity to endogenous norepinephrine. The latter was estimated indirectly by the ratio between changes in blood pressure and those in plasma norepinephrine after adrenergic neuronal blockage with debrisoquine (given orally for 6 weeks). Normal subjects and patients with borderline or established essential hypertension had comparable pretreatment levels of plasma norepinephrine and epinephrine. Debrisoquine lowered plasma norepinephrine by a similar degree (almost 50%) in these three groups; in contrast, blood pressure decreased only slightly in normal or borderline hypertensive subjects [-3.4 +/- 3.2% and -5.4 +/- 1.6% (SE), respectively] but fell significantly more (P less than 0.005) in patients with established essential hypertension (-20.7 +/- 3.9%). The ratio between percentile changes in blood pressure and those in endogenous norepinephrine levels was comparable in normal and borderline hypertensive subjects (0.03 +/- 0.08 and 0.17 +/- 0.04, respectively), but increased (P less than 0.001) in established essential hypertension (0.62 +/- 0.11). This suggests that essential hypertension may be maintained, at least partly, by the inappropriate association of normal plasma norepinephrine levels with increased norepinephrine pressor sensitivity.
The pathogenic role of the sympathetic system in essential hypertension was evaluated by combined analysis of urinary and plasma catecholamine levels and pressor sensitivity to endogenous noradrenaline. The latter was estimated indirectly by the ratio between percentile changes in blood pressure and plasma noradrenaline following adrenergic neuronal blockade with the agent debrisoquine. In normal and mildly hypertensive (141/91 to 160/105 mm Hg) subjects, supine or upright plasma levels and excretion rates of noradrenaline correlated (p less than 0.01) with age and were comparable; no correlation was present in patients with moderate to severe hypertension (greater than 160/105 mm Hg) who tended to have supernormal noradrenaline levels under the age of 40 years. Adrenaline values were normal in essential hypertension. Pressor sensitivity to noradrenaline was comparable in normal and mildly hypertensive subjects (0.03 +/- 0.08 [SE] and 0.17 +/- 0.04, respectively) but increased (p less than 0.001) in moderate to severe hypertension (0.62 +/- 0.11). These findings suggest that moderate to severe essential hypertension may be maintained, at least partly, by the inappropriate association of normal plasma noradrenaline levels with increased noradrenaline pressor sensitivity. This may also provide a rational basis for the use of pharmacologic adrenergic inhibition in the treatment of moderate to severe essential hypertension.
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1. The effect of diuretic therapy on serum lipids and lipoprotein fractions was evaluated in 16 normal or labile hypertensive subjects who received in cross-over fashion chlorthalidone, frusemide or mefruside, each for 4 weeks (group A); and in 13 patients with essential hypertension treated with chlorthalidone for 6 weeks (group B). 2. All three diuretics significantly increased the ratio between serum beta- and alpha-lipoprotein fractions. This was due to an increase of the serum beta-lipoprotein fraction while the alpha-lipoprotein fraction was not changed significantly (group A) or decreased (group B). Serum cholesterol or triglycerides tended to be increased, but mean changes were often not significant. 3. The observed alterations in serum lipoproteins are consistent with the possibility of an increased risk for coronary heart disease which could offset partly the beneficial effects of a lowered blood pressure in diuretic-treated patients with hypertension.
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In a 52-year-old patient with Bartter's syndrome, peripheral venous prostaglandin E2 (PGE2) and plasma renin activity (PRA) levels were markedly elevated and plasma aldosterone concentration (pa) was at the upper limit of normal, though inappropriately high relative to the decreased plasma and whole body potassium levels. Blood pressure, plasma volume, exchangeable body sodium, plasma cortisol and urinary catecholamines were normal. Renal venous PGE2 was two to three times higher than peripheral PGE2. Indomethacin (300 mg/day) decreased peripheral PGE2 by 50%, PRA by 84% and PA by 72%, induced a positive potassium balance (greater than 350 mEq) with normal plasma potassium levels, and returned the previously marked resistance to the pressor effect of angiotensin II to normal. During the entire study, highly significant correlations (p less than 0.001) between peripheral PGE2 and PRA (r = 0.86) or PA (r = 0.90) were found. In this patient the hyperreninemia was not related to volume depletion. These data indicate that in Bartter's syndrome renal PGE2 secretion may be increased, systemic blood levels of PGE2 may be elevated and closely related to PRA, and indomethacin ameliorates these abnormalities and improves potassium balance. These results are consistent with the ascription of an important role to excessive renal PGE2 secretion in the pathogenesis of Bartter's syndrome.
Interrelations among plasma renin activity (PRA), aldosterone and cortisole levels, 0lood volume, exchangeable sodium, urinary catecholamines, and blood pressure were studied in 35 normal subjects and 60 age-matched non-azotemic patients with diabetes mellitus (60% with hypertension, 15% with orthostatic hypotension). Basal PRA, plasma aldosterone, cortisol, blood volume, plasma potassium, and urinary electrolytes were comparable in diabetic and normal subjects. Diabetic patients, however, had a 10% increase in body sodium (P less than 0.01), and 8% of them showed normal postural PRA responses and subnormal aldosterone responses; 22% had subnormal PRA and normal aldosterone responses, and 17% had subnormal responses of PRA and aldosterone. Non-PRA-related aldosterone responses could not be explained by ACTH or electrolytes. Orthostatic decreases in blood pressure correlated (P less than 0.01) with both catecholamine excretion and basal PRA. This suggests that in diabetes mellitus, body sodium is increased. Basal PRA and plasma aldosterone are usually normal, but their postural responses are frequently impaired. Absent aldosterone responses, despite normal PRA responsiveness, may reflect an adrenal abnormality or an ineffective form of renin. Marked postural aldosterone stimulation, unrelated to PRA, ACTH, or electrolytes, points to a potent unknown factor in aldosterone control. Low levels of free peripheral catecholamines and PRA may be complementary factors contributing to postural hypotension.
Dipyridamole is known to inhibit platelet aggregation and to induce vasodilatation. It has been shown that dipyridamole increases blood flow in various tissues in humans as well as in the eyes of animals. We studied the influence of dipyridamole in a prospective open trial in 23 patients with impaired ocular circulation due to different causes, based on experienced clinical judgement, such as anterior ischemic optic neuropathy, vasospastic syndrome, glaucoma, or central retinal vein occlusion. Blood flow velocities in the ophthalmic artery, central retinal artery and vein, one lateral and one medical posterior ciliary artery were measured using a Siemens Quantum 2000 color Doppler device. Blood flow velocities were measured before and under treatment. Dipyridamole increased blood flow velocities significantly in all vessels measured. Therefore, it seems promising to evaluate the effect of dipyridamole over a longer period in patients with impaired ocular blood flow.
The endothelium influences local vascular tone by releasing endothelium-derived relaxing factors such as nitric oxide, prostacyclin and a putative hyperpolarizing factor. In isolated ophthalmic arteries and the perfused eye, all endothelial factors importantly contribute to vascular regulation. In larger ophthalmic vessels, this is due to their effects on vascular smooth muscle cells; in smaller vessels, pericytes can be influenced as well. Contracting factors formed include peptide endothelin-1 and cyclooxygenase products, such as thromboxane A2 and prostaglandin H2. In the peripheral circulation endothelial dysfunction occurs under pathological conditions, both in conduit arteries and the microcirculation. An imbalance of endothelium-derived relaxing and contracting factors could be important for the development of vascular ophthalmic complications like hypertension, diabetes, arteriolosclerosis and retinal ischemia. Endothelial dysfunction may also contribute to vasospastic events in retinal migraine and some forms of low tension glaucoma associated with Raynaud phenomenon and migraine.
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PURPOSE: To assess sex difference and parameters possibly accounting for such a difference in healthy subjects evaluated by means of the Langham Ocular Blood Flow (OBF) System. METHODS: Pulse amplitude of intraocular pressure (IOP) and pulsatile ocular blood flow (POBF) as measured with the Langham OBF System were assessed in 86 healthy men and 69 healthy women. RESULTS: Compared to men, women showed higher POBF (mean +/- SD: 722.6 +/- 152.8 versus 647.8 +/- 164.9 microL/min; P =.0056) and pulse amplitude (mean +/- SD: 2.3 +/- 0.7 versus 2.0 +/- 0.6 mm Hg; P =.0043) values. Sex difference was still significant after correcting for age, refraction, blood pressure, IOP, and pulse rate. Pulse amplitude correlated negatively with pulse rate, and POBF correlated negatively with IOP. Women had higher readings in pulse amplitude and POBF, even after correcting for age, refraction, IOP, blood pressure, and pulse rate. CONCLUSIONS: While using the Langham OBF System, one needs to be aware of sex difference that is independent of other hemodynamic parameters. How the observed difference in POBF is related to ocular blood flow, and how it might influence the preponderance of various ocular diseases in men or women remains to be clarified.
PURPOSE: Many physiological parameters, including blood pressure, show circadian variations. Diurnal fluctuations of the optic nerve head (ONH) circulation have not yet been studied. The purpose of the present study was to determine the pattern of ONH blood flow variations over a 24-hour period in healthy subjects. METHODS: The subject group comprised 15 healthy volunteers (6 women, 9 men) aged 22 to 43 years (mean +/- SEM: 28.2 +/- 1.3 years). Blood flow in the ONH was measured by laser Doppler flowmetry (LDF) over a 24-hour period at 08:00, 12:00, 16:00, 20:00, 24:00 hours, and at 08:00 hours the following morning. RESULTS: ONH perfusion varied significantly over time. The mean LDF-flow during daytime ranged from 8.2 to 8.9 arbitrary units (AU) and fell at midnight to 7.1 AU (P =.0015). The mean LDF-volume during daytime was 0.23 to 0.24 AU and decreased at midnight to 0.20 AU (P =.04). The mean LDF-velocity ranged from 0.39 to 0.41 kHz with no significant differences at any time point. CONCLUSIONS: Our study in normal subjects reveals small mean changes of ONH perfusion during daytime and a significant reduction at night. The physiological and clinical relevance of the nocturnal dip in the ONH perfusion needs to be determined in future studies.