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Biomedical subjects

J Giese

Publications and source records attributed to J Giese.

At least 19 recordsLinked to original sources

Renal sites of action of physiological increases in plasma atrial natriuretic factor concentration in essential hypertension.

OBJECTIVES: To investigate the renal, haemodynamic and neurohormonal responses to low-dose infusions of atrial natriuretic factor (ANF) in hypertensive humans. DESIGN: Ten patients with mild-to-moderate essential hypertension received incremental infusions of 3 and 6 ng/kg per min ANF or vehicle alone whilst on a constant dietary sodium intake. A 90-min basal clearance period was followed by two 2-h infusion periods, with urine collection in the last 90 min of each period. In each of the three clearance periods, glomerular filtration rate (GFR), renal tubular function, and the activity of the renin-angiotensin and sympathetic nervous systems were determined. METHODS: The renal sites of ANF action were established by simultaneous measurements of 51Cr-ethylenediaminetetraacetate lithium and sodium clearances. Plasma concentrations of neurohormones were measured by radioimmunoassays. RESULTS: Plasma ANF concentrations increased by 1.6- and 2.5-fold during the lower and higher ANF infusion rates, respectively. Plasma cyclic guanosine monophosphate concentrations increased in parallel. ANF caused no changes in supine systolic and diastolic blood pressure or in heart rate. In contrast, haematocrit values increased progressively across the study. The renal effects of ANF administration were characterized by an unaltered GFR and significant increases in the renal clearances of lithium (a marker of end-proximal fluid delivery) and sodium when compared with vehicle infusions, whereas urine flow did not change. Estimated values of fractional proximal and distal tubular sodium reabsorption decreased significantly. Plasma concentration of active renin decreased during ANF infusions, but no significant changes in plasma levels of renin substrate, angiotensin I, angiotensin II or aldosterone were observed. A subtle activation of the sympathetic nervous system was indicated by a moderate increase in plasma noradrenaline during the ANF infusions. CONCLUSIONS: These results indicate that even small increases in plasma ANF, as can be found during physiological conditions, induce natriuresis in patients with essential hypertension by enhancing fluid delivery from the proximal tubules, in addition to impairing distal fractional sodium reabsorption. With minor exceptions, the ANF infusions caused qualitatively and quantitatively similar renal, haemodynamic and endocrine effects in the hypertensive patients as in a previously studied group of normotensive subjects.

Adult

Radioimmunoassay of endothelin in human plasma.

A specific and sensitive radioimmunoassay (RIA) for determination of endothelin-1 (ET-1) in human plasma has been developed. Antibodies were raised in rabbits using synthetic ET-1 conjugated to thyroglobulin as immunogen. The antibodies obtained were used at a final dilution of 1:300,000 yielding maximum binding of 61.7 +/- 3.0% (mean +/- 1 SD, n = 20) of 125I-ET-1. The ID50 (inhibitory dose 50%) was 4.5 +/- 0.6 fmol/100 microliters (mean +/- 1 SD, n = 20). The sensitivity of the RIA was 0.33 fmol/100 microliters standard solution. No cross reactivity was observed with endothelin-3, big-endothelin-1, atrial natriuretic factor, angiotensin I or angiotensin II. The cross-reactivity with endothelin-2 was 100%. Endothelin was extracted from acidified plasma with Sep-pak C18 cartridges and recovery of ET-1 added to normal plasma was 70.9 +/- 10.3% (mean +/- 1 SD, n = 12). The concentration of ET-1 in plasma from normal subjects was 1.5 +/- 0.4 pmol/l (mean +/- 1 SD, n = 11) ranging from 1.0 to 2.2 pmol/1. Extracts of normal human plasma subjected to high performance liquid chromatography on a reverse phase C18 column showed one peak of immunoreactivity co-eluting with the standard for ET-1. From these data it is concluded that the immunoreactive material measured in normal plasma with the present RIA is identical to ET-1.

Animals

Efficacy of captopril in postponing nephropathy in normotensive insulin dependent diabetic patients with microalbuminuria.

OBJECTIVE: To assess the effectiveness of angiotensin converting enzyme inhibition in preventing the development of diabetic nephropathy (albuminuria greater than 300 mg/24h). DESIGN: Open randomised controlled study of four years' duration. SETTING: Outpatient diabetic clinic in tertiary referral centre. PATIENTS: 44 normotensive (mean blood pressure 127/78 (SD 12/10) mm Hg) insulin dependent diabetic patients with persistent microalbuminuria (30-300 mg/24h). INTERVENTIONS: The treatment group (n = 21) was initially given captopril (25 mg/24 h). The dose was increased to 100 mg/24 h during the first 16 months and thiazide was added after 30 months. The remaining 23 patients were left untreated. MAIN OUTCOME MEASURES: Albuminuria, kidney function, development of diabetic nephropathy (albuminuria greater than 300 mg/24 h), and arterial blood pressure. RESULTS: Clinical and laboratory variables were comparable at baseline. Urinary excretion of albumin was gradually reduced from 82 (66-106) to 57 (39-85) mg/24 h (geometric mean (95% confidence interval)) in the captopril treated group, whereas an increase from 105(77-153) to 166 (83-323) mg/24 h occurred in the control group (p less than 0.05). Seven of the untreated patients progressed to diabetic nephropathy, whereas none of the captopril treated patients developed clinical overt diabetic nephropathy (p less than 0.05). Systemic blood pressure, glomerular filtration rate, haemoglobin A1c concentration, and urinary excretion of sodium and urea remained practically unchanged in the two groups. CONCLUSIONS: The findings suggest that angiotensin converting enzyme inhibition postpones the development of clinical overt diabetic nephropathy in normotensive insulin dependent diabetic patients with persistent microalbuminuria.

Adolescent

Detailed epidemiological mapping of three onchocerciasis foci in West Africa.

Detailed epidemiological mapping of three isolated foci of hyperendemic blinding onchocerciasis was undertaken in three West African countries as part of community trials of ivermectin, a new microfilaricide for the treatment of human onchocerciasis. The results show that the geographical distribution of the prevalence and intensity of onchocerciasis infection in the community can be very different from what was expected on the basis of demographic and entomological information. The technique of detailed epidemiological mapping is an important tool for the identification of target populations for large scale ivermectin treatment of onchocerciasis. It is being used extensively in the Onchocerciasis Control Programme in West Africa.

Africa, Western

Effects of insulin on renal haemodynamics and sodium handling in normal subjects.

Diabetic patients treated with insulin injected subcutaneously are characterized by peripheral hyperinsulinaemia and an increased mass of total body exchangeable sodium. We hypothesized that this may cause, at least in part, the glomerular hyperfiltration seen in the diabetic state. Six normal subjects were studied on 2 days in random order. Day A: Basal state for 40 min, hyperinsulinaemic euglycaemic clamp for 1 h (insulin infusion rate 2 mU kg-1 min-1 and 50% glucose infusion) and hyperinsulinaemic euglycaemic clamp combined with volume expansion (2 1 isotonic sodium chloride) for 2 h. Day B: as day A, but without insulin and glucose infusion. During combined volume expansion and hyperinsulinaemia an increase in glomerular filtration rate (GFR) (128 +/- 6 vs 117 +/- 8 ml min-1 1.73 m-2, p less than 0.01) and lithium clearance (CLi) (50 +/- 4 vs 33 +/- 5 ml min-1 1.73 m-2, p less than 0.01) was observed compared with basal conditions. GFR and CLi were unchanged during day B. Insulin infusion reduced renal sodium excretion. Absolute proximal tubular reabsorption was unchanged on both days. Insulin infusion without volume expansion caused a decrease of 24% in the fractional distal sodium excretion. Superimposed volume expansion and the concomitant increase in GFR and CLi was accompanied by a subsequent enhanced fractional distal sodium excretion of 27%. The changes in plasma concentrations of aldosterone, renin, angiotensin II, atrial natriuretic peptide and catecholamines did not explain the differences in GFR. An increase in GFR of 10%, comparable with that observed in diabetic patients, was induced by combined hyperinsulinaemia and volume expansion in euglycaemic normal subjects. The enhanced GFR is probably a compensatory response to the sodium retention induced by the action of insulin on the distal tubules.

Adult

Unchanged extraction of atrial natriuretic factor across the chronic ischemic human kidney.

The extractions of atrial natriuretic factor (EANF) and the glomerular filtration marker 51Cr-ethylenediamine tetraacetic acid (EEDTA) were determined before and after intravenous injection of furosemide across each of the two kidneys during renal vein catheterization in hypertensive patients with unilateral or bilateral renovascular disease. Before administration of furosemide, EANF was approximately 55% across both the more and the less affected kidney while EEDTA was significantly decreased across the more affected kidney. Significant lateralization of renin secretion to the more affected kidney was found, demonstrating an enhanced ipsilateral formation of renin. Administration of furosemide caused a significant decrease in EEDTA across the less affected kidney while the ipsilateral EANF did not change. Furosemide caused no change in EEDTA or EANF across the more affected kidney. No significant correlations were found between EANF and EEDTA. These results demonstrate that the extraction of ANF is unchanged across the chronic ischemic human kidney. Furthermore, in the single kidney, changes in EEDTA, as induced by furosemide, are not related to changes in ipsilateral EANF. Since the relation between simultaneously determined single kidney extractions of ANF and 51Cr-EDTA reflects the relation between the single kidney clearance of ANF and the ipsilateral glomerular filtration rate, our data indicate a dissociation between changes in the single kidney glomerular filtration rate and the ipsilateral total renal clearance of ANF.

Atrial Natriuretic Factor

Renal and endocrine effects of physiological variations of atrial natriuretic factor in normal humans.

The renal and endocrine effects of incremental infusions of 3 and 6 ng.kg-1.min-1 of exogenous atrial natriuretic factor (ANF)-(99-126) or placebo were investigated in 10 normal subjects. A 90-min basal period was followed by two 2-h infusion periods with urine collection in the last 90 min of each period. Plasma ANF concentration increased by 50 and 150%, respectively, from a basal value of 6.2 +/- 3.1 pmol/l. Plasma guanosine 3',5'-cyclic monophosphate concentration increased in parallel with ANF. Blood pressure and heart rate were unchanged, whereas hematocrit was stepwise increased. 51Cr-EDTA clearance (GFR) did not change, but ANF caused an increase in Li clearance (a measure of end-proximal fluid delivery), Na clearance, and urine flow compared with time-matched control values. These excretory effects of ANF were mainly due to prevention of the 20- to 50% decreases occurring in the placebo series. Calculated values of fractional proximal and distal tubular Na reabsorption decreased significantly. ANF caused a decrease in plasma concentrations of active renin and aldosterone, whereas renin substrate, angiotensin I, and angiotensin II concentrations were unaltered. A subtle increase in plasma concentrations of norepinephrine and epinephrine was observed during the ANF infusions. These data suggest that the natriuretic effect of ANF is caused by an increased fluid delivery from the proximal tubule in addition to a fall in fractional distal Na reabsorption.

Adult

Comparison of different standards used in radioimmunoassay for atrial natriuretic factor (ANF).

Six different standards for determination of atrial natriuretic factor (ANF) in human plasma samples have been compared using our radio-immunoassay for ANF: International standard 85/669, National Biological Standard Boards, UK; Bachem standard, Torrance, USA; Bachem standard, Bubendorf, Switzerland; Bissendorf standard, Wedemark, Germany; Peninsula standard, Belmont, USA; UCB-Bioproducts standard, Brussels, Belgium. Standard curves obtained with different preparations were in parallel but showed considerable quantitative differences. Standard curves referring to the Bissendorf standard and the International standard, respectively, were almost identical. The dose required for 50% of binding inhibition (ID50s) determined with the Peninsula, UCB and Swiss Bachem standards were higher and ID50 for the American Bachem standard was much lower than ID50 for the International standard. In consequence, estimates of the ANF content in human plasma samples with different standard preparations as the reference showed a considerable variability. With the international standard as the gold reference (plasma ANF concentration 100%) the apparent plasma ANF concentrations measured with the other reference preparations varied from 42% to 178%.

Atrial Natriuretic Factor

Effects of hyperglycaemia on kidney function, atrial natriuretic factor and plasma renin in patients with insulin-dependent diabetes mellitus.

In normoalbuminuric patients with insulin-dependent diabetes mellitus, plasma atrial natriuretic factor (ANF), cyclic GMP and active renin and the renal clearances of [99Tcm]-diethylenetriaminepentaacetic acid (DTPA) lithium and sodium were studied on a hyperglycaemia day and a euglycaemia day. Baseline euglycaemia was achieved by an overnight variable insulin infusion, which during study days was fixed at the rate necessary to maintain euglycaemia in the morning. After a baseline euglycaemic clearance period of 90 min, measurements were repeated in a new 90-min period beginning 150 min later. On the hyperglycaemia day i.v. infusion of 20% glucose was started at the end of the euglycaemic baseline period, increasing blood glucose (5.3 +/- 1.3 vs 12.1 +/- 1.2 mmol l-1, p less than 0.01). On the euglycaemia day blood glucose declined (5.1 +/- 1.0 vs 4.2 +/- 1.0 mmol l-1, p less than 0.02). Glomerular filtration rate (GFR) was unchanged by acute hyperglycaemia (127 +/- 16 vs 129 +/- 24 ml min-1, NS), but nearly normalized during maintained euglycaemia on the euglycaemia day (124 +/- 17 vs 105 +/- 16 ml min-1, p less than 0.01). When comparing the hyperglycaemic study period with the similarly timed period on the euglycaemia day, GFR was elevated by hyperglycaemia (129 +/- 24 vs 105 +/- 16 ml min-1, p less than 0.01), while the renal clearances of lithium and sodium were similar. Consequently, the calculated absolute proximal reabsorption rate of sodium and water was elevated during hyperglycaemia. Hyperglycaemia reduced the slight decline in plasma concentrations of ANF and cyclic GMP observed on the euglycaemia day. Active renin, glucagon and plasma osmolality were unchanged. In conclusion, marked changes in glomerular filtration rate are induced by changes in blood glucose concentration, but the effect is delayed and thus not directly related to renal tubular transport of glucose. Hyperglycaemia does not affect renal clearances of lithium and sodium, while proximal tubular reabsorption is markedly stimulated. These changes are not related to changes in ANF, renin, glucagon or plasma osmolality.

Adult

Onchocerciasis distribution and severity in five West African countries.

The Onchocerciasis Control Programme in West Africa recently extended its operation to Guinea, Guinea-Bissau, the western part of Mali, Senegal and Sierra Leone. To estimate the number of people infected and blinded by the disease and to determine its distribution and severity in the extension area, 215 villages were selected, using a stratified random sampling procedure, and surveyed. All the relevant entomological information available at the time was used in the sampling procedure and in the selection of 92 non-representative villages that were surveyed to confirm the findings. In addition, the populations of 608 villages were examined to map out in detail the distribution of onchocerciasis in the areas at a high risk of onchocercal blindness. The study estimated that 1,475,367 people were infected and 23,728 were blinded from onchocerciasis out of a rural population of 4,464,183. The northern and western part of the study area and the lower Niger basin presented a low or no risk of onchocercal blindness. The upper Niger basin, the south-central part of Sierra Leone, and three small foci in the Gambia, Bakoye, and lower Niger river basins were areas with a high risk of onchocercal blindness. The other parts of the study area presented a medium risk of onchocercal blindness. By detecting the communities at risk of onchocercal disease this study permits the selection of populations for disease control based on mass distribution of ivermectin, a microfilaricide.

Gambia

Enhanced fractional sodium reabsorption in the ischaemic kidney revisited with lithium as a probe.

Extraction of lithium and 51Cr-EDTA across each of the two kidneys was determined during renal vein catheterization in 14 hypertensive patients with unilateral or bilateral renovascular disease before and after i.v. injection of furosemide. Before the administration of furosemide an increased fractional lithium reabsorption was demonstrated across the affected, or more affected kidney. This difference was abolished by furosemide. Using lithium as a probe for sodium, our data suggest an increased fractional tubular sodium reabsorption in the ischaemic human kidney probably located to the proximal tubules as well as to the loop of Henle. Determination of single-kidney fractional lithium reabsorption holds promise as a new research tool for future evaluation of functional abnormalities during divided renal function studies.

Absorption

Assessment of musical processing in brain-damaged patients: implications for laterality of music.

Reception and production aspects of musical ability were assessed in two studies of left cerebro-vascular accident (LCVA) and right cerebro-vascular accident (RCVA) patients and controls. Musical tasks included perception of rhythm and pitch variations in familiar and unfamiliar tunes; and production of a well-known song, three original melodies, and imitation of rhythm patterns. The only "laterality of music" effect to emerge in the first study was impaired ability in LVCA patients to correctly perceive rhythmic changes. In the second study LCVAs were poorer than the other two groups in the singing of novel melodies, and both lesioned groups were poorer than controls in singing a familiar tune and in tapping rhythms. Premorbid musical ability was significantly related to performance over all groups combined. The RCVA group showed an inconsistent pattern of performance. The LCVA group was consistently more impaired over all tasks but apart from the aforementioned effects this was nonsignificant. It is argued that laterality effects for music processing cannot be reliably established.

Aged

Diurnal monitoring of blood pressure and the renin-angiotensin system in hypertensive patients on long-term angiotensin converting enzyme inhibition.

The temporal blood pressure course and the diurnal profile of the renin-angiotensin system were examined in 13 patients with essential hypertension receiving hydrochlorothiazide and enalapril once daily. Blood samples were taken and blood pressure was measured before the habitual morning dose of hydrochlorothiazide and enalapril (at 8.00 a.m.) and at seven time points over the next 24 h. During the period of maximal effect of enalapril (from 11.00 a.m. to 2.00 p.m.), the increase in plasma renin concentration ranged from no change to an 800% increase. A negative correlation was observed between an increase in plasma renin and a decrease in immunoreactive plasma angiotensin II concentration (Spearman rank-order correlation coefficient = 0.83). Notably, the greatest changes in plasma renin and angiotensin II concentrations after enalapril were seen in those patients whose blood pressure fell most during the day. We conclude that hypertensive patients on long-term therapy with enalapril once daily vary widely in their between-dose biochemical response to the drug, and that there is a significant association between the responsiveness of the plasma renin-angiotensin system and the effect on 24 h blood pressure.

Angiotensin-Converting Enzyme Inhibitors

Does the decrease in heart rate prevent a detrimental decrease of the end-systolic volume during central hypovolemia in man?

Central hypovolemia occurring with epidural anesthesia was investigated by measurement of hemodynamic and endocrine variables in 10 patients. Responses fell into two categories. Four patients experienced a hypotensive bradycardic episode after seventeen +/- four minutes. In this group epidural anesthesia initially induced a tendency toward an increase in heart rate from 65 +/- 4 to 73 +/- 5 beats/min concomitantly with decreases in end-diastolic (172 +/- 22 to 138 +/- 16 mL), end-systolic (67 +/- 12 to 51 +/- 9 mL), and stroke (105 +/- 10 to 85 +/- 7 mL) volumes (radionuclide cardiography). A subsequent decrease in mean arterial pressure from 76 +/- 3 to 67 +/- 4 mmHg was associated with a decrease in venous return as reflected by the decrease in cardiac output from 6.1 +/- 0.4 to 4.7 +/- 0.7 L/min. In this situation when the venous return was critically reduced, the heart rate was 49 +/- 4 beats/min and no further reduction in end-diastolic and end-systolic volumes was observed. The observed endocrine changes were compatible with a response to central hypovolemia. In the other 6 patients the reaction to epidural anesthesia did not induce statistically significant changes in hemodynamic and endocrine variables. It is concluded (1) that the decrease in heart rate associated with central hypovolemia during epidural anesthesia seems to be elicited when the left ventricular end-systolic volume is decreased by about 25% and (2) that a further decrease in end-systolic volume during progressive central hypovolemia is avoided possibly as a direct consequence of the slowing of the heart.

Adult

Solid-phase double-antibody radio-immunoassay for atrial natriuretic factor.

A solid-phase radio-immunoassay for the determination of atrial natriuretic factor (ANF) in human plasma is described. Iodination of alpha hANF was carried out with the iodogen method. Purification of radio-iodinated alpha hANF was performed by chromatography on disposable columns of DEAE-Sephadex A-25. Studies of immunoreactivity and the elution pattern on HPLC showed perfect stability of the labelled compounds. The tracer was usable for 28 weeks after preparation, and the batch-to-batch variation in the quality of the tracer was satisfactory. Immunoreactive ANF was extracted from human plasma with Sep-Pak C18 cartridges. Recovery of alpha hANF added to whole blood was 85 +/- 12% (mean +/- SD, n = 12). The sensitivity of the radio-immunoassay was 1.6 pg/tube, equivalent to 1 pg/ml plasma when assaying the extract from 4 ml plasma. Mean plasma ANF values in normal subjects in the supine position was 23 +/- 12 pg/ml (mean +/- SD, n = 21).

Atrial Natriuretic Factor

Captopril treatment in Bartter's syndrome.

A 13-year-old girl presented with lassitude, polyuria and hypokalemia. Plasma renin concentration and urinary prostaglandin excretion were elevated, whereas plasma aldosterone concentration, urinary aldosterone excretion and blood pressure were normal. A diagnosis of Bartter's syndrome was made. The result of treatment with oral potassium was unsatisfactory. Treatment with acetylsalicylic acid had some effect, but an allergic reaction rendered withdrawal necessary. Treatment with the angiotensin converting enzyme inhibitor captopril and oral potassium led to clinical and biochemical improvement.

Adolescent

Normal renal tubular response to changes of sodium intake in hypertensive man.

In a comparative study the influence of changes in dietary sodium intake on blood pressure, renal function, extracellular fluid volume, the renin-angiotensin-aldosterone system and plasma concentrations of arginine vasopressin, atrial natriuretic factor and cyclic guanosine monophosphate (GMP) was investigated in 12 patients with essential hypertension and in 10 normotensive controls. The subjects were studied after 4 days on a low (50 mmol/day), medium (180 mmol/day) or high (380 mmol/day) sodium intake. Renal sodium handling was assessed by simultaneous measurements of 51Cr-ethylenediaminetetraacetic acid (EDTA), lithium and sodium clearances. Identical values for the extracellular fluid volume, glomerular filtration rate and proximal and distal tubular resorption rates of sodium and water were found in the hypertensive patients and the controls at all three levels of sodium intake. In both groups, raising the sodium intake from low to high significantly increased 51Cr-EDTA and lithium clearance (an indirect measure of end-proximal fluid delivery), with intermediate values for the medium-sodium diet. The estimated values of fractional proximal and distal sodium resorption decreased when sodium intake was raised; the absolute proximal sodium resorption rate did not change, whereas the absolute distal sodium resorption rate as well as the extracellular fluid volume and sodium clearance increased. Blood pressure and the heart rate were unaffected by sodium intake. In both hypertensives and controls, plasma concentrations of active renin, angiotensin II and aldosterone decreased with increasing sodium intake, arginine vasopressin did not change, and atrial natriuretic factor and cyclic GMP increased.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult