Lack of adverse reactions in ivermectin treatment of onchocerciasis.
Explore the source record for details and available documents.
Clinical Trials as Topic↗
Biomedical subjects
J Giese
Publications and source records attributed to J Giese.
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↗
Effect of captopril on blood pressure and kidney function in normotensive insulin dependent diabetics with nephropathy.
OBJECTIVE: To assess whether inhibition of angiotensin converting enzyme protects kidney function in diabetic nephropathy. DESIGN: Open, randomised follow up study of normotensive insulin dependent diabetics with nephropathy either treated or not with captopril for one year. SETTING: Outpatient diabetic clinic in a tertiary referral centre. PATIENTS: 32 Normotensive patients with insulin dependent diabetes complicated by nephropathy who were randomised either to the treatment group (n = 15) or to the control group (n = 17). INTERVENTIONS: The treatment group was given captopril (25-100 mg/day) for 12 months, the average dose during the second six months of the study being 40 mg daily. Controls were not treated. MAIN OUTCOME MEASURES: Albuminuria, arterial blood pressure, and the glomerular filtration rate. RESULTS: Mean arterial blood pressure fell by 3 (SE 2) mm Hg in the captopril treated group and rose by 6 (1) mm Hg in the controls. In addition, albuminuria declined by 11% in the captopril treated group and rose by 55% in the controls, fractional albumin clearance fell by 17% in the captopril treated group and increased by 66% in the controls, and the glomerular filtration rate declined by 3.1 (2.8)ml/min/1.73 m2 with captopril and by 6.4 (3.1) ml/min/1.73 m2 in the controls. CONCLUSION: Inhibition of angiotensin converting enzyme arrests the progressive rise in albuminuria in normotensive insulin dependent diabetics with nephropathy.
Adult↗
Effects of insulin on kidney function and sodium excretion in healthy subjects.
Insulin action on kidney function was evaluated in 8 healthy subjects, (mean age 27 years) using the euglycaemic clamp technique. Insulin was infused at rates of 0, 20 and 40 mU.min-1.m-2 over consecutive periods of 120 min resulting in plasma insulin concentrations of 8 +/- 2, 29 +/- 7 and 66 +/- 14 mU/l. The renal clearance of 51Cr-EDTA, lithium, sodium and potassium was determined during the last 90 min of each period. Sodium clearance declined with increasing plasma insulin concentrations (1.3 +/- 0.4, 1.0 +/- 0.3 and 0.5 +/- 0.2 ml.min-1.1.73 m-2, p less than 0.001), while glomerular filtration rate (108 +/- 21, 104 +/- 21 and 108 +/- 20 ml.min-1. 1.73 m-2) and lithium clearance (a marker of fluid flow rate from the proximal tubules) 29 +/- 5, 29 +/- 4 and 30 +/- 4 ml.min-1.1.73 m-2) remained unchanged. Calculated proximal tubular reabsorption of sodium and water was unchanged, while calculated distal fractional sodium reabsorption increased (95.5 +/- 1.5, 96.4 +/- 1.2 and 98.1 +/- 0.7%, p less than 0.001). Potassium clearance and plasma potassium concentration declined, whereas plasma aldosterone and plasma renin concentrations were unchanged. In conclusion, elevation of plasma insulin concentration within the physiological range has a marked antinatriuretic action. This effect is located distally to the proximal renal tubules.
Adult↗
Bartter's syndrome--treatment with potassium, spironolactone and ACE-inhibitor.
The treatment of Bartter's syndrome is fraught with difficulties, and there is no consensus concerning the pathogenetic mechanisms involved. Potassium depletion with hypokaliaemia is a dominant feature of the syndrome. In this case history, a 42-year-old woman suffering from Bartter's syndrome did not improve on several therapeutic trials. An impressive progress was noted, however, after intensive potassium repletion with subsequent potassium/spironolactone/ACE-inhibitor treatment. After 24 months her condition was unchanged with normal and stable Se-potassium concentration.
Adult↗
Effects of angiotensin blockade on the splanchnic circulation in normotensive humans.
The effects of angiotensin-converting enzyme inhibition (ACE-I) by enalapril on splanchnic (n = 10) and central hemodynamics (n = 9) were examined in moderately salt-depleted healthy volunteers, at rest and during 15-20 min of lower body negative pressure (LBNP), reducing mean arterial pressure by 10 mmHg. During LBNP before ACE-I, both splanchnic and total peripheral vascular resistances increased. During ACE-I, splanchnic and total peripheral vascular resistances decreased. After enalapril administration, splanchnic vascular resistance did not increase during LBNP. Total peripheral vascular resistance still increased but not to the same extent as during LBNP before ACE-I. The increases in heart rate and plasma norepinephrine during LBNP were attenuated after ACE-I compared with LBNP before ACE-I. The effectiveness of the ACE-I was clearly demonstrated by unchanged and low plasma angiotensin II levels during ACE-I. We conclude that, in normal sodium-depleted humans, acute ACE-I decreases splanchnic vascular resistance at rest and abolishes splanchnic vasoconstriction during LBNP. Furthermore, it may interfere with autonomic nervous system control of the circulation.
Adult↗
On the pathogenesis of arterial blood pressure elevation early in the course of diabetic nephropathy.
We measured plasma- and extracellular fluid volume (125I-albumin, 51Cr-EDTA), plasma concentrations of renin, angiotensin I and II, aldosterone and atrial natriuretic peptide by radio-immunoassays in insulin-dependent diabetic (IDDM) patients with (n=28) and without (n=11) nephropathy and in 14 normal control subjects matched for sex and age. Glomerular filtration rate (GFR) (ml/min/1.73 m2, single intravenous bolus 51Cr-EDTA technique) was within normal range in all nephropathic patients; 107 (range 78-134). Mean arterial blood pressure (mmHg) was elevated 102 +/- 13 (+/- S.D.) compared to the diabetic and normal control group, 92 +/- 8 and 87 +/- 5, respectively (p less than 0.01). Plasma volume was identical in all three groups while extracellular volume (1/1.73 m2) was expanded in nephropathic patients, 14.5 +/- 1.5 vs 13.1 +/- 0.9 and 12.4 +/- 1.3 in the diabetic and non-diabetic control groups, respectively (p less than 0.05). A significant correlation between extracellular fluid volume and mean arterial blood pressure was found (n=53, r=0.49, p less than 0.001). Active renin was significantly increased in patients with diabetic nephropathy compared with the normal control subjects, while all the remaining hormones were about the same in the three groups. Our study suggests that fluid retention plays a dominant role in the initiation and maintenance of arterial blood pressure elevation early in the course of diabetic nephropathy.
Adult↗
Unchanged lithium clearance during acute amiloride treatment in sodium-depleted man.
To evaluate the validity of the lithium clearance method as a marker of overall proximal tubular fluid delivery in moderately sodium-depleted humans, the effects of a single dose of 10 mg amiloride on lithium clearance and glomerular filtration-rate were studied in normal volunteers maintained on a sodium diet of 50 mmol/day. Amiloride caused no changes of the glomerular filtration-rate or of lithium clearance. The effects of amiloride on tubular sodium, potassium and water handling were in accordance with a distal tubular action of amiloride. The results suggest that significant distal lithium reabsorption does not occur in measurable amounts during moderate sodium depletion in humans. The lithium clearance method may, therefore, be used to assess proximal fluid delivery in man when dietary sodium intake is as low as in the present study.
Adult↗
Changed cyclic guanosine monophosphate atrial natriuretic factor relationship in hypertensive man.
Plasma concentrations of atrial natriuretic factor (ANF) and cyclic guanosine monophosphate (cGMP) were measured in 10 patients with essential hypertension and 10 normotensive controls on the fifth day of a low (50 mmol/day), a medium (180 mmol/day) and a high (380 mmol/day) dietary sodium intake. Plasma ANF and cGMP concentrations were less on the low than on the high sodium intake. Values for ANF on the medium sodium intake were intermediate. In normotensive subjects cGMP concentrations did not differ significantly on the low and the medium sodium intake. As compared with the controls plasma concentrations of cGMP were significantly increased in hypertensive patients on all three levels of sodium intake, while ANF concentrations were identical in the two groups. Since cGMP is a second messenger to ANF the data suggest an increased cellular response to ANF in patients with essential hypertension.
Adult↗
A community trial of ivermectin in the onchocerciasis focus of Asubende, Ghana. II. Adverse reactions.
A community trial of the microfilaricide ivermectin undertaken in an hyperendemic focus of blinding onchocerciasis in Ghana. One objective was to investigate the safety of this new drug when used in mass treatments. 14,911 persons (61.5% of the census population) were treated with ivermectin. Of these, 15% reported with adverse reactions which were generally similar to those reported in the clinical trials. However, cutaneous reactions were relatively less frequent while brawny oedema of the limbs and inguinal gland pain were important. The severe reactions consisted of 37 cases of Severe Symptomatic Postural Hypotension (SSPH), 13 cases of severe fever and two cases of severe dyspnoea. The latter two cases represented life threatening situations, but there was no evidence that they were complications of ivermectin treatment. Only four of the SSPH cases required treatment. All severe adverse reactions were managed successfully and recovered within one day, usually within a few hours. The incidence of adverse reactions was highest the first day after treatment. Thirteen cases of delayed reactions were reported during a four-week follow-up. There was a highly significant relationship between incidence of adverse reactions and intensity of infection but no relation with ivermectin dosage within the range of 130-200 mcg/kg. The results suggest that ivermectin is sufficiently safe to be used in mass treatments. However, mass distribution of this drug should not be undertaken without adequate monitoring.
Adolescent↗
Adverse reactions after large-scale treatment of onchocerciasis with ivermectin: combined results from eight community trials.
Eight community trials were carried out by the Onchocerciasis Control Programme in West Africa to determine the safety of the new microfilaricide ivermectin during large-scale treatment of onchocerciasis. The trial areas were located in eight different countries and varied greatly in endemicity level; a total of 50,929 persons were treated and monitored for 72 hours. Overall treatment coverage was 60% of the census population, the main reasons for non-treatment being the exclusion criteria. Of those treated, 9% reported with adverse reactions, 2.4% with moderate reactions, and 0.24% with severe reactions. Most reactions were reported during the first day of follow-up, the most frequent severe reaction being severe symptomatic postural hypotension (in 49 cases). Three cases of severe dyspnoea were life-threatening but their relationship with ivermectin treatment is uncertain. The incidence of adverse reactions was directly related to skin microfilarial load and was highest in the foci with the highest endemicity levels. Treatment resulted in 98% reductions in mean microfilarial loads at all endemicity levels. The benefit of treatment largely compensated for the discomfort due to adverse reactions, which were all transient and managed successfully. Ivermectin thus appears to be sufficiently safe for large-scale treatment but monitoring by resident nurses for at least 36 hours is recommended.
Africa, Western↗
Lithium clearance and renal tubular sodium handling during acute and long-term nifedipine treatment in essential hypertension.
1. In two separate studies the lithium clearance method was used to evaluate the influence of acute and long-term nifedipine treatment on renal tubular sodium reabsorption. 2. In the acute study, after a 4 week placebo period two doses of 20 mg of nifedipine decreased supine blood pressure from 155/101 (20.6/13.5) +/- 11/4 (1.5/0.5) to 139/88 (18.5/11.7) +/- 16/9 (2.1/1.2) mmHg (kPa) (means +/- SD; P less than 0.01). Lithium clearance, glomerular filtration rate and sodium clearance did not change. Therefore the calculated values of absolute proximal and absolute distal sodium reabsorption rates were also unchanged, as were potassium clearance, urine flow and body weight. 3. In the long-term study, lithium clearance, glomerular filtration rate, sodium clearance, potassium clearance, urine flow and body fluid volumes were measured after a 4 weeks placebo period and after 6 and 12 weeks of nifedipine treatment. As compared with placebo, mean supine blood pressure decreased significantly. The glomerular filtration rate did not change but lithium clearance fell by 30%. Consequently, the absolute and the fractional proximal sodium reabsorption increased significantly. The fractional distal sodium reabsorption did not change. Sodium clearance, fractional sodium excretion, potassium clearance, plasma volume and extracellular fluid volume were also unchanged. 4. In conclusion, we found no changes of renal tubular sodium reabsorption during acute nifedipine treatment, whereas long-term nifedipine treatment caused a redistribution of tubular sodium reabsorption without a change in overall sodium excretion or body fluid compartments.
Absorption↗