Formate kinetics in methanol poisoning

OBJECTIVE: We sought to describe the kinetics, dialysis clearance, and laboratory markers of formate (FA), the toxic metabolite of methanol (meOH). METHODS: Data were obtained from a prospective, multicenter study of fomepizole +/- dialysis for methanol poisoning. Inclusion criteria confirmed methanol exposure or suspicion of exposure plus either acidemia or abnormal osmolar gap. Dialysis indications were [meOH] > 50 mg/dL, pH < 7.1, refractory acidosis, or visual toxicity. Serial plasma formate, methanol, pH, and electrolyte measurements were made. Formate was determined by gas chromatography. Endogenous and dialysis elimination half-lives were calculated as t(1/2) = 0.693/Ke, with Ke (elimination constant) derived from the slope of log (FA) vs. time. Half-lives were compared with an unpaired Student's t-test. Dialysis clearance was calculated using the Fick Principle. Pearson correlation analysis compared initial formate with initial pH, serum bicarbonate, and anion gap. RESULTS: Eleven patients were treated in the study. Eight had detectable formate with mean [FA] of 15.1 mmol/L (range 0.5-34.8). Endogenous elimination half-life was 205 +/- 90 minutes. Elimination half-life during dialysis (n = 5) was 150 +/- 37 minutes, which was not different (t = 0.22; NS). The overall dialysis formate clearance rate was 223 +/- 25 mL/min. Correlation coefficients were: pH vs. formate r2 = 0.93; bicarbonate vs. formate r2 = 0.81; and anion gap vs. formate r2 = 0.76 (all p < 0.05). CONCLUSIONS: Although dialysis clears formate, it did not significantly enhance endogenous elimination in our series of patients. Low pH, low bicarbonate, and elevated anion gap correlate independently with formate presence.     

Urinary Excretion of Kallikrein before and after Operation for Aldosterone-producing Adenoma

ABSTRACT. Hesse B, Rasmussen S, Lund JO, Christensen P, Damkjær Nielsen M. (Department of Clinical Physiology, Glostrup Hospital, and Institute for Experimental Medicine, Copenhagen, Denmark.) Urinary excretion of kallikrein before and after operation for aldosterone-producing adenoma. Urinary kallikrein excretion (UKal), determined by the esterase method, was measured in 10 normotensive volunteers, 10 patients with essential hypertension and in 7 patients with primary aldosteronism before and after operative removal of the adenoma. UKal values were low in 5 of the patients with essential hypertension. Preoperative UKal values in the patients with aldosteronism did not differ significantly from those of the normal subjects, but decreased in all after operation in parallel with changes in urinary excretion of tetrahydroaldosterone and plasma aldosterone concentration. The study supports the assumption of an association between the renal kallikrein-kinin system and the mineralo-corticoid state in man.     

PSEUDOHYPOALDOSTERONISM Clinical, Biochemical and Morphological Studies in a Long-term Follow-up

ABSTRACT. A boy with pseudohypoaldosteronism was followed from birth to the age of 7 years. Failure to thrive, vomiting, dehydration, hyponatraemia and urinary sodium loss were prominent findings. Urinary excretion of corticosteroid metabolites was normal. Before treatment, excessively high plasma renin concentration was found, associated with a marked activation of aldosterone secretion. A renal biopsy showed pronounced hypertrophy of the juxtaglomerular apparatus. Persisting metabolic acidosis and an insufficient urinary acidifying capacity suggested the presence of distal renal tubular acidosis. Treatment with sodium bicarbonate and sodium chloride from 19 to 31 months of age resulted in normal growth and normal physical and mental development. The plasma electrolytes were normalized but a pronounced activation of the renin–aldosterone system persisted after therapy, and on sodium restriction this system responded with a considerable further activation.     

The renin-angiotensin system during converting enzyme inhibition with captopril in patients with severe treatment-resistant hypertension

Abstract. The effect of captopril on blood pressure (BP) and various components of the renin-angiotensin system was assessed in ten severely hypertensive patients. Captopril acutely reduced the BP with a maximum decrease of 23% at 90–120 min.
Maintenance treatment with captopril alone could not control the BP in any of the patients. Addition of hydrochlorothiazide markedly reduced the BP, while supplementation with propranolol caused no consistent changes.
Three patients attained a supine diastolic blood pressure (SDBP) ≤90 mmHg. Only two patients had a fall in SDBP less than 10 mmHg. One patient stopped because of taste disturbances.
Monitoring the renin-angiotensin system showed suppressed plasma concentrations of angiotensin II and increased levels of angiotensin I and renin, indicating the inhibition of converting enzyme activity. Plasma concentration of renin substrate decreased significantly. This observation has important implications for the methodology of renin assays.
Captropril is an effective alternative in the treatment of hypertensive patients not readily controlled with conventional therapy.     

Converting Enzyme Inhibition in Mild and Moderate Essential Hypertension: I. Acute Effects on Blood Pressure,the Renin-Angiotensin System and Blood Bradykinin after a Single Dose of Captopril

ABSTRACT. The acute effects of 25 mg captopril on blood pressure, heart rate, components of the renin-angiotensin system and blood concentration of bradykinin were followed in a single-blind placebo study of untreated (group A, n = 15) and thiazide-treated (group B, n = 13) patients with mild or moderate essential hypertension. A drug-related fall in blood pressure was seen in both groups. The blood pressure reduction was more marked in group B than in group A. Heart rate remained unchanged. Plasma concentrations of angiotensin II decreased significantly with concurrent increases in plasma concentrations of renin and angiotensin I, indicating the in vivo inhibition of converting enzyme. Blood concentrations of bradykinin showed no systemic changes. The magnitude of blood pressure reduction was correlated both with the pretreatment levels and the concurrent decreases in plasma angiotensin II. Inhibition of angiotensin II formation can explain a large part of the acute hypotensive pharmacological action of captopril. Other vasoactive systems may be involved. The kallikrein-kinin system does not appear to participate as indicated by the unchanged concentrations of kinin in blood.     

Chemical Contamination of Private Drinking Water Supplies in the West Midlands,United Kingdom

Introduction: In the United Kingdom, private drinking water supplies are subject to much less stringent sampling and testing regimes than are public supplies. Information regarding the quality of private drinking water supplies is disparate and poorly defined. The aim of this study was to collate the data for chemical contamination of private drinking water supplies in the West Midlands, a region of Central England with a population of 5.3 million. Methods: The most recent year's data on the number of private supplies, the number of supplies sampled, and the number and type of failures for chemical parameters were obtained from District and Local Authorities in the West Midlands Region. Results: Data covered 12-month periods during 1995–1996. Of the 6013 private supplies identified, samples from 1297 had been tested for chemical parameters during the period of the study. A total of 420 individual failures for chemical parameters were reported in 386 water supplies. The majority of breaches of United Kingdom and European Union standards were due to increased concentrations of nitrates (270), magnesium (21), manganese (17), and iron (15). Increased turbidity was present in 27 cases. Only 6 samples breached the standard for lead and 6 for pesticides. Conclusions: Over a quarter of the supplies tested during the period of the study were in breach of United Kingdom and European Union legislation. Of the reported failures, the high concentrations of nitrate and nitrite, lead, copper, and sulfate are of concern to health and remedial action is warranted. Regular sampling of private drinking water supplies remains necessary to prevent risk to health from a wide variety of toxic contaminants.     

Converting Enzyme Inhibition in Mild and Moderate Essential Hypertension. II

ABSTRACT. In 24 patients with mild/moderate essential hypertension, we studied the effects of captopril with/without hydrochlorothiazide (Htz) on blood pressure, the renin-angiotensin system, blood bradykinin concentration (BBK), plasma volume, exchangeable sodium and glomerular filtration. Daily captopril doses of 75 and 150 mg were equally effective in reducing the blood pressure. Addition of Htz caused further blood pressure reductions. Nineteen patients attained a diastolic blood pressure ≤90 mmHg. Angiotensin converting enzyme inhibition with captopril led to a fall in plasma concentrations of angiotensin II (PAII) and renin substrate, and an increase in plasma concentrations of renin and angiotensin I. Patients starting with Htz had a higher PAII and subsequently a larger fall in blood pressure on captopril than untreated patients. BBK remained unchanged, indicating that the hypotensive action of captopril does not involve an accumulation of circulating kinin. Body fluid volumes and renal function were not affected by the various treatment regimens.