Donald R. Taves

Separation of fluoride by rapid diffusion using hexamethyldisiloxane.

The presence of hexamethyldisiloxane greatly accelerates the diffusion separation of fluoride, making it possible to recover > 97% of radioactive fluoride in one hour at room temperature. Agitation, and concentration of the acid and alkaline solutions, affect the rate of diffusion. The presence of biological material has little effect on the rate of diffusion. Sulphate and phosphate do not diffuse under these conditions.

Determination of submicromolar concentrations of fluoride in biological samples.

The fluorescence of a Morin-thorium complex provides a more sensitive fluoride reagent than has been previously used. It has immediate stability and a linear response to fluoride up to 50% reduction in fluorescence. The values for serum fluoride, as measured with this reagent after diffusion at room temperature, agree with those obtained with the fluoride electrode and with those predicted by the renal clearance of radioactive fluoride. The relative standard deviation when measuring 10(-6)M fluoride in 2 ml of serum is +/-10%.

Etiology of hyperparathyroidism and bone disease during chronic hemodialysis: I. Association of bone disease with potentially etiologic factors

The present study was prompted by the observation that, in patients with chronic renal failure being followed at this center, renal osteodystrophy developed almost exclusively in those who were treated by chronic hemodialysis at home rather than in our center. A systematic comparison was made between the 10 patients with roentgenographic evidence of the bone disease and 18 patients without demonstrable bone disease. The two groups were similar in age, sex, nature of renal disease, and duration of dialysis. The mean duration of kidney disease was almost 2 yr longer in the patients without bone disease than in those with bone disease. Other significant differences related to where the hemodialysis was performed and to the calcium concentration in the dialysate (6.0-7.4 mg/100 ml in the hospital and 4.9-5.6 mg/100 ml at home). If the unknown factors related to where the dialysis was performed were of no consequence, the major factor contributing to the production of bone disease observed in these patients was the use of a dialysate with a calcium concentration less than 5.7 mg/100 ml.

Dietary intake of fluoride ashed (total fluoride) v. unashed (inorganic fluoride) analysis of individual foods.

Fluoride content in ninety-three individual food items from a hospital in a fluoridated area was determined by ashing (total fluoride) v. unashing (inorganic fluoride) analysis. No discrepancy between the two methods was found by food group but two dry cereals and black pepper did show significantly more fluoride after ashing. The reason for the unavailability before ashing was not determined. Daily fluoride intake was estimated at 1.783 mg which is midway between the 1.211 and 2.201 mg reported from studies in which composite diets were analysed. Daily intake from food at 0.4 mg was one-quarter of the daily total intake 1.8 mg; a ratio consistent with those previously reported in serum, urine and bone between residents from a non-fluoridated v. fluoridated community.

Fluoride concentrations in the human placenta and maternal and cord blood

Abstract Fluoride concentrations in maternal and cord blood were measured for the first time with a method specific for inorganic fluoride. The concentrations averaged 0.88 μM in blood from 16 mothers and 0.68 μM in the cord blood, with a correlation of 0.86. These results are consistent with the hypothesis that fluoride diffuses passively across the placenta. The term placenta, as previously reported, can have much higher concentrations (average 50 μM), but the acid-stable organic fluoride averaged only 4 μM, which is similar to the valves found in human sera.

Factors controlling calcification in vitro: Fluoride and magnesium☆

Abstract Fluoride has been reported to cause both inhibition and enhancement of calcification in vitro . However, those experiments all employed nonphysiological concentrations of at least one of the important ions, and in addition differed too much in experimental design to make it possible to evaluate the variables properly. In this study it was possible to obtain crystal formation with physiological concentrations of calcium, phosphate, fluoride, and magnesium at pH 7.4 and 37 °C by means of nucleators and to note both enhancement and inhibition of crystal formation so that the important variables could be identified. The product of the calcium and phosphate concentrations was the single most important variable; with products just below those found in adult humans there was enhancement by fluoride while with higher products there was inhibition. Contrary to previous reports, magnesium was not required in order to show inhibition. It was also shown for the first time that the concentrations of fluoride normally found in serum can enhance calcification in the presence of physiological concentrations of magnesium if the product of the calcium and phosphate concentrations is lower than normal. These findings suggest that normal serum concentrations of fluoride can act as a governor on the rate of calcification with fluctuations in the serum phosphate concentration, enhancing when the phosphate is low and inhibiting when it is high. Higher fluoride concentrations show more enhancement and less inhibition.

Fluoride-Induced Diuresis: Plasma Concentrations in the Rat

Summary The rates of urine flow and the plasma fluoride concentrations were measured in anesthetized rats receiving continuous infusions of graded levels of fluoride in isotonic solutions. Infusion of 500 nmoles of fluoride/min produced the maximum diuresis, three times the mean control urine flow rate, and a plasma fluoride concentration of 272 μM. The 100 nmoles/min fluoride infusion rate produced an 80% increase in urine flow rate with a plasma fluoride concentration of 56 μM. These findings are consistent with estimates made for man and with the suggestion that the nephrotoxicity following methoxyflurane anesthesia is at least in part due to metabolism of methoxyflurane to inorganic fluoride.

Toxicity following methoxyflurane anaesthesia

SummarySeven obese and five normal weight patients were studied before, during and after one hour of methoxyflurane-nitrous oxide anaesthesia during peripheral surgical operations and compared with eight patients of normal weight anaesthetized with nitrous oxide-meperidine and d-tubocurare. Estimates were made of renal function, including serum and urinary electrolytes, osmolarity, uric acid, urea and Creatinine. Renal clearances for the latter three substances were also calculated. Serum and urinary inorganic and organic fluoride concentrations were measured, as were renal clearances. This low dose methoxyflurane anaesthesia resulted only in a decrease in uric acid clearance among all the measures, when compared to the meperidine-nitrous oxide controls. The clearance of uric acid remained depressed for longer in the obese patients, but otherwise they did not differ from the normal weight patients. It is possible but not proven that depressed uric acid clearance may be related to the organic fluoride metabolite and an early indicator of methoxyflurane renal toxicity. The previously documented biotransformation of methoxyflurane was seen in this study. A double peak in serum inorganic fluoride was shown in all patients but one. Rather large differences in peak levels of serum inorganic fluoride occurred. The only significant difference between the obese and normal weight patients as far as fluoride metabolism was concerned was a greater variability in the serum inorganic fluoride levels in the obese patients. It would appear that the obese patient metabolizes methoxyflurane in a quantitatively if not qualitatively different fashion than the normal weight patient, perhaps because of fatty infiltration of the liver. Caution is advised in the use of methoxyflurane for more than 90 minutes of low concentration administration in view of the unpredictability of the biotransformation.RésuméDouze patients dont sept obèses et cinq normaux, soumis à une chirurgie extraabdominale, ont été étudiés avant, durant et après une heure et demi d’anesthésie à faible concentration de méthoxyflurane et protoxyde d’azote. Une comparaison a été faite avec huit sujets normaux anesthésiés au N2O, mépéridine et d-tubocurare. Les fonctions rénales ont été estimées y compris les électrolytes sériques et urinaires, l’osmolarité, l’acide urique, l’urée et la Créatinine. Les clearances des trois dernières substances ont été mesurées ainsi que les concentrations sériques et urinaires du fluor inorganique et organique et leur clearance.Parmi toutes les mesures faites, seule la clearance de l’acide urique a diminué avec cette petite concentration de méthoxyflurane par comparaison à celle observée après anesthésie à la mépéridine avec protoxyde d’azote. La clearance de l’acide urique demeure basse plus longtemps chez les obèses. Par ailleurs, ceux-ci ne différent pas des patients normaux. Il est possible, bien que non prouvé, que cette dépression de la clearance d’acide urique soit due à la formation de métabolite du fluor et qu’elle puisse servir comme indice précoce de toxicité rénale du méthoxyflurane.La biotransformation du méthoxyflurane qui a déjà été documentée, a été retrouvée dans cette étude. Le graphique des modifications du fluor inorganique a montré chez tous les patients, sauf un, une courbe à double crête.On a constaté des différences relativement prononcées dans les concentrations de pointe du fluor inorganique. En ce qui concerne le métabolisme du fluor, une grande variabilité dans le taux de fluor inorganique sérique chez les obèses était la seule différence observée entre ceux-ci et les patients normaux.Il semble que le patient obèse metabolise le méthoxyflurane d’une façon quantitativement sinon qualitativement différente du patient normal, peut-être à cause d’une infiltration graisseuse du foie.On recommande la prudence, même lors de l’usage d’une faible concentration de méthoxyflurane pour une anesthésie de durée supérieure ou égale à 90 minutes, en raison d’un taux de biotransformation dont l’importance est difficile à prévoir.

Bone fluoride concentrations associated with fluoridated drinking water

SummaryRecently published bone fluoride values from Iowa are very high compared to earlier reports, suggesting an increase in fluoride intake. Reanalysis of the Iowa specimens shows levels one-fourth those reported by the Iowa laboratory indicating an error in the original report. Seventeen bone specimens, collected from long-term residents of Rochester, New York, drinking 1 ppm F− water, had a mean value of 2085±270 ppm F− on an ashed-weight basis. This value is not significantly different from that predicted by the data of Zipkin et al. in 1958. These data, therefore, do not support the contention that there has been an increase in fluoride intake.

Fluoridation and mortality due to heart disease

STANDARDISED death rates in the US, due to ischaemic heart disease stopped increasing and began to decrease during the period in which large numbers of cities began fluoridating their water supplies but no notice has been taken of this effect. Gordon and Thom1 note that deaths attributable to ischaemic heart disease had been increasing until about 1960. By 1968, a clear decrease had begun, and continued until their last observations in 1972. They felt that this decrease (7.3%) could be partially explained on the basis of less severe influenza epidemics, which are thought to increase the mortality rates due to heart disease in the winter months. However, artificial fluoridation was started in 1952, and by 1969 had covered 74 million people2. Therefore, the possibility exists that fluoridation might be involved in the declining rates. Ideally, this would be checked by comparing the rates for ischaemic heart disease between fluoridated and non-fluoridated populations. The largest political units in which the distinction between fluoridated and non-fluoridated populations is clear-cut are cities; unfortunately, ischaemic heart disease is not tabulated separately for cities in the Vital Statistics publication. Ischaemic heart disease is an important part of the category ‘all heart disease’, and those data are readily available. We report here on changes in the more inclusive category (all heart disease) and fluoridation status, which support the possibility that fluoridation is associated with the decreasing rates.