Thesis (Ph. D.)--Columbia University, 1926. / Vita. Bibliography: p. [19].

Inaug.-diss.--Leipzig. / Lebenslauf.

Thesis (M.S.)--University of Wisconsin--Madison. / Typescript. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 37-45).

Mainz, Universiẗat, Diss., 2005.

Hannover, Universiẗat, Diss., 2002.

Proefschrift Maastricht. / Lit.opg. - Samenvatting in het Nederlands en Engels.

Th.--Méd.--Paris, 1873. / Voyez : Paris, 1873. Tome 7. N ° 103.

Th. 3e cycle--Phys. nucl.--Grenoble 1, 1979. N°: 35.

The kinetics of plasma calcium regulation in man were studied by noting the response to intravenous injection of calcium as gluconate given at the rate of 10 mg/kg/hr. Twenty-nine infusion tests were carried out on 20 adult male subjects. The series comprised normals, cases of hypoparathyroidism, hyperparathyroidism, Paget's Disease, and osteoporosis. All were hospitalized at the time of the study. The changes in levels of plasma calcium, phosphorus and citrate were followed by frequent blood sampling. Excretion of calcium, phosphorus and citrate by the kidney was also determined. In all cases, plasma calcium levels rose in response to the infusion and declined slowly after it had ended, returning to normal several hours later. Plasma phosphate and citrate also rose slightly, but more slowly than the plasma calcium, and remained elevated as long as plasma calcium was above normal. The increase in the calcium excretion rate was directly proportional to the plasma calcium during the period of hypercalcemia. From this linear relationship it was possible to estimate a tubular maximum (Tm) for reabsorption of calcium by the renal tubules. The value obtained for calcium Tm in this series of 8 normal subjects was 4.97 ± 0.27 mg/min (range 3.60 – 5.80). In the one case of osteoporosis studied, the Tm appeared to be increased following correction of a hyperchloremic acidosis. The increased calcium excretion during hypercalcemia is a most important homeostatic factor in restoring the plasma level to normal. The rapidity of the exchange between the bone and the soft tissue calcium compartments appeared to be much greater in the cases of Paget's disease, as might be predicted from the high rate of bone blood flow characteristic of this disease. / Medicine, Faculty of / Cellular and Physiological Sciences, Department of / Graduate

Calcium gluceptate (calcium ɑ-glucoheptonate, CaC₁₄,H₂₆O₁₆) occurs as a crystalline hydrate (I) containing 3 1/2 molecules of water of crystallization per atom of calcium or as an amorphous anhydrate(III). Calcium gluceptate was synthesised commercially as III until 1980 but since then only I has been commercially available. The maximum aqueous solubility of III at room temperature was found to be > 2 molal while the equilibrium solubility of I at 25.5°C was 0.06 molal (≃3.3% w/v). A crystalline anhydrate (II) wtiich had an apparent water solubility of 1.3 molal was prepared from I by dehydration. The United States Pharmacopeia (USP) injection is an aqueous solution containing 20.8 to 23.3% w/v CaC₁₄H₂₆O₁₆ which is greater than the equilibrium solubility. Solutions prepared using II or III were supersaturated with respect to I and crystallized on storage. Pharmaceutically stable solutions could be prepared from II by autoclaving the solutions at 121°C for 20 minutes immediately after preparation which presumably destroyed seed crystals of I. When stored at relative humidities (RH) greater than 66% at 25°C, II was converted into I and the reverse process occurred at 0% RH. Above 0% and below 66% RH neither I nor II underwent a phase transition during one year of storage. The co-existence of I and II over a range of RH would be contrary to the phase rule. It is suggested that at RH less than 66%, the adsorption of a small amount of. atmospheric water vapor inhibits the II to I transition probably due to the formation of a surface layer of I which limits further diffusion of water. In addition to the phase transformations in aqueous solution and the dehydration and rehydration reactions, the effects of freeze drying and grinding on the interconvertibility of I, II and III were studied. On grinding II for increasing times, there were marked increases in apparent water solubility, decreases in the intensity of x-ray diffraction peaks, and heats of solution changed from endothermic to exothermic. The results were attributed to decreases in crystallinity, since surface area measurements showed that they could not be due to particle size reduction. Density is independent of particle size, and values obtained for II using a liquid suspension method changed progressively with grinding. The x-ray diffraction, calorimetric and density measurements were used both to quantify the degree of crystallinity of II and to test various models of crystallinity. According to the USP, solids are crystalline, non-crystalline (amorphous) or a mixture of the two. The degree of crystallinity depends on the fraction of crystalline material in the mixture (two-state model). An alternative concept is that the degree of crystallinity has a value between 100% (perfect crystal) and 0% (amorphous) depending on the state of order/disorder in the lattice (one-state model). It was concluded that grinding decreases the crystallinity of II by increasing lattice disorder according to the one-state model. / Pharmaceutical Sciences, Faculty of / Graduate