McLean was a second-year medical student at Johns Hopkins University, and was working under the guidance of Howell investigating pro-coagulant preparations, when he isolated a fat-soluble phosphatide anticoagulant in canine liver tissue. In 1918, Howell coined the term heparin for this type of fat-soluble anticoagulant. In the early 1920s, Howell isolated a water-soluble polysaccharide anticoagulant, which he also termed heparin, although it was different from the previously discovered phosphatide preparations. McLeans work as a surgeon probably changed the focus of the Howell group to look for anticoagulants, which eventually led to the polysaccharide discovery. In the 1930s, several researchers were investigating heparin. Erik Jorpes at Karolinska Institutet published his research on the structure of heparin in 1935, which made it possible for the Swedish company Vitrum AB to launch the first heparin product for intravenous use in 1936. Between 1933 and 1936, Connaught Medical Research Laboratories, then a part of the University of Toronto, perfected a technique for producing safe, nontoxic heparin that could be administered to patients, in a saline solution. The first human trials of heparin began in May 1935, and, by 1937, it was clear that Connaughts heparin was safe, easily available, and effective as a blood anticoagulant. Prior to 1933, heparin was available in small amounts, was extremely expensive and toxic, and, as a consequence, of no medical value.Heparin production experienced a break in the 1990s. Until then, heparin was mainly obtained from cattle tissue, which was a by-product of the meat industry, especially in North America.
Metastatic calcification is deposition of calcium salts in otherwise normal tissue, because of elevated serum levels of calcium, which can occur because of deranged metabolism as well as increased absorption or decreased excretion of calcium and related minerals, as seen in hyperparathyroidism. In contrast, dystrophic calcification is caused by abnormalities or degeneration of tissues resulting in mineral deposition, though blood levels of calcium remain normal. These differences in pathology also mean that metastatic calcification is often found in many tissues throughout a person or animal, whereas dystrophic calcification is localized. Metastatic calcification can occur widely throughout the body but principally affects the interstitial tissues of the vasculature, kidneys, lungs, and gastric mucosa. For the latter three, acid secretions or rapid changes in pH levels contribute to the formation of salts. Causes
Hypercalcemia, elevated blood calcium, has numerous causes, including
Elevated levels of parathyroid hormone due to hyperparathyroidism, leading to bone resorption and subsequent hypercalcemia by reducing phosphate concentration. Secretion of parathyroid hormone-related protein by certain tumors. Resorption of bone due to
Primary bone marrow tumors (e.g. multiple myeloma and leukemia)
Metastasis of other tumors, breast cancer for example, to bone. Paget disease
Immobilization
Vitamin D related disorders
Vitamin D intoxication
Williams syndrome (increased sensitivity to vitamin D)
Sarcoidosis
Kidney failure


== References ==