Evan Calkins

AMYLOIDOSIS: PRELIMINARY CLINICAL, CHEMICAL, AND EXPERIMENTAL OBSERVATIONS*

Although it has been an object of clinical, pathological and, more recently, chemical studies over the course of the past seventy-five years, amyloidosis remains one of the more intriguing enigmas in medicine. As a subject for clinical investigation, this disease is appealing for several reasons. First, it can be produced experimentally in Second, amyloid is accumulated in tissues in sufficient abundance to make its availability for chemical characterization appear a reasonable objective. Third, it is a disease of considerable clinical importance. Thus amyloidosis is a common concomitant of rheumatoid arthriti~;~.’ it is a common cause of death of patients with paraplegia, chiefly because of the severe decubitus ulcers and osteomyelitis that often accompany it;8 it is the most important single cause of death of patients with leprosy (unpublished observations, in preparation). I t often accompanies multiple myeloma and, not infrequently, occurs without known predisposing disease, especially in certain Mediterranean countries where two familial forms are indigenous? JO Surely a disease with these characteristics should prove an easy one to understand. This has not proved, however, to be the case. The nature of amyloid is still obscure, the reasons for its diverse origins is unknown, the pathogenesis of none of its forms is understood, and means of its prevention and cure are still uncertain. Approximately six years ago several workers in this laboratory undertook a long-range study of the disease in the hope that what was learned would be helpful in gaining understanding not only of amyloidosis, but also of the even more puzzling diseases of connective tissue that often underlie it. Some of this work has been published, some is in manuscript form, and some is still in progress and permits mention of only the most preliminary conclusions. Nevertheless, as an example of one area in which research in connective tissue is reaching clinical application, a brief and rather general review of the problem may be welcome. Since our studies have been focused along three lines, clinical, chemical, and experimental, it may be helpful a t the outset to emphasize two clinical points. The first pertains to classification. Amyloidosis is often classified into specific types by rather rigid criteria.ll-l* It is said, for example, that “primary” amyloidosis is characterized by predominant involvement of the mesenchymal tissues (blood vessels, skin, heart, tongue, gastrointestinal tract, and nerves),

Metabolism and clinical significance of the carbohydrate components of connective tissue.

CARBOHYDRATE is necessary in the body, not only as a source of energy but also as an integral part of its structure and functional components, connective-tissue matrix, nucleic acids, galactolipids...

IDIOPATHIC FAMILIAL OSTEOPOROSIS IN DOGS: “OSTEOGENESIS IMPERFECTA”

Osteogenesis imperfecta is a disease that occurs in small animals, especially members of the cat family, as well as in human beings.’ Chance development of this condition in 6 of 7 members of a litter of standard poodle puppies several years ago provided an opportunity for study. Since that time we have been able to follow 2 other litters: 1, also of poodles, in which 4 of 12 puppies had the disease; and a second, of Norwegian elkhounds, of which 3 of 6 puppies had the disease. The diagnosis was confirmed in each instance by X ray of the extremities, which showed the changes characteristic of the disease. Several of the clinically uninvolved siblings studied by X ray were normal, except for evidence of mild rickets in 1. Each of the 13 involved dogs displayed a clinical picture manifested by numerous pathological fractures and by the development of deformities. The fractures, usually occurring with minimal trauma, healed a t a rapid rate, even though the dog continued to walk. Only 2 fractures, which occurred after trauma, required splinting. None of the dogs developed pseudoarthroses. The deformities were characterized by a flattening of the front paws and metatarsals to create a “snow shoe” appearance, an outward bowing of the elbows, and severe knock knees. I t should be emphasized that these deformities are seen in other bone diseases in dogs, such as rickets,’ or osteoporosis associated with copper deficiency: and are not specific for osteogenesis imperfects . Despite the disease, most of the dogs achieved a height within an inch or 2 of their normal siblings. Two of the poodles, however, one from each litter, were decidedly stunted, one at birth, and the other by the time he reached 3 months of age. Except for the 1 runt, all of the dogs appeared to be entirely healthy until 6 to 8 weeks of age, when the bony abnormalities became a p parent.t Physical examinations were negative except for the skeletal system. Although the most severely ill dogs were reluctant to stand on their hind legs, this appeared to be due to pain rather than weakness. The extremities displayed unusual hypermobility. There was no articular involvement. The sclerae did not appear blue and, so far as we could tell, the dogs were not deaf.