Tissue culture of normal and cystic fibrosis sweat gland duct cells. I. Alterations in dome formation.

The elucidation of the underlying defect in fluid secretion by cystic fibrosis (CF) sweat glands is hindered by the unavailability of an experimental model for investigating this disease. As a potential model system, a serum-free growth medium was developed that supports the explant growth of epithelial cells from fragments of human skin. Immunohistochemical analysis demonstrated that these epithelial cell outgrowths originated from the duct of the sweat gland. By electron microscopy, the cells were demonstrated to possess keratinocyte-like morphology as noted by the presence of a multilayered outgrowth of cells containing well-defined keratin bundles. Identical outgrowths from skin biopsies of CF patients were compared to normal outgrowths and alterations were noted to occur in dome formation and in the number of intercellular spaces between cells. Doming alterations were also noted to occur in the CF heterozygous state. No differences in cell fine structure or in growth factor requirements for cell proliferation were noted between normal and CF cells. The potential use of this system as a model for CF research is discussed.

Psychosocial and developmental factors in failure to thrive: one- to three- year follow-up.

Fifteen infants and children with a diagnosis of failure to thrive (FTT) were followed at one to three years postdischarge. Data were gathered from in-home interviews, psychosocial questionnaires, measurement of present height and weight, and administration of the Developmental Profile. Nine of the 15 children were still failing to thrive; the other 6 were considered recovered. The nonthriving group consisted of three subgroups: (1) developmentally retarded, (2) organic basis FTT, and (3) psychosocial FTT. The developmentally retarded children were significantly different in that they required more attention, had greater constipation, and engaged in less tantrum behavior. Further, they were significantly more impaired in the physical, self-help, and social areas of development. The difficulties in diagnosis and treatment of FTT children are discussed. Suggestions for the enhancement of medical management of this complex and life-threatening disorder are offered.

Elevated prostaglandin production in cultured cells from a patient with fibrodysplasia ossificans progressiva.

Prostaglandin E production was measured in cells cultured from both a fibromatoid lesion and a normal area of skin in a patient with fibrodysplasia ossificans progressiva. The synthesis of prostaglandin E-like material (iPGE) was ten- to twenty-fold greater in cells cultured from the patient's fibromatoid lesion than in fibroblasts obtained from her normal skin. Addition of indomethacin in vitro resulted in a greater than 95% reduction of iPGE production in both cell cultures. These observations appear to warrant further investigation in additional patients, with this disease.

Studies on alkaline phosphatase activity cultured cells from a patient with fibrodysplasia ossificans progressiva.

The cytoplasm of tumor cells from a subdermal nodule in a patient with fibrodysplasia ossificans progressiva (FOP) exhibited intense enzymatic activity in cryostat sections processed for demonstration of alkaline phosphatase. Nuclear heterochromatin and nucleoli, particularly in the area of the dense component, also showed strong reactivity. Finely minced blocks from the lesion of the patient with FOP revealed lighter reactivity which, in the tumor cells, avoided membrane limited spaces and appeared to be confined to hyaloplasm. Extracellular spaces disclosed very little or no reactivity and specimens from the patient's uninvolved skin lacked staining. The tumor cells from the subdermal nodule did not exhibit increased acid phosphatase activity. Cells (L-FOP) derived from a subdermal nodule and grown by tissue culture techniques also synthesized large amounts of prostaglandin E-like material and alkaline phosphatase. The amounts of prostaglandin E-like material synthesized by these L-FOP cells was reduced by more than 31 per cent by the antiinflammatory drugs indomethacin and sodium meclofenmate. Also, the production of alkaline phosphatase by these L-FOP cells was reduced by more than 40 per cent by ethane-1-hydroxyl-1,1-diphosphonate. Addition of prostaglandin E to nonlesion cells did not result in increased alkaline phosphatase activity.

Planning for ambulatory care: simple methods for improving patient flow.

A combined patient flow and work sampling study was done at the Ambulatory Pediatric Service of the Medical University of South Carolina. The biggest problem was that almost two thirds of the patient's time was spent waiting to see the doctor. Reasons for delay included too few examining rooms, the single block appointment system, and design of the facility.

Histochemical and ultrastructural studies in fibrodysplasia ossificans progressiva (myositis ossificans progressiva).

By light microscopy the subdermal nodule of a patient with fibrodysplasia ossificans progressiva (FOP) had a fibromatoid histologic appearance. The cytoplasm of the cells stained strongly for mannose-rich glycoprotein with the concanavalin A-horseradish peroxidase (con A-HRP) method. The tumors also exhibited abundant hyaluronidase-digestible mucopolysaccharide in the interstitium with various basic staining reagents. This material appeared to consist principally of hyaluronic acid or chondroitin sulfate with few or mainly masked sulfate esters. At the ultrastructural level, cells interpreted as the tumor cells in the subdermal nodule from the patient displayed extremely hyperplastic granular reticulum and well-developed Golgi elements and appeared very active in synthesis and secretion of protein. The material in the dilated cisternae of the granular reticulum stained for glycoprotein with the con-A-HRP method. Macrophages which comprised the other main cell type in the nodules commonly contacted the tumor cells and occasionally evidenced engulfment of these cells. The intercellular matrix of the nonossified subdermal nodule exhibited greatly increased mucosubstance and, by electron microscopy, showed an unusual network of dialyzed iron-reactive acid muco-substance in the interstitium.