Growth-plate chondrocyte cultures for reimplantation into growth-plate defects in sheep. Characterization of cultures.

Damage to epiphyseal growth plates due to fracture, trauma, or infection can lead to invasion of bone across the cartilage and localized arrest of long-bone growth. The implantation of a viable de novo cartilage plug into such defects may provide the appropriate cartilage presence necessary to inhibit the initial formation of bony bridges across the epiphysis and so maintain the growth potential. De novo cartilage plugs were prepared from ovine growth plates by culturing isolated epiphyseal chondrocytes from fetal lambs. After 14 days of culture, these de novo cartilage discs were composed of chondroitin sulfate, a small amount (5%) of dermatan sulfate, and cartilage-specific collagen. The cellular morphology and the histochemistry resembled resting zones of normal growth-plate cartilage. Those de novo cartilage discs, which had been embedded in gelled Type I collagen, retained their morphology and could be easily manipulated. On the other hand, Type II collagen and a polyuronic acid gauze (Surgicel) were not satisfactory substrates to facilitate subsequent transplantation into growth-plate defects. The use of 5-carboxyfluorescein diacetate succinimidyl ester (CSFE) throughout the cultures of epiphyseal chondrocytes or prolonged incorporation of [3H]-thymidine appeared to label the cells with useful markers for following their fate subsequent to implantation in vivo.

Reimplantation of growth plate chondrocytes into growth plate defects in sheep.

Defects in growth plates due to trauma, infection, or genetic causes can result in bone formation across the defect, bridging the epiphysis and metaphysis, resulting in growth arrest and limb deformation. We have investigated the capacity of implanted chondrocyte cultures to prevent this process. Sheep growth plate chondrocytes were isolated, and after culture at high density produced easily manipulated cartilaginous discs. The tissue was implanted into growth plate defects produced in lambs and the response was assessed histologically. Following implantation, cultures continued to proliferate and maintain a cartilage-like matrix. After 8 to 12 weeks, hypertrophic maturation chondrocyte columnation, and associated endochondral calcification were observed. Culture implantation was always associated with local immune inflammatory reaction, which continued throughout the course of investigation. Cellular survival was variable and resulted in the presence of viable implants as well as residual cartilage matrix devoid of chondrocytes; however, implanted chondrocyte discs always prevented bone bridge formation. These findings encourage the expectation that cultured chondrocytes may provide a useful replacement for the inert interpositional materials currently used in the treatment of growth arrest. The potential of this technique for growth plate replacement, however, requires a more predictable rate of implant survival. The likely reasons for implant loss are discussed.

Herpes simplex oesophagitis in young children.

Herpes simplex oesophagitis is usually associated with debilitated, traumatized or immunologically-compromised hosts. We report here two cases of severe self-limiting oesophagitis in immunologically competent young children that were caused by herpes simplex type 1. This diagnosis should be considered in the differential diagnosis of acute severe pain on swallowing in children for whom oral and pharyngeal pathology have been excluded.

Successful restoration of immunity in the DiGeorge syndrome with fetal thymic epithelial transplant.

A 13-month-old girl presented with right upper lobe pneumonia and hypocalcaemic seizures: investigations showed hypoparathyroidism and impaired cell-mediated immune responses. Other features of the DiGeorge syndrome included hypertelorism, short philtrum of the lip, right-sided aortic arch, and aberrant origin of the left subclavian artery. Successful restoration of the immunodeficiency was achieved by transplantation of fetal thymic epithelium.

Concomitant IgA nephropathy and cyclical neutropaenia.

A case of concomitant cyclical neutropaenia and IgA nephropathy, a previously undescribed combination is reported. The patient has recurrent aphthous ulceration, and haematuria occurs with these episodes. The diagnosis of cyclical neutropaenia was based on the clinical features and serial peripheral blood studies, and a renal biopsy studied by light, electron and immunofluorescence microscopy in conjunction with the clinical features established the diagnosis of IgA nephropathy. Elevation of serum immunoglobulin, with a disproportionate elevation of IgA was found. The features of this case emphasise the importance of infection as an initiating event in the pathogenesis of IgA nephropathy, and they provide further evidence for the formation of poorly soluble immune complexes as a likely pathogenetic mechanism.