1. The present study is an attempt to analyse and apportion significance to the role of inductive mechanisms in bone transplantation.

2. The experimental model used in the present work is that of the composite homograftautograft of cancellous bone previously described (Burwell 1964a).

3. Iliac bone was removed from hooded rats and washed free from its marrow. The bone was then treated by various physical and chemical methods (some of which have been used by other workers to prepare bank bone), namely freezing (-20 degrees Centigrade, -79 degrees Centigrade, -196 degrees Centigrade); freeze-drying (without sterilisation, sterilisation with high energy radiation, sterilisation with ß-propiolactone); decalcification (with E.D.T.A.); irradiation (in the frozen state at a dose of 4 million rads); boiling in water; immersion in merthiolate solution; extraction of organic components with ethylenediamine: and calcining at 660 degrees Centigrade. The treated bone was then impregnated with fresh autologous marrow procured from the femoral shaft of the Wistar rat into which the treated composite graft was to be implanted. The grafts were inserted intramuscularly and removed for study after two, six and twelve weeks.

4. After fixation, serial sectioning and staining, each graft was examined microscopically, and the proportion of new bone/grafted bone scored using an arbitrary scale (0-4). The mean score (and the standard error of the mean score) was then plotted for each treated composite graft and also for several types of fresh cancellous bone grafts.

5. It was found (Fig. 2) that the various treated composite grafts formed a spectrum of bone-forming capacities–the maximum scores being attained by the frozen and freeze-dried composite grafts, the lowest scores by the "deproteinised" composite grafts.

6. The reasons for these differences are discussed. It is concluded that cancellous bone, after transplantation, has the property to induce and promote osteogenesis in marrow; moreover, that this property is contained in the organic components of bone.

7. From the standpoint of inductive mechanisms, cancellous bone treated by freezing or freeze-drying seems to be the most suitable devitalised bone for grafting purposes; bone which has been boiled or merthiolated less suitable; and "deproteinised" bone the least suitable.

8. Freeze-dried bone sterilised physically (by high energy radiation) or chemically (by ß-propiolactone) did not form significantly less new bone than did freeze-dried bone which had not been sterilised.

9. Remodelling mechanisms in bone transplantation are briefly discussed and attention drawn to the deficiencies of present knowledge. The quantitative studies of other workers have indicated that freeze-dried bone may be more rapidly remodelled than is frozen bone.

10. The importance of fresh red marrow in promoting osteogenesis in bone transplantation and in the healing of certain fractures, is emphasised. It seems likely that the interrelationship of bone and marrow revealed by experiment has wider significance not only in health and in response to injury but also in causation of certain idiopathic bone disorders.

1. The effects of the insertion of pieces of fresh cancellous bone into the subcutaneous tissues of the ear upon lymph nodes and spleens have been investigated in seventy rabbits.

2. The main immunological response is found to occur in the first regional nodes draining the sites of insertion of homografts of bone, which show a considerable increase in weight compared with nodes draining autografts of bone.

3. An increased number of large and medium lymphoid cells occurs principally in the first regional node of the homografted animals, as Scothorne and McGregor (1955) observed using skin as the homografted tissue.

4. The large and medium lymphoid cell response is found in both the cortex and the medulla of the lymph nodes. In the cortex a sectoral distribution of the cellular response is observed and the name reactive cortex is given to these sectors. Evidence is presented to show that the sectoral pattern of reactivity is probably determined by the localised entry into the node of iso-antigens through lymphatic vessels draining the bed of the graft.

5. We have made a quantitative analysis of the large and medium lymphoid cell response in the reactive parts of the diffuse lymphoid tissue of the cortex. The mean maximal large and medium lymphoid cell response occurs five days after the insertion of bone homografts.

6. The origin and fate of the large and medium lymphoid cells and their role in the production of antibodies is reviewed in the light of recent work.

7. A correlation is made between the maximal production of large and medium lymphoid cells in the first regional lymph node, the invasion of the graft bed with small lymphocytes and the inhibition of new bone formation in the homografts.

1. An immunological examination of the sera of thirty rabbits which had received primary and secondary homografts of cancellous bone into a subcutaneous site did not reveal the presence of circulating precipitins, haemagglutinins or passive haemagglutinins. These findings are consistent with the observations of Bonfiglio and his colleagues (1955).

2. Electrophoretic examination of the serum of four rabbits receiving primary and secondary homografts of bone into an intramuscular site did not reveal any change in the serum protein fractions.

3. A search for auto-antibodies produced by primary and secondary autografts of cancellous bone was unsuccessful in fifteen rabbits.

4. The multiple injections of saline extracts of bone into four rabbits did not evoke the production of demonstrable circulating antibodies, results which are in accord with the findings of Bonfiglio and colleagues (1955) and Curtiss and colleagues (1959).

5. For the first time the production of classical antibodies in response to injections of extracts of heterologous bone has been recorded. The repeated injections of a saline extract of rabbit bone intraperitoneally into ten mice produced demonstrable precipitins and passive haemagglutinins both to protein and polysaccharide fractions present in the bone extracts.

6. Knowledge concerning the production of humoral antibodies to transplants and extracts of bone has been reviewed.

1. This is a preliminary report of an attempt to determine an objective reference point or "point of motion" during flexion and extension of the lumbar spine.

2. The method described uses superimposition of lateral radiographs taken in flexion and extension with the patient standing.

3. In seventy-eight radiographically normal subjects with no symptoms a "point of motion" was determined for each of the lowest three disc levels. At each level these points clustered within a specific zone approximately 2·5 centimetres square. Sixty-four per cent fell within a square centimetre.

4. In a comparative study of twenty-four patients with confirmed pathology, the "point of motion" fell outside the larger zone at the level of pathological change in 65 per cent of the disc levels.

5. The determination of the "point of motion" is a special technique for studying spinal motion. Its role as a diagnostic and prognostic aid in assessing patients with back pain is the subject of continuing study.

1. The rates of vascularisation in 119 autogenous, homogenous and heterogenous bone grafts, placed in the femoral medullary cavity and under the renal capsule of rabbits, were studied.

2. Substantial differences have been found in the speed of vascular penetration and arrangement among autografts, homografts and heterografts : penetration of the heterogenous implant was six or more times slower. Moreover, large areas of the homografts and heterografts were often totally excluded from the circulation for as long as the research was continued (up to three months). Revascularisation of the cortical bone was slower and less profuse than in cancellous bone, keeping always the same respective proportion between the three types of bone we have described. The results on the kidney were much less constant, and I attribute this to the vascular peculiarities of the bed.

3. Vascular patterns peculiar to the time of implantation and type of graft are described.

4. Suggestive, even if not totally convincing, evidence was found of recanalisation of old vessels inside the graft by advancing vessels from the bed.

5. There is striking correlation between the rate of vascular penetration of the bone implants and their ultimate "take" or incorporation in the bed.

1 . Current theories of the etiology of chondromalacia patellae do not explain satisfactorily either its great frequency or its common site of origin on the medial patellar facet.

2. The etiology can be more logically explained by the presence of a ridge on the upper anterior border of the cartilage of the medial femoral condyle, in most knees. This ridge, consisting of cartilage, or cartilage and bone, varies considerably in height and, in normal knee joint movement, causes considerable friction on the medial patellar facet.

3. The degenerative changes were found to be greater in the presence of the larger ridges, and–because of longer wear and tear–in the older patients.

4. This study indicates that chondromalacia was more severe in women than in men, and in patients overweight. Although the activity of the individual and the power of the quadriceps mechanism must play an extremely important part in this condition, it was not possible to assess this.

5. Two factors previously considered to be important in the etiology of this condition, namely, the length of the patellar tendon and Wiberg's Type III patellar shape, have not been confirmed in this study.

6. Resulting from the present investigation certain precautions are suggested in rehabilitation after operations on the knee, and a surgical method for discouraging the progress of this common, and sometimes disabling, condition has been devised.

1. Surveys of a working community, of a group of elderly people, and of an urban population show an incidence of Dupuytren's contracture among men varying from 0·1 per cent in the age group fifteen to twenty-four, to 18·1 per cent in those aged seventy-five and over; and among women from 0·5 per cent in the age group forty-five to fifty-four, to 9 per cent over seventy-five. It is estimated that in the population aged fifteen and over in Lancashire and Cheshire there will be 4·2 per cent of the men and 1·4 per cent of the women with some degree of palmar contracture.

2. There appears to be no relationship between the type of occupation and the incidence or severity of contracture in men, except that among those engaged in light manual work the proportion of mildly affected hands is higher, and of bilateral contracture lower, than among either non-manual or heavy manual workers.

3. Evidence is provided that rheumatoid arthritis, past polyarthritis, osteoarthritis, cervical spondylosis and Paget's disease occur no more often in those with Dupuytren's contracture than in other members of the community.

4. Examination of the patients in an epileptic colony confirms a strong association between Dupuytren's contracture and epilepsy. Knuckle-pads, plantar nodules and periarthritis of the shoulder are all more frequent in epileptic than in non-epileptic patients with Dupuytren's contracture. Epileptics also show a higher proportion with bilateral contractures and a greater tendency to a symmetrical pattern of contracture in the two hands. A strong constitutional factor, probably genetic, thus operates in persons with both diseases.

Nevertheless, the frequency of a positive family history of contracture is lower in the epileptic cases, and reasons for this are discussed.

5. From the limited material available in the literature there would appear to be an inverse relationship between the population of certain countries and the prevalence in them of Dupuytren's contracture. The possible significance of this is briefly discussed.

Disc degeneration starts as an avascular necrosis. In the lower lumbar area the discs deteriorate early because of mechanical stresses. During certain early periods of degenerative changes a mechanical disorder between the annulus and the posterior longitudinal ligament may cause tiredness and pain. When the disc is completely degenerated and has lost its physical properties backache disappears.

Results are given of a study of four cases of osteogenesis imperfecta using biophysical methods comprising microradiography, microscopy using polarised light, and x-ray diffraction. Rebuilding of bone tissue was infrequent in the material studied and has been shown to occur in an abnormal manner. The mineralisation of the bone is more uniform than is found in normal bone. The collagen has an abnormal organisation and is sparse. The ultrastructure of bone salts and their orientation are as in normal bone.

1. Histochemical studies have been made of the distribution of alkaline phosphatase, glycogen and acid mucopolysaccharides in normal growing bones (mice, rats and men) and also in forty cases of pathological bone processes (neoplastic and dystrophic).

2. The study of normal material confirmed that alkaline phosphatase is plentiful in calcification of cartilage and even more plentiful in bone formation (whether enchondral or direct).

3. It was observed that glycogen increased in the cartilage areas about to be calcified, and that it disappeared in those calcified. It seemed that osteoblasts did not always contain glycogen.

4. In the pathological material (tumours and dystrophic processes) there was great phosphatase activity in the osteogenic areas and also in the cartilage about to be calcified. Whereas glycogen was plentiful in some cases of neoplastic or reactive osteogenesis, it was absent from others.

5. In every area of normal or pathological ossification, the presence of phosphatase seems to be a rule; glycogen is often but not always present.

6. It appears that alkaline phosphatase plays an important role in the formation of the protein matrix of bone, but is not associated with the elaboration of the mucoprotein cartilage matrix.

We believe it is premature to draw any definite conclusion on the behaviour and role of the metachromatic substances in the processes of calcification and ossification.

The histochemical study of alkaline phosphatase has shown that this is a valuable method in the detection of reactionary or pathological osteogenic processes which in some cases are difficult to demonstrate with the usual histological methods.

Blood flow in intact tendons in dogs was measured using 57Co-labelled microspheres and compared with the simultaneous clearance of a diffusible radionuclide, 85Sr, by the same tendons. Clearance was significantly greater than flow in all tendons, indicating that diffusion from surrounding tissues may be important in the nutrition of normal tendons.

1. The family history of, and associated congenital abnormalities in, patients with talipes equinovarus, talipes calcaneo-valgus and metatarsus varus living in Devonshire has been studied.

2. The chances of any individual having one of these deformities is approximately one per 1,000 in each case.

3. If one child in a family has the deformity, the chances of a second having it are one in thirty-five for talipes equinovarus and one in twenty for talipes calcaneo-valgus and metatarsus varus.

4. The male relatives of the female patients with talipes equinovarus are at particular risk.

5. It is suggested that the cause of club foot is partly genetic and partly environmental, from a factor acting on the foetus in the uterus.

6. The classification of associated congenital abnormalities leads to the suggestion that the genetic factor in talipes equinovarus and talipes calcaneo-valgus relates to defective formation of connective tissue.

1. The appearance of decalcified bone matrix in the electron microscope is described.

2. In the matrix two types of collagen fibril have been distinguished. Differences observed are in solubility, x-ray diffraction pattern and appearance. In infant bone the form which appears as fine fibrils predominates. In adult bone the form which appears as tubular fibrils of larger diameter predominates.

3. In bones from elderly subjects the chemical reaction employed to convert collagen into eucollagen sometimes hydrolyses fatty acid esters, and lines due to the free fatty acid are found on the x-ray diffraction patterns of the insoluble residue after citrate extraction.

4. In ancient bones and fossils the stable tubular form of collagen survives, but not the fine fibrils.

5. When decalcified, the matrix in osteoporotic bones loses its architecture and fibrillar form. Under conditions in which only a small fraction is dissolved from normal bone most of the collagen in osteoporotic bone disperses in citric acid. The insoluble residue then gives a modified x-ray diffraction pattern.

6. Evidence has been produced to suggest that the immediate cause of many forms of osteoporosis is some local factor affecting the osteocytes, rather than a general chemical effect.

Sarcoma complicating Paget's disease is uncommon; ninety-five cases have been collected and seven further cases are now reported. Sarcoma probably complicates less than 2 per cent of all cases of Paget's disease. There is a relatively high incidence in males, especially in the sixth decade, whereas bone sarcoma over the age of fifty years without osteitis deformans is rare. Injury is prominent in the history of many cases.

Comparison of Paget's sarcoma, "ordinary" bone sarcoma and the bones affected by uncomplicated osteitis deformans reveals some important differences. As to the type of tumour, osteogenic sarcoma is the commonest, but fibrosarcoma and round-cell sarcoma are also frequent.

The serum phosphatase is a most useful prognostic guide in a disease with a generally poor prognosis. Magnesium metabolism in relation to bone sarcoma requires further study.

Prophvlaxis is based on a clinical suspicion of this complication in Paget's disease, and measures are outlined which may be of assistance.

Sarcoma in Paget's bone is highly lethal, but Nature in striking down these old people may have provided us with facts which will ultimately solve problems common to all sarcomas of bone.