The instability of chromosomes with breaks induced by X-irradiation led to the proposal that the natural ends of chromosomes are capped by a specialized structure, the telomere. Telomeres prevent end-to-end fusions and exonucleolytic degradation, enable the end of the linear DNA molecule to replicate, and function in cell division. Human telomeric DNA comprises approximately 2-20 kilobases (kb) of the tandemly repeated sequence (TTAGGG)n oriented 5'----3' in towards the end of the chromosome, interspersed with variant repeats in the proximal region. Immediately subtelomeric lie families of unrelated repeat motifs (telomere-associated sequences) whose function, if any, is unknown. In lower eukaryotes the formation and maintenance of telomeres may be mediated enzymatically (by telomerase) or by recombination; in man the mechanisms are poorly understood, although telomerase has been identified in HeLa cells. Here we describe an alpha thalassaemia mutation associated with terminal truncation of the short arm of chromosome 16 (within band 16p13-3) to a site 50 kb distal to the alpha globin genes, and show that (TTAGGG)n has been added directly to the site of the break. The mutation is stably inherited, proving that telomeric DNA alone is sufficient to stabilize the broken chromosome end. This mechanism may occur in any genetic disease associated with chromosome truncation.

The radical treatment of hypernephroma or renal cell carcinoma has been accepted as primarily, if not solely, a surgical problem. Riches (1964) states "whatever ancillary methods are employed the only effective treatment of malignant renal tumours is a surgical removal. In almost every case this implies nephrectomy." This approach is similar to that expressed by Paterson in his book (1963), where these tumours are classified under the heading of "Radiotherapy Usually Contra-indicated'' and qualified by the statement "in this group surgical excision must be selected as the treatment of choice and must expect no help as a curative measure from radiotherapy as a pre-or post-operative procedure". This basic policy is based on a number of factors. Firstly, and of primary importance, is the relative non-responsiveness of these tumours to irradiation. Accepting that radio-sensitivity and radio-resistance are relative terms, the dose of irradiation which needs to be given to eradicate renal cell tumours is of such magnitude that the tolerance of the normal tissues is far exceeded. This poor responsiveness to irradiation is further accentuated by the macroscopic features of many of these tumours which often contain areas of necrosis with associated avascularity and blood cystic spaces ; features which would further lessen the responsiveness of the tumour to ionising irradiation in view of the anoxic tissues present. Further features which suggest that radiotherapy is unlikely to play anything more than a minor part in the treatment of these malignant tumours is the natural history of the lesions with a propensity to invade veins and hence disseminate widely and finally the complementary factor of the large volume of tissue to be irradiated in order to encompass all sites of possible local extension, specifically including the renal bed, para-aortic gland area and surgical scar. Not surprisingly, therefore, the survival rates for renal cell tumours treated by surgery have shown very little improvement over the years with 5-year survival rates in different published series varying from 33 %-48 % (Table I).Three series of cases of hypernephroma have, however, been published in which an attempt was made to improve the results of treatment by the addition of postoperative radiotherapy. Riches, Griffiths and Thackray in 1951, Flocks and Kadesky in 1958and Bratherton in 1964 showed in their respective series that postoperative irradiation did increase the survival rates at the 5-and 10-year periods (Tables 11, I11 and IV).In each of the series definite improvement was noted in survival rates even though the series were not randomised trials. In view, therefore, of these published figures and the noted improvement it was felt that a randomised trial should be undertaken to evaluate the place of radiotherapy given postoperatively on a more accurate basis. This paper is a review and an analysis of the results from this trial undertaken by the combined Urological and Radiotherapy Units at the Newcastle General Hospital from 1961 to...

The results of conventional chemotherapy in adult acute lymphoblastic leukaemia (ALL) have not improved substantially in recent years. The present study is based on a flexible policy of marrow transplantation (allograft and autograft without marrow purging) in first remission compared with a group treated with standard maintenance therapy after a common induction sequence. The actuarial disease free survival (DFS) and actuarial overall survival (OS) at 3 years for autologous marrow grafted patients was 30% and 65% respectively. The allogeneic transplant group had DFS of 30% and OS at 3 years of 38% compared with DFS (12%) and OS (12%) for patients on 6-mercaptopurine and methotrexate maintenance. The actuarial disease free survival calculations include patients on protocol not entering remission, therefore, giving the worst possible result. We conclude that high dose chemo/radiotherapy with autologous marrow rescue in first remission followed by no maintenance provides better results in terms of overall survival and quality of life than standard ALL maintenance in adult patients. Results for allogeneic transplant in ALL are less good in terms of duration and quality of survival and the majority of deaths are related to causes other than leukaemic relapse.

No abstract

No abstract

No abstract

No abstract

A controlled trial was planned in order to assess the value of postoperative radiotherapy in the treatment of hypernephromata. Crude survival figures, covering 3–12 years following treatment, revealed that those cases treated by surgery only did better than those treated by combined surgery and irradiation, although the results are not statistically significant. Analysis over the first 5 years revealed that the greatest differences in survival between the 2 groups occurred in the first 12 months postoperatively. Radiotherapy did not influence the incidence of local recurrence or distant metastases. However, a considerable number of cases receiving radiotherapy died from co‐incidental causes including radiation liver damage. Those tumors with histologic evidence of venous involvement showed no improvement in survival despite radiotherapy. Other factors associated with tumor prognosis—grade, capsular involvement, and node metastases—demonstrated no advantage in terms of survival for cases having radiotherapy. No correlation could be obtained between histologic grading and prognosis in a small number of cases. Definite evidence of liver damage was obtained in patients with right‐sided lesions as a result of radiotherapy and assessed by biochemical liver function tests and isotope scans. No difference between the 2 sides was noted in relation to side effects during treatment.