When a new agent is introduced into therapeutics it is important to obtain reliable comparison with existing drugs. Examination of the published reports on guanethidine, methyldopa, and bethanidine provides only an approximate estimate of their comparative merits. Most reports indicate that about 70% of patients achieve reasonable control of their blood pressure with each drug. However, the conditions of the trials varied in many respects, such as levels of blood pressure accepted as good and fair control, the severity of the hypertension in the patients treated, and the clinic routine. In addition, it is difficult to obtain a clear idea of the acceptability of these drugs by patients and of the incidence of side-effects. It was with these factors in mind that, following our initial studies with bethanidine (Johnston, Prichard, andRosenheim, 1962, 1964), we designed a formal trial to compare bethanidine with the established drugs guanethidine and methyldopa.Patients.-Details of the 30 patient-volunteers completing the trial are summarized in Table I; four of the original 34 patients were withdrawn (see below). The patients were selected solely by the criteria that it was thought necessary to treat them with potent hypotensive drugs and that they were able to attend regularly. All except one patient were on potent drugs before the trial-14 on bethanidine, 11 on guanethidine, and 4 on methyldopa. Method Summary of TrialA within-patient comparison was designed in which each patient received bethanidine, guanethidine, and methyldopa. These drugs were prepared in identical capsules and were given in random order, the randomization being stratified according to the treatment the patient was receiving before the trial.Patients were seen at two-weekly intervals during the trial (except for the intrusion of their holidays) under After careful consideration it was not thought desirable for physician A to be " blind." Safe and reasonably rapid adjustment of the dose was essential in order to avoid exposing the patients to unnecessary risk, and as the duration of action of the drugs varies different dose schedules have to be followed. The final decision on instructions to adjust the dose had to be tempered with the knowledge of any side-effects being experienced, most notably symptoms of postural hypotension. In addition, the drugs have several characteristic side-effects which would have permitted physician A in many instances to know which drug was being used.Previous to the " period of assessment " (see below) on each of the three drugs there was a " run-in period." The run-in period was to enable the dose of each drug to be adjusted to obtain the optimal therapeutic effect. The run-in before the first drugs also served to familiarize the patients with clinic procedure, to ensure that they understood the " weekly symptom record sheet" (see below) which they kept, and, lastly, it went some way to ensure that the greater part of the hypotensive effect of increased interest by the physician became stabilized before the tr...

BICALJOUR direct contact between erythrocytes and damaged blood vessels may be a factor in the production of burr cells (Brain et al., 1962). Burr cells were present in all cases that we examined.The peripheral blood film in our patients is therefore in many ways similar to that seen after removal of the spleen. In two patients the level of Howell-Jolly bodies was greater than that said to occur after splenectomy (0.3 % of erythrocytes) and was closer to the higher values (3.9-5.3 % of erythrocytes) which Fraser et al. reported in three cases of splenic atrophy associated with steatorrhoea.The significance of these findings, we believe, is twofold. Firstly, the sequelae of Thorotrast characteristically occur after a long latent period-of the order of 20 years or more-and most patients are unaware that the injection has been made. In the absence of a history of splenectomy previous Thorotrast administration may be suspected when the peripheral blood film shows the changes usually associated with removal of the spleen. This is particularly so when haematological examination is otherwise normal.Secondly, these changes may be indicative of a progressive loss of splenic function in patients exposed to Thorotrast. After intravascular injection the particles of thorium are phagocytosed by reticuloendothelial cells and are deposited mainly in the spleen and liver, and to a lesser extent in the bone marrow. Fig. 2 shows the appearances of heavy deposits of thorium in the spleen of a 33-year-old woman who at the age of 13 had 20 ml. of Thorotrast injected into the left carotid artery.Attempts to estimate dosage to the spleen from the radioactive material deposited there are for technical reasons extremely difficult, but the dosage has been calculated by Rundo (1955) to be in the region of 1,100-1,300 rep' of a-rays and 130-150 rep of a-rays 20 years after an injection of 20 ml. of Thorotrast. As a result of this irradiation, and the interstitial fibrosis which follows the deposition of thorium in tissues, it is not unreasonable to postulate that over the years there will be a progressive loss of splenic function in these patients, and that this will underlie the peripheral blood changes we have described. The careful study and follow-up of such cases may therefore provide useful information regarding the effects of the loss of splenic function and its possible role in some of the sequelae of Thorotrast administration. SummaryThirty-five persons who had received intra-arterial Thorotrast 11 or more years previously were examined. A consistent finding in films of peripheral blood was a disturbance of red cell morphology and the presence of Howell-Jolly bodies. In the absence of splenectomy, and when haematological examination is otherwise normal, such findings are extremely rare. It is thought likely that a progressive loss of splenic function has occurred in these patients as a result of irradiation and that this has caused the peripheral blood changes which we have described. More refined studies of splenic function i...

, CM Vajdic 5 and CAST study group 6 Population-based evidence on second cancer risk following autologous haematopoietic SCT (HCT) is lacking. We quantified second cancer risk for a national, population-based cohort of adult Australians receiving autologous HCT for cancer and notified to the Australasian Bone Marrow Transplant Recipient Registry 1992Registry -2007. Cancer diagnoses and deaths were ascertained by linkage with the Australian Cancer Database and National Death Index. Standardized incidence ratios (SIRs) were calculated and Cox regression models were used to estimate within-cohort risk factors treating death as a competing risk. During a median 2.5 years follow-up, second cancer risk was modestly increased compared with the general population (SIR 1.4, 95% confidence interval 1.2-1.6); significantly elevated risk was also observed for AML/myelodysplastic syndrome (SIR ¼ 20.6), melanoma (SIR ¼ 2.6) and non-Hodgkin lymphoma (SIR ¼ 3.3). Recipients at elevated risk of any second cancer included males, and those transplanted at a younger age, in an earlier HCT era, or for lymphoma or testicular cancer. Male sex, older age (445 years) and history of relapse after HCT predicted melanoma risk. Transplantation for Hodgkin lymphoma and older age were associated with lung cancer risk. Second malignancies are an important late effect and these results inform and emphasize the need for cancer surveillance in autologous HCT survivors.Bone Marrow Transplantation (2014) 49, 691-698; doi:10.1038/bmt.2014.13; published online 17 February 2014Keywords: autologous transplantation; outcomes; risk; surveillance INTRODUCTION Autologous haematopoietic SCT (HCT) is increasingly being used in Australia and elsewhere as a therapy for several haematopoietic and solid organ malignancies. 1,2 Life expectancy following HCT has also improved, 3 increasing the number of HCT survivors globally. Characterizing late effects and identifying those at risk will maximize the long-term health of HCT recipients.Second cancers are a recognized late effect of chemo-radiation therapy in general, and in the HCT setting specifically. 4-11 The cumulative incidence of second cancer after autologous HCT may be as high as 29% after 15 years, 11 with the greatest excess risk observed for AML and myelodysplastic syndromes (MDSs). 10,[12][13][14][15] Most prior studies have examined second cancer risk in recipients of allogeneic and autologous HCT, with the largest based on international transplant registry cohorts. 9 Furthermore, most studies ascertained second cancers from hospital records or by self-report, potentially under-estimating risk. There are no population-based estimates of the risk of secondary cancer in adult recipients of autologous HCT. We examined the incidence and risk factors for second cancer in a national, population-based cohort of 7765 adult Australian autologous HCT recipients, 1992HCT recipients, -2007

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We describe a 7 year old