A family survey was conducted among 909 patients with leukaemia of all types, with the purpose of establishing the incidence of further cases of leukaemia among relatives. Among a total of 41,807 relatives 8,349 were deceased, and the cause of death was objectively confirmed in 5,011. 72 patients had one or more relatives with leukaemia. First degree relatives with leukaemia were much more frequent in families of patients with chronic lymphocytic than in those! of patients with chronic granulocytic leukaemia. The incidence of leukaemia among first degree relatives was established to be 2.8-3.0 times, among more distant relatives about 2.3 times, and overall about 2.5 times that expected. This excess is of the order of that observed in relatives of patients with certain solid tumors. Genetic factors may have accounted for much of the excess incidence in chronic lymphocytic and acute leukaemia, but there was little evidence for a genetic background in chronic granulocytic leukaemia. With the possible exception of one family with muitiple cases, a simple Mendelian mechanism did not appear to be involved in the leukaemia families investigated. It appeared more likely that a polygenic mechanism led to a heightened susceptibility to the disease in these families.
707 conl)lying with the above definition, with the exception of a Ilumber in which tiit' thrombocythemia appeared to be a mere transient i ase in tile course of otiler well substantiated (liSeaSeS. A history of hemorrhage was essential for inclusioii. Either thrombocytosis or thrombosis without hemorrhage VdS illsufficient; for example, cases 1 and 2 reported by Fanger et al.'1' were included, while case 3 was excluded because the patient had not i)led. A diagnosis of "essential" or "idiopathic" thrombocythemia was not acceptable for inclusion, unless hemorrhage was also reported. Cases excluded for this reason comprise tilose of Arlotti and et al.54 (case 3) ,N' 1ortensen, Reid,#{176}'Revol#{176} (cases 1 and 2) ,Rowl ands and Vaizey"4 (case 2) ,Schi ipbach and I-lerrmann#{176}
Thirteen cases of leukemia, 12 of them acute, occurred in 3 generations of a family comprising 293 members. Individual cases could not be linked to the possession of any of a range of genetic markers. Cytogenetic studies showed no constitutional chromosome abnormalities. Preliminary results of virologic studies suggested the presence of oncornaviruses in at least 1 leukemic individual in this family. This aggregation of leukemia cases likely resulted from a genetic, probably polygenic, predisposition, in association with the activity of leukemogenic factors whose nature remains to be clearly defined.
In order to define the functional defect in marrow cells in B12 and folate deficiency, ten patients were investigated. Chromosome studies showed alterations similar to those produced experimentally by agents interfering with DNA metabolism. Measurements of the DNA content of individual cells in the resting and synthetic stages of the mitotic cycle suggested arrest of DNA synthesis in a proportion of cells, or alternatively prolongation of the S and G2 phases. It was concluded that in these deficiency states changes in the cellular DNA metabolism may cause disturbances during both the mitotic and intermitotic stages of the cell cycle, and that these may account for the deficient production of the various classes of blood cells.
SYNOPSIS Westergren sedimentation rates were done on 603 healthy blood donors. The results showed an increase in the normal values with age. The normal values found in this series were higher than those generally accepted as normal.The commonly accepted normal values for the Westergren method of determining the sedimentation rate (E.S.R.) are 3-5 mm. in the first hour for males and 7-12 mm. for females (Whitby and Britton, 1963). During routine blood testing we found a number of apparently normal persons whose E.S.R. exceeded these ranges, and in order to assess the significance of this finding, we undertook a survey of the E.S.R. in healthy blood donors. The results showed that the normal E.S.R. is dependent on age as well as sex. METHODSWe used Dawson's (1960) been withdrawn by a vacuum method. Through the intravenous set which had been used for the donation a further 5 ml. of blood was aspirated into an evacuated 5 ml. bijou bottle containing 5 mg. of sequestrene (E.D.T.A.). The bijou bottles were left standing at room temperature for one to three hours and then mixed on a rotary mixer for a minimum of two minutes. Exactly 2 ml. of blood from each sample was then mixed in another bottle with exactly 0 5 ml. of 3 8 % sodium citrate solution, the same rotary mixer being again used for at least two minutes. One standard Westergren pipette was filled from each sample by drawing blood above the zero mark and allowing it to run back to avoid the 'reflux' effect (Alexander, 1953). The tubes were suspended for one hour and read, the reading being corrected for temperature (Manley, 1957). Room temperatures varied from 20 to 24°C. RESULTSA total of 603 unselected blood donors was tested in two series. The first consisted of 182 males and 114 females. These were divided into five age groups: 18-30, 31-40, 41-50, 51-60, and over 60 years. The mean value and standard deviation were calculated for each age group and showed a steady increase with age. In order to check this result a second series of 213 males and 94 females was tested, and similar figures were obtained for the means and standard
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