Long-term follow-up of adult AML patients.
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Adolescent↗
Biomedical subjects
M M Roberts
Publications and source records attributed to M M Roberts.
Hyponatremia in rats induces downregulation of vasopressin synthesis.
Hyponatremia due to inappropriate secretion of vasopressin is a common disorder in human pathophysiology, but vasopressin synthesis during hypoosmolality has not been investigated. We used a new method to quantitate synthesis of vasopressin in rats after 3, 7, and 14 d of hyponatremia induced by administering dDAVP (a vasopressin agonist) and a liquid diet. Vasopressin synthesis was completely turned off by 7 d. Vasopressin mRNA levels in the hypothalamus paralleled the reduction in synthesis and were reduced to levels of only 10-15% of the content in control rats. When hyponatremia was corrected by withdrawal of dDAVP, vasopressin mRNA slowly returned to normal over 7 d. The observation that vasopressin synthesis can be so completely turned off leads to several conclusions: under normal physiological conditions the neurohypophysis is chronically upregulated; there must be an osmotic threshold for initiation of vasopressin synthesis (and release); the large store of hormone in the posterior pituitary is essential for vasopressin to be available during times of decreased synthesis; and, finally, some nonosmolar stimulus for synthesis must be present during clinical disorders when vasopressin is secreted (and synthesized) despite hypoosmolality.
Animals↗
Single high doses of cyclophosphamide enable the collection of high numbers of hemopoietic stem cells from the peripheral blood.
We used single high doses of cyclophosphamide (4 g/m2) to produce rebound increases in peripheral blood (PB) stem cells (PBSC) during recovery from myelosuppression, enabling their collection by apheresis for later autotransplantation. Thirty-three courses of cyclophosphamide were given to 30 patients with malignant lymphoma, multiple myeloma, or solid tumors. The neutrophil count was less than 0.5 x 10(9)/liter for a mean of 6.9 days (median 7 days), and fever occurred in 17 of 33 courses. Positive blood cultures occurred in two patients, one of whom died. The mean peak level of PB granulocyte-macrophage colony-forming units (CFU-GM) was 1517 x 10(3)/liter (median 2447 x 10(3)/liter), a 14-fold increase above the mean in normal subjects. The peak occurred at a mean of 16.6 days (median 16 days) after cyclophosphamide, generally coinciding with the time to reach 1.0 x 10(9) neutrophils per liter. Normal or minimally involved bone marrow and a rapid rise in leukocyte count during recovery were independent variables correlated to the peak of the rebound increase in PB CFU-GM levels. Previous chemotherapy and the duration of neutropenia were additional independent variables in the group with peak PB CFU-GM levels of greater than 1000 x 10(3)/liter. The mean total CFU-GM collected after a mean of five aphereses was 43.8 x 10(4)/kg body weight (BW) (median 35.5 x 10(4)/kg BW), significantly correlated with the mononuclear cell yield. We conclude that single 4 g/m2 doses of cyclophosphamide effectively produce high levels of PBSC, particularly but not exclusively in patients with normal or minimally involved bone marrow and who have not had intensive recent chemotherapy.
Adult↗
An unusual pattern of hemopoietic reconstitution in patients with acute myeloid leukemia transplanted with autologous recovery phase peripheral blood.
Fourteen patients with acute myeloid leukemia (AML) were autotransplanted with peripheral blood cells collected during early remission. Seven were autotransplanted in first relapse and seven in first remission. They received a median of 3.3 X 10(8) nucleated cells/kg body weight (BW) and 92 X 10(4) myeloid progenitor cell (CFU-GM) per kg BW. Rapid hemopoietic reconstitution (HR) occurred in all patients with median time to reach normal neutrophil and platelet counts 13 and 18 days post re-infusion respectively. However, in three patients neutrophil counts fell to less than 1.0 x 10(9)/l and in seven patients platelet counts fell to less than 25 x 10(9)/l between 26 and 40 days post-transplant (trough count). In all but two patients who received the lowest CFU-GM dose the counts returned to normal or near normal levels (steady count). There were significant correlations between the CFU-GM dose and the trough and the steady platelet counts (p = 0.04 and 0.01 respectively). Patients receiving more than 50 x 10(4) CFU-GM/kg BW had higher steady neutrophil and platelet counts (p = 0.011 and 0.033 respectively) although some patients receiving greater than 50 x 10(4) CFU-GM/kg still experienced thrombocytopenia during the second month post graft. There was no significant correlation between the nucleated cell dose and HR. The cause of the fall in platelet and neutrophil counts in the second month post graft is not clear but is probably a reflection of a proliferative defect in the recovery phase stem cells in AML.
Adolescent↗
Breast cancer stage, social class and the impact of screening.
Two studies were carried out to examine socio-economic factors in breast cancer: a random sample of all new cases in Edinburgh in 1979 was reviewed, and the control population of the Edinburgh randomized trial of breast screening was used to determine stage and survival in relation to social class. Small area statistics from census data were used as measures of social class, the method being now well accepted. More than one-third of women still present with obviously advanced or metastatic breast cancer, but both studies showed this has no association with socio-economic status. Late stage at presentation is a serious problem, and although mass screening is likely to cause an improvement in those who are screened, it cannot in those who do not attend for screening. As attendance is related to social class, less affluent women are less likely to benefit and will continue to be diagnosed with advanced disease.
Adult↗
Breast screening: time for a rethink?
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Breast Neoplasms↗
The preparation and biochemical characterization of intact capsids of equine infectious anemia virus.
Capsids of equine infectious anemia virus have been isolated as cone-shaped particles 60 x 120 nm in size. Detergent treatment of whole virus followed by two cycles of rate-zonal centrifugation in Ficoll produces these capsids in a yield of approximately 10%. The major protein components are the gag-encoded p11 nucleocapsid protein and p26 capsid protein, which are present in equimolar amounts. Substantial cleavage of p11 to p6 and p4 can be observed under conditions where the viral protease packaged in the capsid is enzymatically active.
Capsid↗
Randomisation by cluster and the problem of social class bias.
For randomised population trials the unit of randomisation is normally the individual person. In some situations, however, investigators take other groups as basic unit and one such design is cluster randomisation. Considerable attention has been given to this design recently in statistical and epidemiological literature. The Edinburgh randomised trial of breast cancer screening is an example which takes general practices as clusters of patients. The experience of this trial is reported here. Mortality from all causes, cardiovascular disease and lung cancer over the first 5 year period of follow up are examined. We found that spurious mortality differences were present in the analyses, which do not allow for socio-economic status. From examination of methods of adjusting for this, we conclude that allowance can be made at the analysis stage, and it is intended that this approach will be adopted when breast cancer mortality is analysed in the Edinburgh trial. Nevertheless, we recommend that for future studies with outcome related to socio-economic status, randomisations which use this design be stratified by socio-economic criteria where this is feasible.
Bias↗
Total translation of vasopressin and oxytocin in neurohypophysis of rats.
There is a paucity of information about total translation rate of vasopressin and oxytocin. Because the site of synthesis of the neurohypophysial hormones is anatomically separate from the site of storage, we were able to measure total translation by blocking transport of newly synthesized hormone and measuring accumulation in the areas of synthesis in the hypothalamus. Colchicine administered into the third ventricle in doses as low as 3.5 micrograms/rat blocked transport for 18 h. The linear increase in vasopressin and oxytocin content over 18 h indicated a stable rate of synthesis, which was 1.2 and 1.9 pmol/h for vasopressin and 1.4-2.5 pmol/h for oxytocin. The molar correlation for synthesis of total neurophysin to total hormone was 1.16. Infusion of oxytocin and vasopressin into rats indicated that this level of synthesis of hormone was essential under steady-state conditions to maintain plasma levels in the low physiological range of approximately 3 pg/ml for oxytocin and 1 pg/ml for vasopressin. The data on total synthesis of the neurohypophysial hormones provide a reference for studies in which physiological replacement is required and also provide the technique and base-line data to determine how translation of vasopressin and oxytocin is regulated when neurohypophysial function is altered.
Animals↗
The optimization of collection of peripheral blood stem cells for autotransplantation in acute myeloid leukaemia.
Between November 1982 and November 1986 31 patients with acute myeloid leukaemia underwent peripheral blood stem cell apheresis during haemopoietic regeneration following induction chemotherapy. A retrospective analysis of the factors affecting the efficacy of stem cell harvest and of the clinical outcome of these patients was performed. The mean number of myeloid progenitor cells (CFU-GM) collected was significantly higher in the complete remission group (n = 22) than in the partial remission group (n = 9). Fifty x 10(4) CFU-GM/kg body weight or more, which produced rapid, complete and sustained haemopoietic reconstitution after autografting in our patients, were collected from six of nine patients who underwent three or four 7-litre aphereses over 5-7 days using a lymphocyte collection procedure on the Fenwal CS3000 [Protocol B] but only from two of 12 patients who underwent three or four 5-litre aphereses over 3-5 days using the Aminco Celltrifuge [Protocol A] (p less than 0.05). No adverse effects on the rates of neutrophil, platelet and lymphocyte recovery after induction chemotherapy or on long-term disease-free survival for patients who achieved a complete remission could be attributed to apheresis when compared with a historical control group of 39 patients who achieved complete remission following the same induction chemotherapy but did not undergo apheresis. We conclude that sufficient numbers of peripheral blood stem cells to produce safe and rapid haemopoietic reconstitution can be collected from most patients who achieve complete remission using apheresis Protocol B without impairment of haemopoietic recovery or adversely affecting the length of complete remission.
Antineoplastic Combined Chemotherapy Protocols↗
Consolidation therapy without maintenance for acute non-lymphoblastic leukaemia.
The most effective therapy to prolong remission and to increase cure rates in patients with acute non-lymphoblastic leukaemia is uncertain, and approaches vary from one course of consolidation to two years of maintenance and intensification therapy. We report the results of brief intensive therapy with daunorubicin, cytosine arabinoside and thioguanine, and no maintenance therapy, in 72 patients with a minimum follow-up period of two years. The complete remission rate was 67%, the median duration of remission was 11 months, and 23% of patients whose leukaemias went into remission, have remained in remission for three years and longer. These results are equivalent to those that have been reported with long-term chemotherapy.
Actuarial Analysis↗
Expression of a 150-kD cell surface antigen identified by monoclonal antibody YB5.B8 is associated with poor prognosis in acute non-lymphoblastic leukaemia.
Peripheral blood specimens, obtained from 71 patients with newly-diagnosed acute non-lymphoblastic leukaemia (ANLL) prior to the initiation of therapy, were assayed for the presence of a myeloid leukaemia-associated cell surface antigen identified by monoclonal antibody YB5.B8. The antibody bound to cells from 22 patients, and these patients had a poorer overall survival rate than those whose cells failed to bind the antibody (p less than 0.025). Fifty patients were treated with daunorubicin/cytosine arabinoside/6-thioguanine (DAT) according to a standard protocol and survived at least to the end of the induction phase (7 days). Of the 34 patients whose cells were YB5.B8 negative, 28 obtained a complete remission. In contrast, only four of the 16 patients whose cells expressed YB5.B8 antigen obtained complete remission (p less than 0.001). Expression of the YB5.B8 antigen in ANLL appears to be a strong prognostic indicator which is independent of other known prognostic factors such as patient age, leucocyte count and pre-existing hematopoietic abnormality.
Adolescent↗
Bone marrow biopsy during induction chemotherapy for acute myeloid leukaemia identifies only 50% of patients with resistant disease.
A study was carried out to determine whether bone marrow biopsy performed on day 6 of induction therapy for acute myeloid leukaemia (AML) can identify those patients with resistant disease who would need an intensification of the first course of induction. Bone marrow biopsies were performed on day 6 of induction chemotherapy in 44 patients with AML treated with daunorubicin, cytosine arabinoside and thioguanine. Biopsies were assessed for blast count, trephine cellularity and leukaemic index. Discrimination between patients who went on to achieve remission and those with resistant disease was best achieved using the reduction in bone marrow cellularity from pretreatment marrow to day-6 marrow. However, this discriminator identified only 50% of the patients with resistant disease and included 13% of patients who achieved remission with the first course of chemotherapy. The other parameters of response were even less effective at discriminating between chemotherapy-resistant and chemotherapy-responsive disease.
Antineoplastic Combined Chemotherapy Protocols↗
Attenders and non-attenders at a breast screening clinic: a comparative study.
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Breast Neoplasms↗
Use of risk factors to allocate schedules for breast cancer screening.
In an effort to reduce the cost of breast cancer screening several studies have explored the possibility of using risk factors to select a high-risk group of women and then restrict screening to that group. The results of these studies have been almost entirely negative and so it is not possible at present to classify any woman as at such low risk that she need not be screened. Nevertheless it is well known that some groups of women can be identified as being at higher risk than the general population. In this study it is assumed that each woman will be offered one screen at which risk factor information will be collected. The usual screening policy is then one of uniform intervention in which the interval to the next screen is the same for all women: the interval that is currently recommended in the UK is three years. An alternative is a risk strategy in which the time to the next screen depends on the woman's risk status; thus the total number of screens available to the population are distributed according to risk status. Using data from the Edinburgh randomised trial of breast cancer screening these policies have been compared. It is estimated that the proportion of cases detected by screening in the three years following the completion of the initial screening round could be raised from 60% to 67% by adopting a risk strategy. Lead time benefits are also quantified as are the comparisons for an established screening programme.
Age Factors↗
Cervical screening at a breast screening clinic.
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Adult↗
Pityriasis versicolor and sunscreens containing coconut oil.
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Coconut Oil↗
Consultations for breast disease in general practice and hospital referral patterns.
As part of the evaluation of a health education campaign about breast disease, consultations for breast problems were monitored in five general practices over an 18-month period in Edinburgh. No increase was found as a result of the campaign, nor was there any increase in the number of biopsies performed. On average, each GP saw 13 women with breast problems each year, a rate of 1.6 per cent; 29 per cent were referred to hospital, regardless of their age. The most common presenting symptom was pain (47 per cent), with 35 per cent complaining of a lump. The reasons for hospital referral are discussed. It is suggested that GPs may refer too many young women to a specialist clinic, although this may be inevitable.
Adult↗