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Biomedical subjects

J Peto

Publications and source records attributed to J Peto.

At least 91 records · Page 5Linked to original sources
PubMed1982

Relative contributions of insulin deficiency and insulin resistance in maturity-onset diabetes.

The effects of raised insulin resistance and decreased beta-cell function on basal plasma glucose and insulin concentrations have been estimated by means of a mathematical model which uses the available data on control of glucose and insulin flux. The model shows that near-normal basal plasma insulin levels could be maintained by means of basal hyperglycaemia when beta-cell function is deficient. The hyperglycaemia does not become pronounced until more than 80% of beta-cell function has been lost. However, when only 5-10% of beta-cell remains, plasma insulin levels fall in spite of hyperglycaemic stimulation. Conversely, raised insulin resistance in the absence of decreased beta-cell function induces only a small rise in basal plasma glucose concentrations, which stimulates a compensatory increase in basal plasma insulin concentrations from a normal beta-cell capacity. However, if the beta-cell dysfunction is sufficient to induce a basal plasma glucose concentration of 5-6 mmol/l, a slight rise in insulin resistance causes pronounced basal hyperglycaemia.

Adipose Tissue↗
PubMed1982

Mesothelioma mortality in asbestos workers: implications for models of carcinogenesis and risk assessment.

Mesothelioma death rates in asbestos workers appear to be proportional to the 3rd or 4th power of time from first exposure under a wide range of conditions of exposure for both pleural and peritoneal tumours, though the peritoneal:pleural ratio depends on fibre dimension and type. Age at first exposure has little or no influence, however, which supports the "multi-stage" model of carcinogenesis under which the increase in most cancer incidence rates with age is due to a constant incidence of genetic or epigenetic accidents, rather than to progressive generalized changes in regulatory or immune function. These relationships provide a simple basis for risk assessment, and support the suggestion that mesotheliomas may constitute a high proportion of cancer deaths resulting from early exposure to asbestos.

Adolescent↗
PubMed1981

Acute lymphoblastic leukaemia: four-year survivals old and new.

Two groups of four-year survivors with acute lymphoblastic leukaemia (ALL) are compared: an 'old' series consisting of 83 patients diagnosed before 1968, and a 'new' series of 366 patients included in Medial Research Council trials (UKALL I-III) and diagnosed in 1970-4. Both series differed significantly from a group of ALL patients who survived less than four years in having lower total leucocyte and blast-cell counts at diagnosis, but the new series did not show the significant differences in organ involvement and platelet count seen in the old series. In both series, girls were more likely than boys to survive for four years and less likely to have relapsed meanwhile; in the new series, relapse rates were also lower for girls than for boys after four years, and subsequent survival was significantly better. There was no difference between the two series in survival rates of those patients who had relapsed before reaching four years. A much higher proportion of the new series, however, had reached four years without prior relapse, and these had a more favourable subsequent survival than the corresponding group of the old series. About 90% of patients achieving four years' continuous complete remission on these UKALL regimes seem likely to survive for 10 years.

Adolescent↗
PubMed1981

Immunologically defined subclasses of acute lymphoblastic leukaemia in children: their relationship to presentation features and prognosis.

Leukaemic cells from 542 patients under 21 years of age with a diagnosis of acute lymphoblastic leukaemia (ALL) were typed with immunological cell surface markers between June 1975 and December 1979; 379 of these patients entered into the trials up until December 1978 have been followed for more than 1 year. They were divided into four subgroups: common (c) ALL, T (thymic) ALL, 'null' (or 'unclassified') ALL and a rare lymphoma/leukaemia type B-ALL. A T-cell phenotype was found more frequently in boys and was usually but not invariably associated with a high white cell count at presentation. A mediastinal thymic mass was present in 53% of T-ALL patients but was not observed in any unequivocal not-T ALL. Clinical prognosis differed substantially between the three major phenotypic classes, remission induction rate and remission duration being lowest in T-ALL, better in 'null' ALL, and highest in cALL (P trend less than 0 . 0001; P = 0 . 0002 for comparison of cALL versus T-ALL). There was a much higher incidence of CNS involvement in the T-ALL group than in the cALL group or 'null' All group and although this was strongly correlated with WBC count it was also significantly associated with T-ALL independent of WBC count. Overall in this series and also within the major cALL subclass there is a strong correlation between high WBC count and poor clinical response (remission induction and duration). When the three major immunological subclasses are adjusted for WBC count the prognostic correlation of antigenic phenotype is reduced and statistically insignificant. It is suggested that immunological (and enzymatic) phenotype of ALL subclasses may not be an independent correlate of prognosis but nevertheless is linked to other cell differentiation features, especially growth rate and sites of clonal expansion (e.g. marrow versus thymus), which critically influence the size of the clonogenic leukaemic population and its associated evolutionary status with the respect to drug resistant mutants at the time of diagnosis and introduction of therapy.

Adolescent↗
PubMed1980

The incidence of pleural mesothelioma in chrysotile asbestos textile workers.

Analysis of the incidence of pleural mesothelioma in asbestos textile workers in relation to age, time since first exposure, intensity of exposure and period of observation indicates that age per se is largely irrelevant; that is, the incidence 30 years after first exposure appears to be much the same irrespective of age at first exposure. This has been shown to be true in animal experiments and has been suggested on theoretical grounds for certain human cancers; it explains the evolution of lung cancer rates in relation to changing smoking habits but has not been demonstrated directly by human data. These results also suggest that mesothelioma incidence may not have been much underestimated in the past, which would imply that the recent marked increase in recorded rates is largely real and not merely a diagnostic artefact. The risk does not appear to have been much higher among men who were initially very heavily exposed. One possible explanation of this surprising observation is that chrysotile is eliminated, or ceases to be biologically active, more quickly than other types of asbestos.

Adult↗
PubMed1980

Lung cancer mortality in relation to measured dust levels in an asbestos textile factory.

A cohort of 255 men who entered this factory since the beginning of 1951, when routine dust sampling weas initiated, have been followed up to the end of 1978. Eight (1.62 expected) died of lung cancer over 20 years after first exposure (P less than 0.001). Earlier estimates of dust levels hve been revised to correspond to modern counting methods, and the average cumulative exposure of this cohort is now estimated to have been 200-300 fibres/ml-years. No deaths have yet been attributed to asbestosis, but a separate study of this group has reported that 10 of these men have been certified as asbestotic. An earlier analysis of lung cancer, mesothelioma and asbestosis incidence in men employed prior to 1951 suggested a dose-response relationship for lung cancer in relation to static sampler dust measurements that was probably approximately correct, but it is not clear whether personal sampling wound give similar results.

Aged↗
PubMed1979

Collaborative United Kingdom-Australasian study of cancer in patients treated with immunosuppressive drugs.

A collaborative study including centres in the United Kingdom, Australia, and New Zealand was instituted in 1970 to determine the incidence of cancer in patients treated for at least three months with azathioprine, cyclophosphamide, or chlorambucil. Follow-up of 3823 renal transplant recipients showed an almost 60-fold increase of non-Hodgkin's lymphoma together with an excess of squamous-cell skin cancer and mesenchymal tumours. A series of 1349 patients without transplants showed an excess of the same tumours, though to a less extent. These preliminary findings provide no clear evidence that immunosuppressive drugs produce the increased risk of most of the common cancers that might be expected from the simplest interpretation of impaired "immunosurveillance."

Adolescent↗
PubMed1979

Cyclic oscillations of basal plasma glucose and insulin concentrations in human beings.

In a study of whether oscillations in plasma glucose and insulin occur in human beings, plasma samples were taken at one-minute intervals from 10 normal subjects for periods lasting between one and two hours. In five subjects the basal plasma insulin concentrations cycled regularly, with a mean period of 13 minutes and mean amplitude of 1.6 mU per liter (11.5 pmol per liter). A concurrent plasma glucose cycle was demonstrated, with a mean amplitude (after averaging to minimize random error) of 0.05 mmol per liter (1 mg per decliter). The average plasma glucose cycle was two minutes in advance of the plasma insulin. In the subjects with less regular plasma insulin cycles, a similar plasma glucose rise was demonstrated two minutes before the insulin rise. These phase relations are compatible with the presence of a negative-feedback loop between the liver and pancreatic beta cells that regulates both basal plasma insulin and glucose concentrations, although the cyclic beta-cell secretion could be independent of plasma glucose.

Adult↗
PubMed1979

Insulin deficiency and insulin resistance interaction in diabetes: estimation of their relative contribution by feedback analysis from basal plasma insulin and glucose concentrations.

The liver and beta cells function in a negative feedback loop, which appears to have a predominant role in regulating both the basal plasma glucose and insulin concentrations. The degree of basal hyperglycemia in diabetes probably provides a bioassay of both the effect of a reduction in insulin secretory capacity and the degree of insulin resistance. A mathematic model of the interaction of insulin deficiency and insulin resistance has been constructed, based on the known response characteristics of the beta cells to glucose, and of plasma glucose and insulin control of hepatic and peripherpal glucose flux. The degree to which beta cell deficiency increases basal plasma glucose reflects the hyperbolic shape of the normal insulin secretory response to different glucose concentrations. The height of basal plasma insulin is a function of the degree of insulin resistance. From the basal plasma insulin and glucose concentrations, the model provides an estimate of the degree to which both beta cell deficiency and insulin resistance contribute to diabetes. The predictions arising from the model are in accord with experimental data in man and in animals. In normal-weight diabetics who do not have increased insulin resistance, the model predicts that more than 85% of beta cell function has to be lost for the basal plasma glucose to rise to 6 mmol/liter, but a further 5%--10% loss increases the basal plasma glucose to over 10 mmol/liter. In a third of a consecutive series of 65 newly presenting, uncomplicated diabetics, both normal weight and obese, the analysis from the model suggested that insulin resistance, rather than beta cell deficit, was the predominant feature.

Blood Glucose↗
PubMed1978

MVPP chemotherapy regimen for advanced Hodgkin's disease.

During January 1968 to December 1972, 133 patients with advanced Hodgkin's disease (HD) were admitted to hospital for combination chemotherapy with mustine, vinblastine, procarbazine, and prednisolone (MVPP regimen). Remission rates were 76% among 49 untreated patients and 90% among 42 patients who had relapsed after radiotherapy. The corresponding five-year survival rates were 65% and 86% respectively. Provided the observed yearly mortality (6%) remains unchanged 75% of patients who had previously received no treatment or irradiation and achieved remission are expected to continue in first remission after five years. Forty-two patients had received prior chemotherapy. They had lower remission and five-year survival rates (40% and 33% respectively), and fewer than half of those achieving remission were still in first remission after five years. There were several reasons for the poor prognosis in this group, including advanced-stage disease (stage IVB), age over 40, and achievement of remission.Chemotherapy was administered on an outpatient basis. Haematological toxicity and immediate drug-related side effects were similar to those of other regimens but there was no appreciable neurotoxicity. Most deaths were due to either HD itself or complications of advanced disease. Five malignancies other than HD occurred in patients who had received both single-agent chemotherapy and radiotherapy before MVPP chemotherapy. Two patients developed osteonecrosis of the femoral heads.Combination chemotherapy has a profound effect on the prognosis of advanced HD. The MVPP regimen yields results comparable to those of other regimens but with perhaps less toxicity.

Adolescent↗